Possible New Drugs for Alzheimer’s Disease Treatment-Part V of a XXVIII Part Article on AD

(Editor's Note: For those of you who have included this article as one of your favorite sites, please note that we have started a separate article for Alzheimer's Disease clinical trials which used to be part of this article. To go to that article please go to: See: See: Alzheimer's Disease-Part XX-Clinical Trials


(7/8/24)- The FDA approved the sale of the Alzheimer’s drug donanemab, which be sold under the brand name Kisunla, by Eli Lilly & Co, The drug has been shown to have significant risks, including brain swelling and bleeding in the brain.

The other drug recently approved by the agency in the battle against AD, which is manufactured by Eisai and Biogen,is given every 2 weeks while donanemab is given every month.

The list price for Kisunla is $32,000 for a one year cost for the drug..Lequembi costs $26,000per year, but is not stopped after amyloid plaque is removed. Treatment with Kisula is expected to stop after the amyloid plaque is removed.

There is no treatment for AD that stop or even reverse memory loss or decrease in cognitive ability.

(6/12/23)- The Centers for Medicare and Medicaid Services (CMS)announced it would cover Biogen and Eisai’s Alzheimer’s drug L Leqembi if the drug wins full approval of the agency by July 6.

This was the deadline date set when the drug was conditionally approved in January.

Eli Lilly said in May it would seek full approval of its drug donanemab, which had also conditional approval.

(1/9/23)- The Federal Drug Administration (FDA) has given conditional early approval for sale of the Alzheimer’s disease drug lecanemab, which we discussed in our items dated 12/4/22 and 9/30/22 below . Biogen Inc. and Eisai Co. are the 2 companies that developed the drug. These were the 2 companies behind the Alzheimer’s controversial drug Adulhelm.

The companies plan to commercially sell the drug under the brand name of Leqembi starting January 23^rd for $26,500 for a year’s treatment of the average patient.

The drug will be infused twice a month at an outpatient clinical site or at a hospital.

The drug has the risk of brain swelling and bleeding, particularly in the first few months of administration.

(12/4/22)- As a follow-up to our item dated 9/30/22, the deadline for the FDA to approve lecanemab is January 6. 12.6% of the study’s patients had brain swelling, vs 1.7% in the placebo group, according to researchers who presented the data at the Clinical Trials on Alzheimer’s disease.

There were 2 deaths reported in the data through October in the group taking the drug and 1 death among the placebo group.

(9/30/22)- Biogen and Eisai, the pharmaceutical companies that gave us the AD drug Aduhelm, as written in several of the items below, announced that their latest drug to fight Alzheimer’s had slowed the rate of cognitive decline in a large late-stage clinical study.

The drug, lecanemab, which is administered intravenously resulted in a 27% decline over 18 months in cognitive ability compared with the group that received the placebo. There were 1,800 patients with mild cognitive impairment were involved in the study.

Some medical experts said the drug’s ability to slow cognitive impairment was 0.45 on 18-point-scale was modest at best.

Eisai has already applied for accelerated approval of the drug to the FDA, with the agency’s approval of the drug could happen in early January.

(5/5/22)-Biogen Inc. announced that it was effectively abandoning the sale of its Alzheimer’s drug Aduhelm and replace its chief executive and dismiss the high-ranking executive who promoted the drug.

The drug had brought in only$2.8 million in revenue in the first quarter of this year, after generating only $3 million in revenue in 2021.

Individuals who want to use the drug will must pay$28,200 or join in a clinical study of the drug.

(4/11/22)-Medicare officials finalized their decision in connection with Biogen Inc’s Alzheimer drug Aduhelm, denying coverage for payment to Medicare beneficiaries, except if the drug is used in a clinical trial. Biogen official said they would appeal the ruling.

(1/15/21)- Medicare officials said they would limit the coverage for Biogen Inc’s Alzheimer drug Aduhelm only if the patient is in a clinical trial supported by the National Institute of Health and is in the early stage of the disease.

Medicare would also require that the patients have lab tests confirming that their brain has accumulated amyloid.

A final decision is expected in April following an additional 30-day comment period.

(12/22/21)-In an attempt to revitalize the lagging sales of its Alzheimer’s drug Aduhelm, Biogen Inc. announced that it was cutting the cost of the treatment with the drug to $28, 200 from $56,000, when the drug gained FFDA approval back in June.

Several health insurers refused to pay for the drug, since it did now show efficacy, and many medical organizations, such as the Mt. Sinai Hospital Complex, the Mayo Clinic and the Department of Veterans Affairs.

(11/19/21)-Biogen Inc. announced that a panel of drug reviewers for the European Union had indicated that its newly approved. Alzheimer’s drug Aduhelm was unlikely to be approved there.

The committee of experts in the European Union that advises the European Medical Agency had issued a “negative trend vote”, a preliminary signal that the drug will not be approved. The panel will formalize its vote next month.

cause of the death. Doctors have reported other adverse effects to the data base.

Brain swelling was a common side effect shown during the drug’s clinical trial period, which is thought to be ARIA-E. About 80% of those cases were resolved.

(10/28/21)- Eli Lilly & Co. said it began filing a rolling submission of its study data to The Food and Drug Administration for its experimental Alzheimer’s disease drug donanemab. The company said that it expects to complete its application in the next few months., with the hope that the agency approves its application in the latter part of 2022

Donanemab targets amyloid build up on the brain that forms plaque in, which the company believes causes Alzheimer’s. It is administered intravenously, and 270 patients are involved in the study, which hopefully will grow to 1500 patients, with results expected in 2023.

For additional info on this drug please see our item dated 4/26/21 below.

(8/29/21)-The Centers for Medicare and Medicaid Services (CMS) began a payment review for the Alzheimer’s drug Aduhelm in January and is now tsking public comments as to whether or not it should pay for the drug’s usage. The estimated cost for the infused drug is about $56,000.

The agency is expected to issue its ruling in April 2022.

(8/17/21)-The Veterans Administration has decided that it would not add Biogen Inc.’s Alzheimer drug Aduhelm to its formulary because of the risk of causing serious side effects...in addition there is lack of convincing evidence of the drug’s ability to improve cognitive ability.

(7/18/21)- Mount Sinai Health System in New York and Providence in Renton Washington have now also announced that they would not administer Aduhelm to Alzheimer patient in their system.

In the case of Mount Sinai, it announced that it would wait for the results of the investigation as to whether or not employees of the FDA were influenced by Biogen to arrive at its dcision’

(7/16/21)- The Cleveland Clinic announced that it would not administer Aduhelm to any of its Alzheimer patients.

”Based on the current data regarding its safety and efficacy , we have decided not to carry aducanumab at this time”

(7/14/21)- Medicare officials have begun their review of Aduhelm to set the agencies parameters for coverage of the drug under the program. The review of an analysis of the clinical studies, as well as checking over the 2 public hearings held by the FDA’s advisory and full committee hearings held in connection with Biogen and Esai’s data on the trials.

The review will then set the terms for the national coverage of the drug by Medicare and Medicaid patients. The determination iis expected to take up to 6 months.

(7/11/21)- The Food and Drug Administration (F. D.A.) narrowed the prescription instruction for usage of Aduhelm, so that only those in early stages of the disease be given the drug. Anyone already on the drug would be an exception and allowed to be continued to use it.

The agency also announced that it would begin an investigation of the possible conflict of interest that might have affected the decision of certain members who voted for its approval.

(6/28/21)- Medical experts vary greatly the estimated cost to Medicare for Aduhelm and donanemab, with the range being between $5.8 billion to $39 billion a year.

Tricia Neuman, executive director of the Kaiser Family Foundation stated: “Its unfathomable.” “These are crazy number.”

(6/25/21)- As a follow-up to our item dated 4/26/21. Eli Lilly & Co. said it would seek approval from the Food and Drug Administration (FDA) to market its Alzheimer’s disease drug donanemab. As pointed out in that item, the clinical trial involved only 257 patients.

The drug has not proven to be effective in reversing the course oof the disease/

(6/9/21)-The Food and Drug Administration (FDA) overruled its advisory panel recommendation and voted to grant accelerated emergency approval to Biogen Inc. and its partner Esai Co. for the sale of their Alzheimer’s disease drug aducanumab. The FDA will require the company to conduct a post approval study to confirm the drug’s benefit.

The drug will be sold under the name Aduhelm and will cost about $56,000. It will require monthly infusions at a clinic. Patients will require monitoring with MRIs to guard against small brain bleeds. In one of the 2 studies of the drug in clinical trials 41% of the patients showed small brain bleeding.

We have written many items in this column in which the drug failed to meet its desired result in treating Alzheimer’s patients. The most recent of these items is dated 4/2 6/21 below. The drug clearly did not help patients with severe or moderate cognitive impairment.

There were 121,499 deaths from AD in the U. S. in 2019. The agency last approved a new Alzheimer drug in 2003. Prior approvals were for Namenda and Aricept, neither of which is a cure for the disease. Approval was granted for Aduhelm because it did show some reduction in the buildup of amyloid plaque on the brain.

We at therubins do understand what a devastating disease Alzheimer’s is, but feel that the advisory panel’s denial of its approval should have been upheld by the agency. Further proof of its efficacy need be shown before approval could be granted.

(4/26/21)- As a follow-to our item on Elly Lilly & Co.’s possible new drug donanemab for the treatment of Alzheimer’, the Friday edition of the New York Times has an article entitled “They’re In a Clinical Trial for Alzheimer’s To Keep Hope Alive” that the company is looking for possible subjects to be part of a 1,500 person group to evaluate the effectiveness of the drug.

The earlier study that we discussed consisted of only 257 patients that lasted 76 weeks that did slow the onset of the disease.

Lilly has hired Global Alzheimer’s Platform Foundation, a network of clinical trial sites, to try and find potential patients. To qualify the potential patient can’t have advanced Alzheimer’s nor early onset of the disease.

(3/16/21)- As a follow up to our item dated 1/21/21 below, Eli Lilly & Co. announced details of its Alzheimer’s drug of the International Conference on Alzheimer’s and Parkinson diseases and published them in the New England Journal of Medicine. The drug, donanemab is in clinical trial Phase 2, and involved 250 patients in the U. S. and Canada.

Donanemab is an intravenous infusion that targets amyloid plaques in the brain. Early results show it does the cognitive and functional decline in the early stages of Alzheimer patients over the study period of 18 months.

(2/5/21)- Updating our item dated 11/9/20 below, Biogen Inc., and its partner Eisai Co., said their Alzheimer’s drug will undergo an additional 3 months of review by the Food and Drug Administration of its denial of approval of aducanumab. The advisory panel will therefore take up the matter again on June 7.

Biogen said it had submitted additional analyses and clinical data to the FDA in response to an information request for additional information from the agency.

(1/12/21)- Eli Lilly said a trial of its Alzheimer’s drug donanemab showed it slowed by about a third the rate of decline in a combined measure of cognition and function in early-stage victims of the disease.

