Pfizer recently announced that two of the three ongoing Phase III clinical trials (the CONSTELLATION and the CONTACT studies on moderate- to severe-AD) are being canceled. The third (CONCERT, on mild- to moderate-AD) will continue recruiting.
Those of us in the open-label extension of the completed (and very successful) dimebon safety trial are being notified Pfizer intends to cancel the extension, and stop providing us with the drug. This, despite the fact that our agreement with Pfizer very specifically says that they will continue to give us the drug, for free, until they either halt all commercialization efforts or bring the drug to market. It is unclear whether patients in the open-label extension of the completed CONNECTION trial (the one which failed to show efficacy) will continue to receive the drug.
Many people feel that our loved ones have improved on dimebon. The Alzheimer's Reading Room is trying to pull together enough information from us to publish an article, and see if we can't get Pfizer's decisions reversed.
Please send an email containing specifics about your dimebon experience. From Bob DeMarco:
Which Dimebon trial were you enrolled in?
Can you give me 2 or 3 examples of "what doing better means to you"?
Did you reach the open label extension phase?
If I can get more feedback from others that were in the trial, I'll publish an open letter to David Hung on the website and then we can see if we can get the broader media to pick up on it.
Tell me if you would like to use your name or publish anonymously. Real name usually carries more weight.
If you can help me find others to write up their feelings that would be helpful. Privacy is an issue.
What this really means, who knows ... BUT, my wife is in her 5th month of the CONCERT trial and maybe, just maybe, there are some limited positive effects. She is also enrolled in a longitudinal study and it was time for her annual eval for that study ... which is totally unrelated to the clinical trial. Well, despite severe declines in short term memory and other areas this past year, her 'mini mental' exam score was actually a few points higher on Monday than it was a year ago! We all know that the mini mental often has no relationship to what we observe in actual daily functioning in the real world ... many of us have seen how these scores simply do not correlate well with the 24/7 real world we and our spouses live in. However, despite bombing on the short term memory portions of the test, her overall score did go up after a year, something we did not expect to happen. So who knows ... maybe after being in the Concert clinical trial for a year (her trial ends in Janurary) either dimebon + aricept ... or the placebo effect ... will result in a slowing of delcine in some language areas!
Friday, June 11, 2010 Will the New Database of Alzheimer's Patients Help Drugs Like Dimebon Reach Alzheimer's Patients
ShareThis By Bob DeMarco Alzheimer's Reading Room
A group of major pharmaceutical companies have agreed to contribute data from failed Alzheimer's disease clinical trials that included more than 4,000 patients to a new database. The purpose of the new database is to share information with the goal of trying to gain a better understanding of what is going wrong in the trials, and to help discover new and better ways to develop drugs for the treatment of Alzheimer's disease.
"Companies said they're running into a stone wall with Alzheimer's and Parkinson's," said Ray Woosley, chief executive of the Critical Path Institute, which oversees the coalition. "We really believe drugs are failing because we honestly don't understand the disease."
From my view, this is an excellent step forward. This should allow for collaboration across labs and the sharing of intellectual capital. At least I hope that happens.
It is my belief that the recent failure of the Pfizer (PFE) Medivation (MDVN) Dimebon clinical trial shows a major flaw and weakness in the current clinical trial process.
We know from the experience of my mother and the many readers that have contributed their Dimebon clinical trial experiences on this website that Dimebon can/does work in some Alzheimer's patients.
Nevertheless, the Medivation Dimebon Connection Study failed miserably. Based on those results Medivation canceled the clinical trials for patients in the moderate to severe stage of Alzheimer's.
Why? The Connection study was conducted on patients with mild to moderate Alzheimer's disease.
Is is possible that by sharing data and by allowing for broader collaboration that an alternative method of conducting a clinical trial could be discovered?
Is is possible that if the Dimebon clinical trial were rerun on the specific subset of patients that showed memory and behavior improvement that the drug would pass the safety and efficacy tests necessary for FDA approval?
Would a clinical trial of this type help Pfizer Medivation discover whether or not Diembon does in fact have "efficacy". Will the FDA get out of the way and allow for this new kind of clinical trial?
Is is necessary to demand an "all or none" policy when it comes to a clinical trial? Is the current threshold of statistical significance two high when it comes to Alzheimer's or similar diseases that have no known cure or long term treatment?
In the case of Dimebon, would it be possible to identify specific patient characteristics if only those patients that showed a positive outcome were studied in a next round clinical trial? Are their a subset of patients that were in the trial that did, would, and can benefit from Dimebon?
My point. My mother was enrolled in a Dimebon clinical trial that was cancelled. During the weeks 4 through 18 my mother showed clear memory and behavior improvement. It was like she went into a time machine and went back 4 years or more.
Why shouldn't my mother be able to purchase the drug? Does a drug have to work for every person suffering from Alzheimer's to be approved? Lets face it, we already know the existing drugs don't work for everyone.
Is it really about money (profit), or is it also about flaws in the current clinical trial process and the way they are conducted? Most likely, both.
Do we need new rules to allow for the approval of new medications? Does a drug need to yield billions in sales in order to be commercialized? Or are half billions enough?
Should consumers be allowed to decide what they want to put in their mouths? In the case of Dimebon there were no significant safety issues discovered in the thousands of patients that participated in the clinical trials.
Since there were no safety issues, should we be allowed to purchase the drug after signing a binding legal document that holds both Pfizer and Medivaton harmless across any and all eventualities?
Public Release of Alzheimer's Clinical Trial Data By Pharmaceutical Researchers
First Combined Pharmaceutical Trial Data on Neuro-degenerative Diseases; Shared Resource from Unique Public-Private Partnership Will Help Accelerate Alzheimer's, Parkinson's, and Other Brain Disease