Lilly said the mid-stage trial of 272 patients met its main goal of showing a statistically significant change in clinical decline over 18 months.

We at therubins would like to emphasize the fact that the clinical trial involved only 272 patients, and that in turn means, it has a long way to go before the drug will be accepted by the FDA.

(11/9/20)- The FDA’s Priority Review Committee, in a seven hour virtual meeting Friday, soundly rejected Biogen’s application for approval of its Alzheimer’s disease drug aducanumab to become the first new drug to fight the disease in almost 20 years. The vote was 10-1 against approval stating it was not “reasonable” to consider the research “primary evidence of effectiveness”.

It is estimated that almost 6 million Americans suffer from Alzheimer’s with the worldwide total estimated to be 20 million.

For more background on aducanumab please see our items below.

(11/6/20)- As noted in our item dated 9/30/20 below the Drug Administration’s Priority Review Committee is holding its hearing today to consider Biogen’s application for approval of aducanumab for the treatment of Alzheimer’s disease. The advisory panel will vote on whether the drug is effective in treating the disease.

The FDA does not have to concur with the advisory committee’s recommendation, but usually does so

(9/30/20)- The Food and Drug Administration’s Priority Review Committee will hold a hearing on November 6 to consider Biogen’s application for approval of aducanumab for the treatment of Alzheimer’s disease. The application is based on the 2^nd clinical trial results of patients as we discussed in our item dated 8/28/20 below.

(8/28/20)- In our items dated 12/7/2019 and 10/21/2019 we discussed the results of Biogen Inc., and Eisai Co.’s Alzheimer drug aducanumab. The companies felt that the results of the 2^nd clinical trial were promising enough for them to pursue their application to have it approved by the Food and Drug Administration’s (FDA) for sale as a treatment for the disease.

The companies announced that the agency would act on its application by March 7. As noted in the item dated 10/21/2019, the companies said that they would terminate the trials even though the 2^nd clinical trial showed some positive results in treating the disease.

There are an estimated 5 million Americans currently living with the disease.

(7/31/20)- A newly developed test for Alzheimer’s has diagnosed the disease as accurately as methods that are far more expensive, scientists reported at a meeting of the Alzheimer’s Association International Conference. The report was published in the American Journal of the Medical Association.

The test determined whether people with dementia had Alzheimer’s instead of another condition. The test measured a form of the tau protein found in tangles that spread throughout the brain in Alzheimer’s patients. The study consisted of 1,402 people from 3 different groups in Sweden, Columbia and the United States.

The test was 96% accurate in determining whether people with dementia had Alzheimer’s rather than other neurodegenerative disorders.

Dr. Oskar Hanson, a senior author of the study and a professor of clinical memory research at Lund University in Sweden, and Dr. Kal Blennow presented their findings at the conference.

Nearly 6 million Americans and about 30 million people worldwide have the disease.

(2/11/20)- The search for a drug to treat Alzheimer’s disease continues to run into failures. The latest clinical trial results from a trial started in 2012 involved patients with a particular gene mutation that greatly increased their risk for developing Alzheimer’s, even for those as young as in their early 30s.

Some of the 194 participants were given Eli Lilly & Co.’s solanezumab, while others were given Roche Holdings AG’s gantenerumab, with a third group receiving a placebo. Neither drug was able to slow cognitive memory decline as measured by several tests of thinking and memory, according to a spokesman for Washington University’s School of Medicine.

Last year, there were 405 drugs being studied for AD, up from 381 the prior year, according to a report from Informa UK Ltd.

(12/7/19)- Additional details about aducanumab were provided by Biogen Inc. later in the day Thursday at the Clinical Trials on Alzheimer’s disease conference in San Diego.

At least 15.6% of patients receiving the drug experienced brain bleeding and at least 16.8% experienced brain swelling. The clinical trials for the drug were terminated in March because there was less than a 205 chance that the drug would succeed in slowing cognitive decline

Biogen stated that it would seek FDA approval to sell the drug based on the successful study.

(12/6/19)- As noted in our item dated (10/24/19) below, Biogen Inc. and Eisai Co, presented additional data on their Alzheimer’s disease Phase 3 clinical drug trial of aducanumab at an Alzheimer meeting in San Diego on Thursday.

In its presentation, Biogen said that in one of its two trials, the rate of decline among AD patients on a high dosage of the drug was 23% slower than patients on a placebo, based on one measure. In the other study patients on the drug declined 2% faster than those on the placebo.

More details on the data will be forthcoming later from Biogen.

(10/24/19)- In our item dated 3/24/19 and 3/23/15 below we noted that Biogen Inc. and Eisai Co announced that they would abandon pursuing their Alzheimer’s autoimmunological drug aducanumab. Biogen has now announced however, that after taking a closer look at the results of the late-stage clinical data, it had determined that high dosages of the drug would work in improving the memory of patients in that grouping.

After taking a second look at the data the company had conversations with FDA officials, so that the Cambridge, Mass. biotechnical company will seek regulatory approval for the drug early next year.

(3/24/19)- Biogen Inc. and Eisai Co. said they would terminate two late-stage studies of the Alzheimer’s disease drug, since it failed to help patients.

The drug Aducanumab thus is being added to the long list of Beta amyloid drugs that have failed in the battle against AD. Please see our item dated 3/23/15 re Aducanumab.

(2/23/17)- Unfortunately, Merck & Co. announced that its Alzheimer’s disease drug verubecestat had failed to achieve its goal, and thus joined Eli Lilly’s solanezumab in the battle against the disease. Please see our item dated 11/25/16 below for further info on solanezumab.

Lilly took a $150 million charge on its fourth quarter earnings report because of its failure.

The Alzheimer’s Association estimates that 5.4 million Americans currently have the disease, and that it costs Medicare and Medicaid spent about $160 billion last year on caring for patients with the illness.

Many medical experts have come to the conclusion that dealing with the buildup of amyloid plaque on the brain is the wrong approach to coming up with a drug that will lead to success in treating Alzheimer’s disease.

(12/6/16)- Biogen Idec. is hopeful that its Alzheimer’s disease drug aducanumab can reverse the failures in the fight against the disease when it announces the results of its experimental drug in December. Eli Lilly & Co.’s recent failure of its Alzheimer drug solanezumab,, as we wrote about in our item dated 11/25/16 is still fresh in our memory. Please see our item dated 3/23/15 below in connect with adaucnuamab

Biogen is being sued by Forward Pharma, a small Danish biotech company for patent infringement in connection with the drug. A final ruling in that case is expected in the first quarter of 2017.

(11/25/16)- Unfortunately, Eli Lilly & Co. has reported that the trial of its Alzheimer’s drug solanezumab on 2,100 patients with mild dementia had not been successful in halting the progression of the disease. As we noted in our items dated 10/11/12 and 8/30/12 below, clinical trials of the drug were also unsuccessful, but a small subset of patients had shown some cognitive improvement.

These failures throw into doubt the theory that preventing or removing the build-up of amyloid plaque on the brain was the answer in the battle against the disease.

(12/26/15)- The new budget package signed into law by President Obama recently boosted Alzheimer’s research spending to $936 million, an increase of $350 million, according to the National Institute on Aging.

The disease affects over 5 million Americans, and Democratic presidential nominee Hillary Clinton has outlined her plan, which would set aside $2 billion a year through a big increase in government research spending for the disease.

(9/4/15)- Novartis AG, the Swiss pharmaceutical company, and Amgen Inc., the U.S. biotech outfit will team up to help Novartis to expand its Alzheimer’s disease drug pipeline. Novartis will pay Amgen an upfront fee, followed by milestone payments in a deal centered on so-called BACE inhibitors. The drug class hopes to prevent the build-up of amyloid plaque on the brain, which many scientists believe is a precursor of the disease.

Amgen would pay the majority of the research-and development costs for the program “for an agreed upon period”, after which the companies would split costs and profits equally.

(5/24/15)- As a follow up to our item dated 12/18/14 below, the U.S. Circuit Court of Appeals for the Second Circuit in New York ruled that Actavis cannot withdraw its best-selling Alzheimer’s disease drug Namenda IR in favor of its newer drug Namenda XR. New York’s attorney general Eric Schneiderman has sued to block the switch.

A three-judge panel upheld U.S. Federal Court Judge Robert W. Sweet for the Southern District of New York issuance of a preliminary injunction that would prevent Actavis Inc. from discontinuing manufacturing its older version of its Alzheimer’s drug Namenda.

The two drugs had the same active ingredient, memantime, but the older drug’s patent was due to expire. The newer drug, Namenda is taken once a day, versus the twice a day routine for the older drug.

(3/23/15)- The early results of a small clinical study of an experimental drug called aducanumb slowed the decline in mental function of Alzheimer disease. The drug in question has been developed by Biogen Idec., but there was a high incidence of a particular side effect that might make it dangerous to use in high dosages. In light of all the recent failures that have occurred in the battle against Alzheimer’s, even a small victory means there is a ray of hope.

Other drugs have previously looked hopeful in their Phase 1 trials, only to be proven non-effective in their latter trials.

Aducanumab, which until now was known as BIIB037, is designed to get rid of amyloid plaque in the brain. The patients enrolled in the small study were in the early phase of Alzheimer’s, and the plaque in the brain was diagnosed by a new imaging technique. There is no definitive proof that build-up of amyloid plaque on the brain leads to Alzheimer’s

There were only 166 patients enrolled in the trial. A major negative side effect was a swelling of the brain did occur, known as A.R.I.A.E, with those who got the higher dosage of the drug suffering from the largest enlargement of the brain.

The results were presented in Nice, France, at the International Conference on Alzheimer’s and Parkinson Diseases and Related Neurological Disorders.

(1/15)- - Actavis plc (NYSE: ACT) and Adamas Pharmaceuticals Inc. (NASDAQ: ADMS) announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for Namzaric, a fixed-dose combination (FDC) of memantine hydrochloride extended-release, a NMDA receptor antagonist, and donepezil hydrochloride, an acetylcholinesterase inhibitor. Namzaric was approved for the treatment of moderate to severe dementia of the Alzheimer's type in patients stabilized on memantine hydrochloride and donepezil hydrochloride.

(12/28/14)- U.S. Federal Court Judge Robert W. Sweet for the Southern District of New York has issued a preliminary injunction that would prevent Actavis Inc. from discontinuing manufacturing its older version of its Alzheimer’s drug Namenda.

The old form of Namenda is a tablet that is taken twice a day, but its patent expires in July, 2015. Actavis has a newer form of the drug, which is called Namenda XR, which is in capsule form, and is taken only once-a-day. The patent on the older form of the drug is due to expire shortly.

Actavis obtained Namenda when it bought Forest Laboratories Inc. The drug is known generically as memantine, and its sales exceeded $1.5 billion in Forest’s last year, which ended in March. A month’s supply of the drug costs about $300.

(7/21/14)- )- Roche Holdings AG, the Swiss drug company continued the trend of disappointing Alzheimer’s disease clinical drug test results with its announcement at the Alzheimer’s Association International Conference in Copenhagen that crenezumab failed to slow the progression of the disease.

Dr. Carole Ho, who heads a clinical development group at Genentech, Roche’s subsidiary in California, said the company had not decided whether it would proceed with the additional trials for the drug.

The Phase 2 study involved 431 patients with mild to moderate Alzheimer’s disease. They received a high dose of the drug, a low dose or a placebo.

Crenezumab, which Genetech licensed from AC Immune, a privately held Swiss company, is a type of protein called monoclonal antibody that binds to beta amyloid, so that it can be cleared from the brain. Both Eli Lilly, and the team of Pfizer and Johnson & Johnson had similar type drugs that failed in Phase 3 studies.

(2/15/14)- An article in the New England Journal of Medicine, Jan. 23, Vol. 370, pages 322-333 entitled "Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease" failed to show any positive anti-amyloid-beta effect. Bapineuzumab, a humanized anti–amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease. Please see our item dated 8/30/12 below.

(12/3/13)- Government officials announced a $33.2 million grant as part of its national Alzheimer’s plan that will help finance a clinical trial to test a treatment on people 60 to 75 years of age who have no symptoms of the disease, but do have two copies of a gene known to greatly increase the risk of getting the disease.

The project will be led by Dr. Eric M Reiman and Dr. Pierre N. Tariot of the Banner Alzheimer’s Institute in Phoenix, Az. The clinical trial will take place mostly in the United
States on 650 patients who have two copies of the gene ApoE4.

Studies have shown that more than half the people with two ApoE4 genes will develop Alzheimer’s, compared with about one-fourth of people with one copy and 10 percent

(7/8/13)- FDA has expanded the approved indication for Exelon Patch (rivastigmine transdermal system) to include the treatment of people with severe Alzheimer's disease (AD) with Exelon Patch 13.3mg/24h. Exelon Patch is now the first and only transdermal therapy approved to treat patients with mild, moderate and severe AD

(6/15/13)- The news continues to be bad in the battle to find a drug that helps to alleviate the symptoms of Alzheimer's Disease. Eli Lilly & Co. announced the termination of the Phase II study for its BACE inhibitor (LY2886721) for the treatment of Alzheimer's, citing abnormal liver biochemistry.

As we noted in our item dated 12/14/12, this news comes on top of Lilly's announcement not to submit a Biologic License Application for its AD drug solanezumab.

The company indicated that it would continue to pursue this mechanism as a potential treatment option for the disease. Other BACE inhibitors in development include Merck's MK-8931 and AstraZeneca's AZD3480, both of which are in Phase II trials.

(5/30/13)- Approximately a year ago, the journal Science published an article about bexarotene as a potential Alzheimer's drug -- a significant breakthrough and an important starting point for further Alzheimer's research.

Now other researchers have tested this candidate drug in various Alzheimer's animal test models. Their results were different, as were those of two American study groups. Therefore, they have recommended that bexarotene should not be tested on patients.

(5/9/13)- Another disappointment in the battle to treat Alzheimer's disease came with the announcement from Baxter International that it was halting the clinical trial of its drug Gammagard, because it failed to halt the mental decline caused by the disease in its late stage trial.

Gammagard is an immunoglobulin therapy that did not significantly arrest the decline in either cognitive awareness of daily functioning when compared with the placebo.

The trial involved 390l patients with mild to moderate symptoms of Alzheimer's who were treated for 18 months.

This was the third failure of an Alzheimer's disease drug that was in Phase 3 trial. The others were Eli Lilly & Co.'s solanezumab and Pfizer & Co. and Johnson & Johnson'sbapineuzumab.

(12/14/12)- In a press release dated 12/12/12, Eli Lilly & Co. announced that after meeting with officials from the Food and Drug Administration (FDA), it had decided not to submit a Biologices License Application (BLA) at this time in the United States for its Alzheimers drug Solanezumab.

The company will continue to analyze the data from the two, Phase 3, double blind, placebo-controlled solanezumab EXPEDITION studies.

(10/11/12)-Although two separate clinical trials of Eli Lilly & Co.’s Alzheimer drug solanezumab missed the goal of significantly slowing the progression of Alzheirmer’s disease, the pooled results of the two trials found 34% to 42% less mental decline in mild Alzheimer’s patient compared to those on a placebo treatment for 18 months. For additional information on this matter, please see our item dated 8/30/12 below.

The results of the combined studies were revealed at an American Neurological Association meeting in Boston on October 8. The two studies each had about 1,000 patients, about two-thirds with mild versions of the ailment, and one-third with moderately severe AD from 16 countries. Their average age was 75.

The company stated in August that solanezumab failed to work in the two late-stage drug trials testing its effectiveness in slowing both the erosion of memory and of basic abilities in patients with mild to moderate levels of AD.

(9/12/12)- The US Food and Drug Administration (FDA) has approved a 13.3 mg/24 hour dosage strength of the rivastigmine transdermal system (Exelon, Novartis) for patients with mild to moderate Alzheimer's disease who are experiencing a decline in overall function and cognition.

The rivastigmine patch is already approved at doses of 4.6 mg/24 hours and 9.5 mg/24 hours for the treatment of mild to moderate dementia of the Alzheimer's disease (AD) type, and mild to moderate dementia associated with Parkinson's disease.

(8/30/12)- The battle against finding a cure for Alzheimer's disease suffered another setback when Eli Lilly & Co. announced that its Phase 3 drug solanezumab clinical trials failed to significantly slow cognitive decline versus a placebo in Alzheimer's patients. Please see our earlier item dated 7/30/12 below, where Pfizer halted further trials of its AD drug bapineuzumab.

Both solanezumab and bapineuzumab were aimed at the buildup of a-beta amyloid placque on the brain.

Full results of two of the clinical trials named "Expedition 1" and "Expedition 2" will be revealed at a medical conference in October.

The analysis of the pooled data from the trials did show that solanezumab slowed cognitive decline in patients with mild Alzheimer's.

(7/30/12)- Pfizer & Co. announced that it was halting the clinical trial of its Alzheimer's drug bapineuzumab, since it did not improve cognition or daily functioning of patients compared to a placebo in the Phase III trail. The company did not provide any details, saying they would be presented at a medical meeting in September.

Dr. Reisa Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women's Hospital in Boston, who was one of the principal investigators in the study said: "There was absolutely no evidence at all of a clinical benefit of treatment on either of the primary measures, one cognitive and one functional".

All of the 1,100 American patients in the trial had the ApoE4 gene variant, which is associated with a higher risk of developing Alzheimer's disease. Three other trials are still under way, one involving patients with the gene and two in patients without it. About half the Alzheimer's patient have the gene.

Bapineuzumab is being developed jointly by Pfizer and Johnson & Johnson. Elan, an Irish pharmaceutical company has a financial stake in the drug also. The drug is aimed at clearing beta amyloid or preventing its formation in the brain.

(6/21/12)- Roche Holdings AG, the Swiss drug company, said it would pay AC Immune an undisclosed upfront fee and up to 400 million Swiss francs ($420 million) in additional payments if the partnership yields a successful drug for Alzheimer's disease.

The new treatment aims to attack the disease by blocking a protein in the human body called tau. The two companies are developing another drug discovered by AC Immune, which is aimed at attacking the buildup of amyloid plaque in the brain.

Other companies investing in tau related drugs include Bristol-Myers, Squibb Co, and closely held TauRx Pharammceuticals, based in Singapore.

Last month the US government said it would help fund a $100 million trial of a drug Roche licensed from AC Immune in 2006-crenezumab, which aims to prevent amyloid plaques from forming in the brain.

(1/22/12)- As we noted in our item dated 9/9/08 below, Pfizer & Co. took a long shot in 2008 when it partnered with Medivation Inc., on its Alzheimer's drug Dimebon. This was not a cheap long shot that Pfizer took, since it agreed to pay Medivation $225 million up-front, and up to $500 million more if some milestones were achieved in the development of the drug.

Dimebon was an antihistamine that was a common cold remedy in Russia. Back in 2010 Pfizer and Medivation announced that Dimebon had failed to meet its primary and secondary goals in a phase III trial that evaluated the drug against the workings of a placebo in subjects with mild-to-moderate AD

Recently, the companies announced that they were halting the program for developing the compound, after it failed to meet two primary endpoints in a phase III study evaluating the drug in combination with Aricept in patients with mild-to-moderate AD.

It is estimated that there are 5.3 million people in the United States and 18 million people worldwide suffering from Alzheimer's disease.

(7/22/11)- Unfortunately Eli Lilly & Co.'s Alzheimer's disease compound semagacestat was shown to have a negative effect on patients' cognitive ability, so the clinical trial of the drug had to be discontinued. The safety findings were presented at the Alzheimer's Association International Conference which was held in Paris recently.

Safety data presented at the same conference on a late-stage investigational Alzheimer's treatment called bapineuzumab suggested serious side effects such as brain swelling.

Lilly had announced last August that patients taking the experimental drug in a clinical trial fared worse on cognitive symptoms than those taking a placebo. Those same patients had an increased rate of skin cancer.

Lilly halted the trial and ceased any further trials of the compound, but the company continued to follow the patients in order to provide them with safety monitoring and to try to understand what went wrong.

The new data was a follow-up on the patients 32 weeks after they received the last dose of the drug. The follow-up study failed to show any improvement in the cognitive ability of the patients after the drug was stopped.

Researchers presented results of the Investigation of Transdermal Exelon in Alzheimer's Disease (IDEAL) study at the American Neurological Association (ANA) 131st Annual Meeting. This was a double-blind, placebo-controlled, multi-center trial.

The study compared the efficacy, safety, and tolerability of a once-daily rivastigmine patch with conventional twice-daily rivastigmine capsules and placebo. "This is the first successful attempt to put a cholinesterase inhibitor into a patch formulation and represents an important treatment alternative for patients with Alzheimer's disease," study co-authors Jeffrey L. Cummings, MD, from the University of California, Los Angeles Alzheimer's Disease Center stated about his study.

(9/13/09)- A drug now used to treat cancer may also be able to restore memory deficits in patients with Alzheimer's disease, according to a new study conducted by scientists at Columbia University Medical Center, which appeared in the September issue of the Journal of Alzheimer's Disease: Volume 18:1.

The research was done with mice who are bred to have an equivalent form of Alzheimer's disease. The cancer drug is from a family of compounds called HDAC inhibitors, which increase the DNA's spool acetylation and gene transcription. The drug improved memory performance to the level found in normal mice. Testing of this drug will not begin in humans for three to four years.

(3/15/09)- The following information written by Susan Jeffrey appeared on Medscape Medical News accessed March 13, 2009: March 12, 2009.

"A new product deemed a medical food by the Food and Drug Administration is now available in the United States, the manufacturer, Accera, has announced."

"Known by the brand name Axona, the food targets metabolic deficiencies associated with Alzheimer's disease (AD). It has been shown in a phase 2 clinical trial to improve cognition and memory in patients with mild to moderate disease, a statement from the company notes. Dispensed by prescription, it comes in single-serving packets and is taken once daily mixed with water."

In her article, Susan Jeffrey indicates that "A medical food is an FDA-regulated product, the Accera release states, in a relatively new category of medical protocols defined by Congress as part of the Orphan Drug Act. Medical foods were defined in 1988 as a special category of products intended for the specific dietary management of a disease or condition that has distinctive nutritional requirements, established by medical evaluation. Prior to 1988, the company notes, medical foods were regulated as drugs"

On the Axona web site, this food product is presented this way: "Axona is a medical food intended for the clinical dietary management of the metabolic processes associated with mild to moderate Alzheimer's disease...This medical food product will be administered under physician supervision and dispensed by prescription only. It can be taken safely alone or with other commonly prescribed Alzheimer's disease medications (acetylcholinesterase inhibitors and NMDA receptor antagonists), as no significant interactions have been observed...The most common adverse events were diarrhea, flatulence, and dyspepsia...No significant interactions with commonly prescribed medications for Alzheimer's disease have been observed".

This food product is only obtainable with a physician's prescription. It is to be used in mild to moderate cases of Alzheimer's disease. Note should be made that it has not completed stage three trials and that it is not intended as a cure for Alzheimer's disease. The phase two results were presented at the 2007 Alzheimer's Associaqtion Conference on Prevention of Dementia. The study involved 152 patients in a double-blind, randomized, placebo-controlled trail with probable mild to moderate Alzheimer's disease. This was a company sponsored study. At this time, we have been unable to find any study done to attempt to replicate the results reported.

We do not know of any HMO that will pay for this food product, nor has Medicare/Medicaid approved it. Desperation may drive many families to try this product. We at therubins.com take no stance on its value. Our hope is that further research will clarify its role for some subgroup of Alzheimer's disease patients, so that they can get on with their lives in a fairly normal fashion.

We will bring you more on this food product and others in the Alzheimer's disease pike as it becomes available to us.

Researchers from Nottingham's two universities are joining forces to develop a simple blood test to diagnose Alzheimer's disease.

The £200,000 study, funded by the leading charity the Alzheimer's Research Trust, will aim to find out whether 'biomarkers' in blood could be used to identify someone with Alzheimer's.

A biomarker is a term for something present in the body which can indicate disease, such as a certain protein or molecule. The Nottingham team will be identifying biomarkers by looking at proteins in the blood of Alzheimer's patients compared to a control group of healthy older people.

The researchers at The University of Nottingham hit upon the idea of using biomarkers as a means of diagnosis and will be involved in collecting the samples in conjunction with collaborators in the UK and EU, while the samples will be tested using technology based at Nottingham Trent University.  

(9/9/08)- Pfizer Inc. is really taking a long shot in its attempt to find a drug that deals with Alzheimer's disease. In what could be up to a $750 million gamble, the company is working with Medivation Inc., a tiny San Francisco based biopharmaceutical company, to develop a drug named Dimebon, which is a 25- year old Russian antihistamine drug.

Pfizer said it will pay $225 million, plus additional milestone payment of as much as $500 million for the right to develop and co-market the drug in the U.S, and marketing rights outside the U.S.

In an exceedingly small study of only 183 patients in Russia, the drug seemed to slow the progression of the disease. The Russian study was designed as a mid-stage Phase II trial, but has been accepted as a Phase III " pivotal trial" by the U.S. Food and Drug Administration.

This in effect means that Pfizer needs only to replicate the results in order to file for drug approval. Please keep in mind it is one thing to slow the progression of the disease and an entirely different matter to reverse the damages that the disease causes.

(8/4/08)- As a follow-up to our item dated 7/4/08 below, about Elan Corp. and Wyeth Corp's Alzheimer drug bapineuzumab, results presented at the recent International Conference on Alzheimer's Disease in Chicago showed that patients did not benefit from a higher dose of the drug than a lower dose. People who fared best on the drug were those without the gene variant that supposedly predisposes humans to AD.

On the other hand, Medivation Inc reported at that same conference that its Alzheimer's drug Dimebon seemed to benefit patients with both mild to moderate symptoms of the disease. A previous placebo-controlled 12- month study showed that Dimebon helped improve people in measurements of memory and thinking, activities of daily function and behavior.

The latest data presented at the conference from an open-label extension (doctors and patients know what drug is being administered to them), showed that those benefits continued after six months with no additional side effects.

Though the Dimebon study was a Phase II trial of only 183 patients, the FDA told Medivation earlier this year that it can use the data as one of the two trials required for regulatory approval.

The company is currently enrolling more than 500 patients in a Phase III trial in the U.S., Europe and South America, and expects to file for FDA approval in 2010 if the study is successful..

(7/4/08)- There are more drugs in the neurological-disease pipeline for Alzheimer’s Disease than for any other illness except pain, according to the industry trade group Pharmaceutical Research and Manufacturers of America. The build-up of beta amyloid plaque on the brain is probably the most researched cause for the disease.

Scientists are postulating that if you can remove the amyloid plaque, you can reverse the harmful effect causing the disease. So far, research involving the removal of the plaque on the brain of mice has not shown that it results in improved cognitive behavior.

Elan Corp. of Ireland and Wyeth Corp of Madison, N.J.. announced that the Phase II results of their AD drug bapineuzumab showed some signs of effectiveness in this area. The drug did fail on overall measures of success but showed enough promise so that it will remain in clinical trial testing. The drug helped people who aren't genetically predisposed to developing AD, since these patients showed significant improvement on a number of cognitive tests, and less loss of brain volume.

Those patients carrying the gene associated with higher AD risk demonstrated some benefit on the tests, but not at a statistically significant level.Wyeth and Elan began a 4,100 patient $300 million Phase III trial in December, even before seeing the complete Phase II results of bapineuzumab.

Data from Myriad Genetics Inc.'s key Phase III clinical study of its AD drug Flurizan, which is the largest and longest human trail to date showed that the drug did not improve thinking ability by a statistically significant amount compared with a placebo. Myriad had spent about $200 million on Flurizan, which aims to inhibit enzymes that create amyloid.

The clinical trial of Flurizan showed that the drug did not improve the ability of patients to carry out daily activities. The company said it would discontinue development of the drug.

Eli Lilly & Co. is in a late-stage testing of a drug that works somewhat similarly to Flurizan, by inhibiting an enzyme called gamma secretase. 

Human autopsies have shown that the mere presence of large amounts of amyloid plaque does not always correlate with AD, according to Bruce Miller, clinical director of the University of California at San Francisco Memory and Aging Center.

Please also see our item dated 6/22/08 below.

(6/22/08) Would you bet on a drug that has a thirty percent chance of reaching the market? Apparently, many stock investors had this idea on Tuesday, June 17, when the stock of the pharmaceutical company, Wyeth, rose 4.83 percent on a potential product for treating Alzheimer’s disease. The drug is bapineuzumab, "one of 23 paths that Wyeth is exploring under its so-called war on Alzheimer’s" (NY Times June 18, C2). Phase 3 stage of this drug evaluation started in Dec. 2007. It is a multicentered, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety trial in patients with mild to moderate Alzheimer’s disease who are apolipoprotein E4 non-carriers. The study is expected to be completed in Dec. 2010

For those who would like to enroll in the study, we present the following material:

Inclusion Criteria:
Diagnosis of probable AD
Age from 50 to less than 89
Mini-Mental Status Exam score of 16-26 inclusive
Brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of AD
Stable doses of medications (cholinesterase inhibitors and memantine allowed)
Caregiver able to attend all clinic visits with patient

Exclusion Criteria:
Significant neurological disease other than AD.
Major psychiatric disorder.
Significant systemic illness.
History of stroke or seizure, autoimmune disease, myocardial infarction within the last 2 years.
Smoking greater than 20 cigarettes per day.
Anticonvulsants, anti-Parkinson's, anticoagulant, or narcotic medications.
Prior treatment experimental immunotherapeutics or vaccines for AD.
Women of childbearing potential.
Presence of pacemakers, CSF shunts, or foreign metal objects in the eyes, skin or body.

Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00574132
Telephone- 1 866 446 5463

(4/21/08)- Statins and Alzheimer's disease- Statins burst on the scene of AD research in the early and mid-1990s, when case-control trials reported that people who took these cholesterol-lowing drugs to prevent heart attacks and strokes appeared to have a lower risk of developing AD, too

As is often the case when small epidemiological studies generate an intriguing new hypothesis, cell and molecular biologists began investigating mechanisms by which these drugs might act in AD. In the case of cholesterol and statins, scientists indeed have established solid in-vitro as well as mouse and guinea pig data showing, for example, that cholesterol and its related forms regulate APP processing. This would suggest that statins might be able to prevent AD, but data on the ability of statins to affect Aß levels in humans are mixed.

Basic science also has described cholesterol- and APP-independent effects statins may exert on processes relevant to AD, such as antiinflammatory or neuroprotective actions that result from the ability of statins to inhibit isoprenylation of a variety of proteins.

The genetics front has done its small part by linking a half dozen genes related to cholesterol metabolism to AD, albeit in small studies that are not yet reproduced. Finally, hints of clinical success were indicated with small, published trials. In 2004

Edward Zamrini, Gerald McGwin, Jeffrey M. Roseman published a paper, "Association Between Statin and Alzheimer's Disease" in Neuroepidemiology 2004;23:94-98 and concluded "following adjustment for confounding factors, a statistically significant inverse association between statin use and AD was observed. The results lend support to looking at AD outcomes in trials of statins to further evaluate their possible beneficial effects."

However, more recent studies have brought doubt on this conclusion. Arvanitakis Z., Schneider JA., Wilson PS. et al in a study that appeared in the journal Neurology (Published online before print Jan. 16, 2008) found no relationship between the use of statins and Alzheimer's disease or neuropathologies associated with AD. They studied 929 Catholic clergy members who were enrolled in the Religious Order study. Participants (68.7% women, aged 74.9 at baseline) were free of dementia at baseline and were evaluated for up to twelve years. Brain autopsy data was available on 262 subjects. During the 12 year study, 191 subjects developed AD, of whom 16 (8.4%) were statin users at baseline. After adjusting for confounders, baseline statin use was not associated with risk of incident AD compared with non-use, nor was statin use at any time prior to death (17.9%) associated with global AD pathology. Persons taking statins were less likely to have amyloid but among those with myloid, no relation of statins to amyloid load was observed. Statin use also was not associated with tangles or infarction. The authors write: "Overall, these results do not support a relation between statins and AD or cognitive decline among older persons."

(2/14/08)- Baxter International Inc. has not announced the results of its double-blind placebo-controlled Phase II study of its Alzheimers' treatment drug Gammagard, but since the study involves only 24 people, there is much work that remains to be done with the drug. That study is headed by Norman Relkin who is associated with the Memory Disorders Program at New York-Presbyterian Hospital/Weil Cornell Medical Center in New York.

Gammagard is one of multiple intravenous immunoglobulin, or IVIG drugs that contain vast number of natural human antibodies. Those who feel that IVIG drugs may help in the battle against Alzheimers theorize that the drugs contain antibodies that can remove a brain-harming plaque associated with the disease.

(7/20/07)- A research study presented at the American Academy of Neurology's annual meeting in Boston by Victor W. Henderson, MD of Stanford University in California found that women who used estrogen hormone therapy before they were 65 years of age had about a 50% less chance of developing Alzheimer's disease or dementia than those who did not use estrogen replacement therapy (ERT) before age 65.

The study involved more than 7000 women aged 65 to 79 for an average of five years. Dr. Henderson is quoted as saying "It didn't matter how old the woman was when she started hormone therapy, how long or recently she took it, or what kind of prior therapy she had" as long as they started before age 65.

Obviously, this study does not apply to men, nor does it take into account potential adverse effects of ERT. This should not rule out a clinically relevant effect of ERT in certain women to reduce the chances of developing some form of dementia

(7/11/07)- The first transdermal patch to treat patients with mild-to-moderate Alzheimer disease has been approved by the FDA for usage in the U.S., the manufacturer has announced.

The Exelon (rivastigmine) patch is applied to the skin once daily. Its effect on memory and the ability to perform daily activities have been shown to be similar to those seen with the highest doses in the capsule form. The medication provides a regular and continuous dose throughout the day, according to its distributor Novartis Pharmaceuticals,

It is not a new medication, but a new way of delivering the medication that may make it easier to administer. Because the patch allows the drug to enter the bloodstream directly, it eliminate some of the gastrointestinal side effects associated with the drug when swallowed.

(6/26/07)- On May 15, 2007, this author attended the Psychiatry Grand Rounds given by Mount Sinai School of Medicine in NYC. The presenter was Guilio Maria Pasinetti, MD, Ph.D of the Mount Sinai staff. His topic was "Anti-hypertensive drugs as a beta-amyloid lowering treatment in Alzheimer's disease".

He described how memory deterioration is associated with the conversion of soluble monomeric amyloid protein into high weight soluble oligomeric amyloid beta which leads to memory deterioration. These soluble oligomeric amyloid beta peptides either lead directly to cognitive decline or lead to the development of amyloid plaques that result in cognitive decline.

He then went on to point out that there are now 56-57 antihypertensive drugs on the market that attempt to deal with hypertension. He divided them into seven different classes depending on their route of action.

While antihypertensive drugs have not proved effective as a class of drugs in dealing with cognitive impairments in meta studies, his study group tested each drug and has found that certain of these drugs do have a positive effect on memory in rats bred for Alzheimer's disease expression.

The next step would be to research in human trials the 6 drugs he found effective. These drugs included the K-sparing diurectic Amiloride, the calcium-channel receptor blocker Nicardepine, Propraolol HCL, Carvedilal, Valsartan, and Lorsartan with all others showing no statistically reliable memory enhancement qualities.

If this result holds up, we will have another series of medication to deal with the progressive deterioration of memory in Alzheimer's disease. Confirmation of this fact will take many years, with no guarantee that the same results will be shown in adults.

(6/22/07)- New results from a small 180 patient trial of Dimebon, a drug that was approved in Russia as an antihistamine continue to show good results from the six month extension of the original trial. All the patients in the study had mild to moderate cases of Alzheimer's disease.

Dr. Rachell S. Doody of the Baylor College of Medicine was the lead author of the study that was paid for by the drug's developer Medivation. The study was conducted in Russia.

Dimebon was approved as an antihistamine in Russia in 1983, but a scientist there found that it might work for AD. The new results are from a six-month extension of the original 6 month trial. The results show that the difference between the drug and the placebo at 12 months was either wider that at 6 months or the same, depending on the measure.

The patients on the drug were also better or the same at 12 months as at the start of the trial, suggesting that the drug improves functionality, not merely slowing its decline.

(9/24/06)- The following is the response from Harold Rubin to an emailed question to therubins concerning drugs that have been approved for usage in connection with the treatment of AD:

Dear Ms (---:)

(9/24/06)- We are not aware of the medication that you heard as a "cure" for Alzheimer's disease (AD). As far as we know, there is no cure for AD. The available medications deal with various symptoms of the disease, retarding the progress, but not reversing the disease process. The press has a habit of using hyperbole when describing a new medication or research study--part of the marketing of a new drug by the Pharmaceutical Companies.

We provide you the following information from the National Institute on Aging (NIA) on the state of the prescription medication for AD:

"Five prescription drugs currently are approved by the U.S. Food and Drug Administration to treat people who have been diagnosed with Alzheimer's disease (AD). Treating the symptoms of AD can provide patients with comfort, dignity, and independence for a longer period of time and can encourage and assist their caregivers as well. It is important to understand that none of these medications stops the disease itself.

"Four of these medications are called cholinesterase inhibitors. These drugs are prescribed for the treatment of mild to moderate AD. They may help delay or prevent symptoms from becoming worse for a limited time and may help control some behavioral symptoms. The medications are: Razadyne® (formerly known as Reminyl®) (galantamine), Exelon® (rivastigmine), Aricept® (donepezil), and Cognex® (tacrine). Scientists do not yet fully understand how cholinesterase inhibitors work to treat AD, but current research indicates that they prevent the breakdown of acetylcholine, a brain chemical believed to be important for memory and thinking. As AD progresses, the brain produces less and less acetylcholine; therefore, cholinesterase inhibitors may eventually lose their effect.

"The fifth approved medication, known as Namenda® (memantine), is an N-methyl D-aspartate (NMDA) antagonist.(This may be the medication you heard about). It is prescribed for the treatment of moderate to severe AD. Studies have shown that the main effect of Namenda® is to delay progression of some of the symptoms of moderate to severe AD. The medication may allow patients to maintain certain daily functions a little longer. For example, Namenda® may help a patient in the later stages of AD maintain his or her ability to go to the bathroom independently for several more months, a benefit for both patients and caregivers.

"Namenda® is believed to work by regulating glutamate, another important brain chemical that, when produced in excessive amounts, may lead to brain cell death. Because NMDA antagonists work very differently from cholinesterase inhibitors, the two types of drugs can be prescribed in combination."

The September 8, 2006 issue of the journal Cell, published by Cell Press has a study done at the UT Southwestern Medical Center at Dallas purporting to show that presenilin has a role in the process of familial AD, which accounts for about 5 percent of the AD cases. These presenilins form ion channels in mice.The effects of presenilin could account for about 80% of the calcium leaked from a membrane bound cellular compartment called the endoplasmic reticulum.Cells with the mutant presenilin become "overloaded" with calcium, which heightens the strength of the calcium signal. Moreover, the heightened calcium signal was reversed in mutant cells in which the scientists restored normal presenilin. They further showed presenilin's role in calcium signaling to be independent of its role in the production of amyloid ß.

The findings of this research suggests that drugs that restore normal calcium levels might be useful for treating Alzheimer's disease. The drug called memantine, which is already in use against Alzheimer's, acts on receptors that are a component of the calcium pathway. We thus think this was the drug you are referring to in your email.

This research is still in its early stages and needs to be evaluated in humans. However, from our read of the research studies, there is no indication that you cannot give an anticholinergic drug plus a NMDA antagonist in moderate to severe cases of AD. We strongly caution you that this must be discussed with the treating physician. The work on presenilin is preliminary and will take many years of research before it is approved by the FDA.

We can give you the following information to find out more about drug trials: The NIA maintains the AD Clinical Trials Database, which lists AD clinical trials sponsored by the Federal government and private companies. To find out more about these studies, contact the NIA’s ADEAR Center at 1-800-438-4380 or visit the ADEAR Center website at https://www.nia.nih.gov/health/about-adear-center . You also can sign up for e-mail alerts on new clinical trials as they are added to the database. Additional clinical trials information is available at www.clinicaltrials.gov .

We thank you for taking the time to read our web site and urge you to tell your friends about it. Do not hesitate to contact us again if you have any questions.

Harold Rubin, co-editor

(8/3/06)The World Health Organization (WHO) puts out a journal entitled "WHO Drug Information" that extracts reports from all over the world on drugs. Volume 20, #1, 2006 had an extract from the Australian Adverse Drug Reactions Bulletin, Volume 25, #1, Feb. 2005 that reported on adverse reactions to galantamine (Reminyl) in two placebo controlled trials. There was a higher mortality rate with galantamine than placebo and galantamine was not effective for mild cognitive impairment. This report also states "[T]he deaths were due to various causes which could be expected in an elderly population". It does suggest a yellow cautionary flag in using this drug.

Galantamine is one of four drugs approved for treatment of mild to moderate Alzheimer disease. The WHO publication indicates: "It is recommended that galantamine should only be used for approved indications of mild to moderately severe Alzheimer dementia. The safety and efficacy in other indications have not been established and the risks may outweigh the benefits."

"Caution should be used in patients with cardiovascular and pulmonary conditions, particularly after myocardial infarction and with new onset atrial fibrillation, second or third degree heart block, unstable angina and pneumonia."

(7/20/06)- Researchers of a study on the drug Aricept at the Mayo Clinic in Rochesterhave concluded that the drug appears to slow the shrinkage of the brain in people with the apolipoprotein E4 (APOE 4) gene. This gene has been determined to put people who have it at greater risk of getting Alzheimer's.

Dr. Clifford Jack of the Mayo Clinic was the lead researcher for the study. MRI images of the brains of 131 patients with mild cognitive impairment showed less shrinkage of the hippocampus, a key structure to memory function, in patients who got the drug, compared to those who received the placebo.

(12/14/05)-A progress update symposium held to provide information on translational medicinal science in CNS neurodegenerative diseases reported on the clinical status of Alzhemed. It is starting two phase III trials. So far, it has shown its biggest effect in mild Alzheimer's disease cases, lowering Cerebro Spinal Fluid amyloid beta 42/40 ratio, and in cognitive stabilization. Francine Gervis of Neurochem located in Montreal Canada gave this report. Alzhemed is an oral small organic molecule that has been designed to interfere with the association between glycosaminoglycans (GAGs) and Ab amyloid protein. It is thus thought to prevent GAGs from promoting b-sheet and amyloid formation, which lead to tangles and plaques considered as identifying markers for Alzheimer's disease.

(4/5/05)-Johnson & Johnson has sent out warning letters to doctors advising them about the deaths of 13 people who were taking its Alzheimer's drug Reminyl. The deaths occurred during clinical trials to test the drug's effectiveness in treating mild cognitive impairment. The drug has been used since 2001. J&J has also amended its packaging insert ot disclose the deaths. During the two-year studies, 13 participants taking Reminyl died while one patient who received a placebo died. The clinical trials involved about 2,000 people in 16 countries.

(9/12/04)-The preliminary results for Forest Laboratories Inc's. next generation drug to its recently launched drug Namenda were not encouraging. The drug neramexane did not improve patient's symptoms beyond existing therapies. The company had hoped that by combining neramexane to any of the three existing standard Alsheimer's therapies it would help maintain cognition and functionality better than using the drugs by themselves. Patients involved in this study had moderate-to-severe cases of the disease. Neramexane is designed to selectively block the effects associated with abnormal transmission of glutamate.

An experimental vaccine for Alzheimer's that was discredited as the result of some serious negative side effects is now being re-tested with the hope that the problem has been eliminated. The vaccine known as AN-1792 was co-developed by Wyeth Inc. of Madison, N.J. and Elan Corp of Dublin seeks ot halt or reverse Alzheimer's by stimulating antibodies that attack protein clumps known as amyloid plaques that have been found in the brain of people with AD.

The earlier clinical trial was cut short when the vaccine caused some patients' immune systems to attack health brain tissue as well., causing life threatening side effects. Researchers believe they have addressed the issue in a new version that they plan to begin testing soon. In reality the new treatment is not a vaccine, but rather it is designed to mobilize the body's own antibodies to fight off the existing disease.

The second-generation vaccine is called ACC-001, and it uses a small piece of the Alzheimer's amyloid protein to trigger the immune system. Again we would like to point out that this new "vaccine" is just at the earliest of testing stages that a drug must go through before it will gain approval from the FDA.

There are five drugs that have been approved by the FDA to treat mild to moderate Alzheimer's. None of the five is a cure for the disease. At best, all they do is hold back, for a short period of time, the ravages of the disease. Four of the drugs-Aricept (Pfizer Inc.and Eisai Co. of Japan), Exelon (Novartis AG), Reminyl (J&J and Shire Pharmaceutical) and Tacrine raise the levels of acetylcholine, a chemical that transmits nerve signals to the brain. The fifth drug, which is Namenda (Mematine) works on a different neurotransmitter.

A new drug is undergoing clinical study that has shown some degree of improvement in the battle against Alzheimer's disease. Neurochem Inc. announced that it is recruiting patients for an efficacy trial of its drug Alzhemed. To find out more about the study please go to the company's Web site at www.neurochem.com The study hopes to enroll950 patients over 18 months at 70 sites in the U.S. and Canada..

Alzhemed is at the leading edge of a wave of drugs that target the underlying illness rather than just treating the symptoms. Alzhemed helps prevent the formation of the plaques, which are made up of the protein beta-amyloid that build up on the brain that many scientists believe is the culprit behind Alzheimer's disease. Eli Lilly & Co. is also at a very preliminary stage in testing its drug that inhibits the enzyme involved in plaque formation.

Alzehemed works by preventing strings of beta-amyloid from clumping together, an activity that has to happen to form the dangerous plaques. Wyeth and Elan have halted tests on an earlier vaccine to prevent the build-up of plaque because more than a dozen people developed a dangerous inflammation of the brain. Earlier results for Alzehemed were promising but there were only 18 people used in that study.

The Chinese herb huperazine has been found to have many of the same properties as certain Alzheimer's drugs and is considered an interesting possibility in the battle against Alzheimer's. The herb boosts levels of acetylcholine, a neurotransmitter important in learning and memory.

Researchers from the University of Birmingham, in England, studied nearly 600 patients with mild to moderate Alzheimer's who received long-term treatment with Aricept or a placebo. The researchers concluded that Aricept did not effect the likelihood of the patients' being institutionalized or disabled after three years. The British government funded the study. The researchers concluded that there was "an absence of any significant delay" in disability and a "lack of any cost savings" for the health system.

A small study involving 404 patients at 37 different sites showed that two drugs that have been used in the battle to slow down the debilitating effects of Alzheimer's disease work even more effectively when they are used in tandem. The two drugs involved in the study are donepezil, which is sold under the brand name of Aricept (Eisai Inc. and Pfizer Inc. co-market the drug) and Memantine, which is sold under the brand name of Namenda (which is marketed by Forest Labs). The researchers, who published their work in The Journal of the American Medical Association, received grants and honorariums from the pharmaceutical companies that produce the drug.

The patients in the yearlong study were afflicted with moderate-to-severe Alzheimer's and had been taking the drug donezepezil (Aricept). The patients who also took the drug memantine scored better on tests for cognition and some quality-of-life measures than patients given a placebo along with the donezepil. The interaction between the two drugs was not clear. Mematine is a drug that counteracts the overproduction of the brain cell-killing chemical glutamate. Donezepezil prevents the breakdown of an important chemical messenger in the brain, acetylcholine, which commonly occurs with Alzheimer's.

A study by Merck & Co. showed that its rheumatoid arthritis drug Vioxx did not help in the prevention of Alzheimer's disease. An earlier study showed that both Vioxx and Aleve did not help in the treatment of people who already have the disease. Thus a deadly blow has been unleashed on those who thought that anti-inflammatory drugs could help in the battle against Alzheimer's disease.

The study had enrolled 1,457 elderly patients with mild cognitive impairment, and was at risk for developing AD. Half of the group received Vioxx and the other half received a placebo. The results showed 6.4% of the patients receiving the Vioxx developed Alzheimer's' compared to 4.5% in the placebo group. The study was halted after 189 cases developed Alzheimer's. Further analysis showed that the both groups had about the same chance of developing Alzheimer's disease.

On September 24, 2003 a Food and Drug Administration advisory panel recommended approval of memantine as a drug treatment for Alzheimer's disease patients, especially those in the late stages of the disease. This would be the first drug approved for treatment in connection with moderate to advanced Alzheimer's disease. The FDA usually approves the recommendations from its advisory panels.

Forest Laboratories, based in New York manufactures the drug. It will be sold under the brand name Namenda. The drug has been sold in Germany since 1980 and had been approved by the European Union in 2002. In clinical research studies, Namenda has been compared to a placebo. It has been shown that when Alzheimer's disease patients, use the drug, the cognitive decline was slightly slower than those using a placebo.

The drug blocks glutamate, a brain messenger chemical thought to damage or destroy nerve cells. Glutamate is an excitatory amino acid (EAA) neurotransmitter (release of glutamate by one neuron stimulates activity in its neighbors) involved in the neurotoxic events leading to cell death after CNS trauma and ischemia and in some neurodegenerative disorders. Too much glutamate is extremely toxic.

It is thought that much of the brain damage that occurs following stroke or in dementing illnesses, like Huntington's disease, is the result of excessive glutamate activity in the brain. But glutamate is also critical for many normal brain functions, including memory and learning. The four other drugs on the market stimulate acetylcholine levels in the brain.

While the advisory committee voted unanimously in favor of approval, it also noted possible adverse effects from the results of animal efficacy and safety studies. As cited above, the committee suggested that the drug itself may also destroy nerve cells. More importantly, they noted that the drug effects were minimal. This drug is not a cure for Alzheimer's disease, nor does it prevent progression of the disease. In the appropriate dosage, it could slow the progress of the disease. Forest Labs hopes to have the drug on the shelves sometime in the beginning of next year.

In a 6-month study involving 402 patients with moderate to severe Alzheimer's disease at 37 sites in the U.S. memantine was combined with aricept. Aricept is the most commonly prescribed Alzheimer drug in the U.S. Patients who took the combination saw a sustained improvement in cognitive and daily-living skills. Doctors have stressed that memantine isn't a cure and hasn't been shown to halt or reverse the processes of cell damage that causes Alzheimer's disease.

Results however from another clinical trial showed that memantine did not significantly improve awareness and reasoning in patients with mild to moderate Alzheimer's disease. The trial compared memantine plus a standard therapy with the standard therapy alone. There continues to be a great deal of hope among those using the drug, which also goes under the name of Axura from Germany, since it at least does show some improvement in daily-living skills.

The results from a study sponsored by the U.S. government's National Institute on Aging (NIA), of the anti-inflammatory drugs failed to show that they slowed the progression of Alzheimer's disease. This does not affect the seven-year study financed by the National Institute of Health to see if the drugs can help prevent Alzheimer's disease. The NIA is continuing its study as to whether or not the anti-cholesterol drugs known as statins can delay the symptoms of Alzheimer's disease.

Dr. Paul S. Aisen of the Georgetown University Medical Center in Washington was the leader of the study. Dr. Aisen said that he was disappointed with the results of the study. He went on to say: "We saw no evidence of benefit." The study compared three treatments: Vioxx, the antiinflammatory drug made by Merck & Co.; naproxen, an over-the-counter medication sold under several brand names including Aleve; and a placebo, or sugar pill. The two drugs showed no better results for the patients taking them then it did for the patients taking the placebo.

The Danish pharmaceutical company Lundbeck LUN.CP and the German company Merz Pharmaceutical said that clinical studies of their drug Memantine for treatment of advanced Alzheimer's disease has shown that the drug does slow down the progression of the disease. The drug has been approved for use in Europe and is under review by the U.S. FDA. Forest Labs has the marketing rights in the U.S. for Memantine. The drug is not expected to be on the U.S. market for approximately two years. Forest Labs had previously announced the withdrawal of its New Drug Application for the drug, and added that it would hopefully be able to refile the application by year's end with an amended application that would include new study data.

It is estimated that about 15 million people suffer from Alzheimer's worldwide and about 4 million suffer from the disease in the U.S. In the Memantine study researchers compared patients taking the drug with those taking a placebo during a 28-week trial period. The study found that the patients taking Memantine required less assistance from caregivers than those in the placebo group. The study was a small one since there were only 181 patients involved in it. The Memantine patients also scored better on a test assessing memory, language and social interaction.

Public Citizen's Health Research Group (a consumer advocacy group) sent a letter to Health and Human Services Secretary Tommy Thompson requesting that the government put an end a study as to whether or not two pain relievers prevent Alzheimer's disease. The drugs in question are Bayer AG's Aleve and Pfizer's Celebrex.

The letter charges that the patients participating in the study were not adequately informed about the possible risks of the drugs. The letter also alleges that the drugs likely won't work and that they put the health of hundreds of patients at risk. So far, about 1,000 patients are enrolled in the seven-year study, which is sponsored by the National Institute of Aging. The study hopes to enroll over 2,600 patients.

Researchers have reported that people taking nonsteroidal anti-inflammatory drugs (NSAIDs) have a lower risk of developing Alzheimer's disease. Different NSAIDs work differently than some other NSAIDs so much research work remains to be done in this area.

According to Sidney Wolfe, director of Public Citizen's Health Research Group " To essentially risk worsening their health with no probability of any benefit is just unethical and exploitative." According to John Breitner, the University of Washington researcher who heads the National Institute of Aging prevention study, his research indicates that Aleve protects against Alzheimer's while Celebrex is worth studying because the enzyme it targets I overactive in the brains of Alzheimer patients.

The following is a list of drugs that this site has compiled that are no longer in development. This does not mean that research chemists are not tinkering with its components to come up with an altered chemical version that may eliminate the side effects or be used in some other disease. (Witness the drug thalidomide.) 

ABT-418, AF-102B, Besipirdine, Idebenone, Linopirdine, LU 25-109, Metrifonate, Milameline, Oxiracetam, Physostigmine, Propentofylline, Sabeluzole (formerly Reminyl), Suritozole, SB 202026 (Memric), Velnacrine, Xanomeline Oral Formula

Drugs Presently in Clinical Trial

ALCAR (acetyl-l-carnitine HCL) in phase III clinical trails, manufactured by Sigma-Tau Pharmaceuticals, attempts to provide a possible protective effect against neuritic tangles. Tangles, which are cytoskeletal components that affect the way the neuron functions, are found inside the neuron, while plaques are found outside the neuron. Breakdown of neurons result in loss of synapses, the unit of communication between cells.

AN-1792, manufactured by Elan Corporation is the "vaccine" described above. It is a synthetic form of the 42 amino acid beta amyloid peptide. See the articles in our Alzheimer’s disease folder for role of beta amyloid peptide in AD. Recently Elan announced the suspension of patient dosing in it Phase 2A study of AN-1792 and the suspension of clinical trials with this drug.

Beta and Gamma Secretase Inhibitors are proteases that help produce amyloid beta peptide involved in plaque formation. The enzyme Secretase breaks down the amyloid precursor protein into the amyloid beta peptide. However, there is more than one type of Secretase. The feeling is that the beta and gamma forms of Secretase are of primary importance in the process and that the inhibitor will diminish amyloid production in the individual with Alzheimer’s disease without diminishing the effects of other forms of Secretase.

Cerebrolysin, manufactured by Ebewe Pharmaceutical, is in clinical phase II/III development. It is made from brain proteins and it has the potential to exert nerve growth factor-like activity that could improve memory.

CX-516 (Ampalex), manufactured by Cortex Pharmaceuticals, is in phase II of development. Involved with process that increases the flow of current that takes place when glutamate binds to receptors. Glutamate has a role in memory. Also looking at this drug for treatment of schizophrenia, where one of the symptoms is cognitive impairment.

Dapsone (Avlosulfon), manufactured by Immune Network, Inc, is in phase II of development. This is an anti-inflammatory medication that may slow the progression of Alzheimer’s disease. It is used to treat leprosy. Studies indicate a low incidence of Alzheimer’s disease in aged leprosy patients.

Eptastigmine MF-201, manufactured by Mediolanum Pharmaceuticals, is in phase III of development. It is a long-acting cholinesterase inhibitor.

Galanthamine, manufactured by Hoechst Marion Roussel Inc, Shire Pharmaceuticals Group and Janssen Pharmaceutica, is in phase III of clinical trials. It has been approved in Austria and has been marketed for other uses in Eastern Europe for many years. It is a reversible cholinesterase inhibitor and an allosteric nicotinic agonist, thus giving it more cholinergic activity and other neurochemical and behavioral consequences that other drugs may not share.

Huperzine A is an alkaloid derived from a traditional Chinese herbal remedy for fever. Clinical trials are being planned to see if it may prove helpful in memory enhancement. It is in current use in China. (One of the editors of this site is arranging a trip to China to gather more information on this herb.)

Ibuprofen, manufactured by American Home Products, Upjohn, Bristol Myers Squibb, is in phase III of development for use in AD. This is another drug that may reduce inflammation in the brain thus delaying the onset of Alzheimer’s disease.

Melatonin appears to be involved in regulation of sleep. Sleep problems are not uncommon in AD individuals. The Alzheimer’s Disease Cooperative Study is seeking participants in a clinical trial studying the efficacy of melatonin as a treatment for sleep disturbances in AD.

Memantine The Danish pharmaceutical company Lundbeck LUN.CP and the German company Merz Pharmaceutical said that clinical studies of their drug Memantine for treatment of advanced Alzheimer's disease has shown that the drug does slow down the progression of the disease. The drug has been approved for use in Europe and the U.S. Forest Labs has the marketing rights in the U.S. for Memantine, which it is marketing under the name Namenda.

Naproxen, Aleve, Anaprox, Naprosyn, manufactured by Syntex and Proctor & gamble, Roche Pharmaceuticals, is in phase III of clinical development for use with individuals diagnosed with AD. These over the counter nonsteroidal antiinflammatory drugs (NSAIDs) reduce inflammation that may trigger the AD process.

NeoTrofin AIT-082, manufactured by Neo Therapeutics Inc., is in phase III of clinical research. Research literature indicates: "It acts at the site of heme oxygenase to generate carbon monoxide and by activation of guanylyl cyclase induces a cascade of biochemical reactions through the second messenger system leading to the production of mRNA for neurotrophins."

Nefiracetum is in phase II of clinical trails, acting on nicotinic acetylcholine receptors, accelerating acetylcholine turnover and release enhancing cellular communication via synapses.

Xanomeline Skin Patch, manufactured by Eli Lilly, is in phase II of clinical trails. As stated above, the oral form of this drug is no longer in development, but Eli Lilly still thinks this drug has a role to play in stopping cognitive decline because of its role as a selective M1 muscarinic receptor agonist. Delivery of medication via a skin patch increases the adherence to the prescribed drug regimen. May also help those AD patients who have trouble swallowing, when brain stem dysfunction is involved along with cortex cognitive dysfunction.

Research cognitive scientists are still pursuing the molecular process that goes on in the brain resulting in memory. Memory is a complex generic concept including verbal fluency memory, working memory, spatial memory, explicit memory etc. Clarification of the process of memory, along with the work being done on the human genome, may bring about the focused treatment of Alzheimer’s disease beyond possible slowing down of symptom progression.

Presently, the primary objective of treatment is to achieve some improvement in cognitive and behavioral symptoms. It might also prove helpful if individuals suffering from AD reduce or stop taking prescribed or over the counter drugs that may impair cognition. This could include alcohol, benzodiazepines and any other drug that has anticholinergic effects.

For the elderly, the past recedes, moving further and further away. Richard Eder, a literary critic of the New York Times, describes memories as "Stretch[ing] back into mist". There is much to be done to enhance the quality of fading mortality. All of us have the possibility of gaining from these clinical trials. Time will tell.

In previous parts to this series of articles on Alzheimer's, we had mentioned that there are many drug therapies being considered by pharmaceutical companies as possible treatments for the disease. Many of these might never get to the market because of various reasons, but it may be worthwhile for our readers to know of these drugs, and, if they want further information on their status, they could contact the developer mentioned below.

Autopsies have shown that the brains of Alzheimer's sufferers have extensive clutters of amyloid plaques. Recently 3 drug companies have been attacking amyloid plaque growth in the hope that this can prevent Alzheimer's Disease. The 3 drug companies are Elan Corp.PLC, Bristol Myers Squibb Co., and Eli Lilly & Co. It has been demonstrated in test tubes that amyloid plaque can damage nerve cells. The work in this area is thought to have originated in a young start up company called Athena Neurosciences (now a subsidiary of Elan) Initially work in this area was hindered by the fact that there were no mice available with the gene that produced amyloid plaque.

It wasn't until 1994 that some mice were made available to the scientific community that had the gene. Extensive clutters of the plaque were found in autopsies performed on the brain of these mice. The thought then arose that it would be possible to inject fragments of the amyloid into the body that in turn would stimulate the production of antibodies to the amyloid. Mice do not develop Alzheimer's disease.

This would trigger an immune response that would kill the plaque. The Company reported in the Journal of Nature in 1997 that monthly shots given to young mice prevented the formation of the plaque altogether. When given to older mice it stopped the formation of additional plaque and even reduced somewhat the amount of plaque that already existed on the brain.

Bristol-Myers has collaborated with a biotech company called Sibia Neurosciences to try and prevent the growth of the amyloid plaque. The compound that they have perfected is expected to undergo clinical testing by the end of this year. The trials will involve several thousand subjects and last for 2 years. Lilly is also expected to begin testing of their compound to prevent amyloid plaque growth by the end of the year.

At latest count there are an estimated 4 million Alzheimer's sufferers in the United States today. For obvious reasons it is impossible to test the brains of these suffers while they are still alive. Therefore we do not know if the plaque is the cause of Alzheimer's or is the result of Alzheimer's. This is a promising avenue to proceed along but no one knows if it will be an answer.

The table will list the research name of the drug being tested for its effect on the process of the development of Alzheimer’s disease along with the name of the developing corporation as well as what the drug is intended to do. Those products that have an asterisk are being developed outside the United States..

Potential New Alzheimer Disease Drugs

Product	Developer	Status	Indication
AF-102B	Forest Laboratories Inc.	Phase II/III clinical trials	Alzheimer disease
AIT-082	Neotherapeutics Inc.	Phase I clinical trials	Memory impairments with Alzheimer’s disease
Alcar	Sigma-tau pharmaceuticals	Phase I clinical trials	Early onset Alzheimer’s disease
Alzene	Ivex Corp.	Phase II clinical trials	Alzheimer disease
Ampelex	Cortex Pharmaceuticals	Phase I/IIa clinical trials	Alzheimer disease
APP modulators	Sibia Neuroscience Inc.	Preclinical trial development	Alzheimer disease
Beta amyloid protease inhibitors	Scios Inc.	Preclinical trial development	Alzheimer disease
Celebra	G. D. Searle & Co.	Phase II clinical trials	Alzheimer disease
CEP-1347/KT7515	Cephalon Inc.	Preclinical trial development	Alzheimer disease
CHF 2060*	Chiesi Farmaceutici S.p.A.	Phase I clinical trials	Alzheimer disease
CHF2819*	Chiesi Farmaceutici S.p.A	Preclinical trial development	Alzheimer disease
Cognex CR	Parke-Davis Research	Phase III clinical Trials	Alzheimer disease
Corticotropin releasing factor	Neurocine Biosciences Inc.	Preclinical trial development	Alzheimer disease
CP-118,954	Pfizer Inc.	Phase II clinical trials	Alzheimer disease
DHEA	Neurocine Biosciences Inc.	Phase II clinical trials	Alzheimer disease
Eldepryl	Watson Pharmaceuticals	Phase III clinical Trials	Alzheimer disease
Eldepryl	Somerset Pharmaceuticals	Phase III clinical Trials	Alzheimer disease
Exelon	Norvartis Pharmaceuticals	Awaiting approval	Alzheimer disease
GR253035*	GlaxoWellcome Inc.	Phase I clinical trials	Alzheimer disease
HMR24	Hoechst Marion Roussel Inc.	Preclinical trial development	Alzheimer disease
Idebenone	Takeda Chemical Industries Inc.	Phase II clinical trials	Alzheimer disease
Marinol	Unimed Pharmaceuticals	Phase II clinical trials	Alzheimer disease
emric	SmithKline Beecham	Phase III clinical Trials	Alzheimer disease
Metrifonate	Bayer	Awaiting approval	Mild-to-moderate dementia of Alzheimer type
Milameline	Hoechst Marion Roussel Inc.	Phase III clinical trials	Alzheimer disease
NDD-094	Novartis Pharmaceutical	Phase I clinical trials	Alzheimer disease
Pakio	Hoffman La Roche	Phase III clinical trials	Alzheimer disease
Razadyne (formerly Reminyl)	Shire Pharmaceutical Group, and Johnson & Johnson	Approved by the FDA	Mild-to-moderate Alzheimer disease
Sermion	Pharmacia & Upjohn	Phase III clinical trials	Alzheimer disease
SIB-1553A	Sibia Neuroscience Inc.	Preclinical development	Alzheimer disease
SL 65.102	Synthelabo	Preclinical development	Alzheimer disease
SR 46559*	Sanofi S.A.	Phase II Clinical Trials	Alzheimer disease
SR 57446*	Sanofi S.A.	Phase IIb clinical trials	Alzheimer disease
Synapton	Forest Laboratories Inc.	Awaiting approval	Alzheimer disease
Viviq	Hoechst Marion Roussel Inc.	Phase III clinical trials	Alzheimer disease and vascular dementia
Xanomeline	Eli Lily And Co	Phase II Clinical Trials	Alzheimer disease
Zyprexia	Eli Lily And Co.	Phase II Clinical Trials	Psychosis related to Alzheimer’s disease

As the population ages, it has been predicted that more individuals will develop Alzheimer’s disease. Alzheimer's disease ranks as the eighth-leading cause of death in the U.S., and accounted for 44,507 deaths in 1999.

It is estimated that Alzheimer’s disease costs society about $33 billion annually, with average lifetime cost per individual at about $174,000. In 1999, the United States government will spend approximately $400 million for research, which works out to $1 for every $250 the disease now costs. This money mainly goes for clinical trials designed to find new and better medications to deal with the symptoms related to the disease, and hopefully to cure the disease.

There may be some readers of this article who know of individuals who would like to participate in this research with the knowledge that in a research project the investigators are looking at the product rather than the individual patient. These trials are funded by the National Institute of Health and are public information.

We will send a list of the study sites, with names of the Principle Investigators to those readers who request it in writing (Rehabilitation Strategies Unlimited, c/o Harold Rubin, 255 West 90^th Street, New York, NY,10024). Please include a self-addressed stamped envelope. We will also include names of pharmaceutical companies that sponsor indigent drug services for needy individuals who would otherwise be unable to afford such medication.

The following is a list of drugs that this site has compiled that are no longer in development. This does not mean that research chemists are not tinkering with its components to come up with an altered chemical version that may eliminate the side effects or be used in some other disease. (Witness the drug thalidomide.) 

ABT-418, AF-102B, Besipirdine, Idebenone, Linopirdine, LU 25-109, Metrifonate
Milameline, Oxiracetam, Physostigmine, Propentofylline, Sabeluzole (formerly Reminyl)
Suritozole, SB 202026 (Memric), Velnacrine, Xanomeline Oral Formula

The following is a list of Web sites that may help you gather more information about studies that are presently being conducted to further the research on Alzheimer's disease.

The ClinicalTrials.gov web site developed by National Institute of Health through its National Library of Medicine, contains about 5,000 clinical studies sponsored primarily by the National Institutes of Health.

The CenterWatch Clinical Trials Listing Service web site is less detailed, but includes trials not listed in the Alzheimer's Disease Clinical Trials Database.

The Alzheimer's Association can provide a list of study centers in your region. Send e-mail or phone 800-272-3900.

The Danish pharmaceutical company Lundbeck LUN.CP said its drug Memantine for treatment of Alzheimer's disease was recommended for approval by a European Union committee. Forest Labs has the marketing rights in the U.S. Memantine is the first drug to do clinical trials in patients with severe Alzheimer's although it is not likely to be more effective than the current Alzheimer drugs on the market. The drug is not expected to be on the U.S. market for approximately two years.

Elan and Wyeth-Ayerst Labs (a division of American Home Products) announced that it has suspended patient dosing in it Phase 2A study of AN-1792, which we discuss in Study Number 2 below. The study has been suspended and the drug will not be going forward in development because four patients were reported to have signs of inflammation of the Central Nervous System (CNS).

The December 21, 2001 issue of Nature indicated that researchers using a transgenic mouse model of Alzheimer's disease were able to demonstrate that accumulation of amyloid-beta protein deposits correlated with cognitive decline. They showed that a vaccine could reduce the amyloid-beta protein deposits and reduce impairments in learning and memory.

This sounds like good news, but for many in the scientific community, there still is a question of whether it is the amyloid-beta plaques that cause dementia. Some researchers are focusing in on two separate Alzheimer disease genes located on chromosome 10 that play a part in regulating amyloid-beta levels.

A number of our readers have asked us about volunteering for studies being done with possible new AD medications.

The FDA has granted approval to Johnson & Johnson for its drug Reminyl to treat mild-to-moderate cases of Alzheimer's disease. According to a company spokesman the drug will be available to the public starting in May 2001. Its price will be about the same as 2 other medications now being used to treat Alzheimer's disease. The other 2 drugs are Aricept, sold by Pfizer, Inc., and Exelon sold by Novartis AG of Switzerland. Reminyl was shown to be effective in improving or helping to stabilize patients' ability to think and perform daily tasks of living. The test group used to evaluate the drug consisted of 2,650 subjects. Side effects reported in connection with taking the drug included nausea, vomiting, anorexia, diarrhea and weight loss. The Janssen Research Foundation, a subsidiary of Johnson & Johnson developed the drug, under a co-development and licensing agreement with Shire Pharmaceuticals Group PLC.

The May 10, 2000 issue of JAMA (an American Medical Association publication) column titled "The World in Medicine" discussed a "promising" new drug for Alzheimer’s disease treatment. The drug, Galantamine Hydrobromide, marketed as Reminyl, is for treatment of mild to moderate cases of Alzheimer’s disease. The European studies indicated that 24 mg/d is the dosage that is most effective, improving scores on the Alzheimer’s Disease Assessment Scale in memory, language, orientation and other aspects of cognition over a one year period.

Galantamine is classified as Acetylcholinesterase inhibitors. It also appears to act on nicotine receptors in the brain. Both the acetylcholine and nicotine receptors have been suggested as areas related to cognitive impairment.

It remains to be seen whether this drug is any better than those already on the market in the USA. It does not pretend to be a cure for Alzheimer’s disease, but may retard the cognitive decline.

Researchers are still trying to pin down the process of memory impairment in the brain. Neurotransmission in the brain is a complex phenomenon, involving different receptor sites. Different mechanisms of action may precipitate different profiles of AD and call for different forms of treatment. The hallmarks of Alzheimer’s disease involve extensive amyloid plaque formation, neuritic dystrophy, synaptic loss and gliosis. These pathological and biochemical changes are the target of drug treatment. It is not yet known what causes these pathologic changes, although genetics and age are risk factors and theories abound.

Media reports have been suggesting that a "vaccine" is on the way which is being developed by Elan Corporation. Please note that research is only in the first clinical trial phase of development to make people immune to beta-amyloid plaque formation. This month's issue of the journal Nature reports on a study performed by scientists at Massachusetts General Hospital in Boston and Elan Corp of Dublin The brains of mice with genetically induced Alzheimer's disease were injected with an antibody known to attack beta-amyloid, a plaque that normally builds up and clogs the brains of people with Alzheimer's disease.

A protein injection melted away the brain-clogging beta-amyloid plaque. The literature indicates that you can have beta-amyloid plaque formation and not have symptoms of AD and that plaque formation is a ubiquitous phenomenon in human beings. It will be many years before this vaccine becomes available to the public and then, only if it passes all phases of drug development and long-term clinical use. Some scientists believe that the beta-amyloid buildup is merely a symptom of Alzheimer's disease and that therapies aimed at clearing them up will not cure the underlying disease.

To keep our readers informed, we present a further list of drugs in clinical trails. These drugs are based on the theory that stimulating the cholinergic, muscurinic or nicotinic synapses could alter the progression of the disease. Most are aimed at palliative treatment. Presently, cholinesterase inhibitors are the only approved pharmaceutical treatment of AD. Cholinesterase inhibitors block acetylcholinesterase, preserving acetylcholine for a longer period of time, thus preserving brain cell communication. The most common adverse events of this class of drugs involve the gastrointestinal tract: nausea, vomiting and diarrhea. Physicians will lower the dose when these affects show up, until the individual becomes tolerant and then building the dose up again. The drugs listed below may have a wider range of adverse effects and are not available for treatment of AD in the USA.

Please see the other articles in the series on Alzheimer ’s disease:

See: Alzheimer's Disease Part I-Medications for Alzheimer's.
See: Alzheimer’s Disease Part II- Selegiline and AD.
See: Alzheimer's Disease Part III- Use of Gingko Biloba in memory problems of Alzheimer patients.
See: Alzheimer's Disease PartIV-Alternative Treatment.
See: Alzheimer's Disease Part V-Possible New Drugs for Alzheimer's Disease Treatment.
See: Alzheimer's Part VI -Early Diagnosis.
See: Alzheimer's Part VII -New Medication-Metrifonate
See: Alzheimer’s Disease Part VIII - Implications of Longer Life Expectancies
See: Alzheimer’s Disease Part IX- -Estrogen and Alzheimer’s Disease
See: Alzheimer’s Disease Part X-- -Pocket Smell Test
See: Alzheimer’s Disease Part XI - Ethical Care
See: Alzheimer's Disease Part XII- MAO
See: Alzheimer's Disease Part XIII-Possible Screening for ADt
See: Alzheimer's Disease Part XIV-Donepezil
See" Alzheimer's Disease Part XV-Cerebroylsin
See: Alzheimer's Disease Part XVI-MCI
See: Alzheimer's Disease Part XVII-Research Summary
See: Alzheimer's Disease Part XVIII- NSAIDs
See: Alzheimer’s Disease-Part XIX- Vitamin E
See: Alzheimer's Disease-Part XX-Clinical Trials
See: Alzheimer's Disease Part XXI-The Brain
See Dementia with Lewy Bodies- Part XXII-by Gourete Broderick
See: Alzheimer's Disease-Part XXIII-HMG
See: Alzheimer's Disease-Part XXIV-Psychosisl
See: Alzheimer's Disease-Part XXV-A PrequelSee:
See: Alzheimer's Disease-Part XXVI-Amyloid-beta Hypothesis Controversy
See: Alzheimer's Disease-Part XXVII- AD and Diabetes
See: Alzheimer's Disease-Part XXVIII - Insulin and AD

FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "HOW TO SELECT A NURSING HOME".

by Allan Rubin and Harold Rubin
updated July 8, 2024

http://www.therubins.com

To email: harold.rubin255@gmail.com or allanrubin4@gmail.com

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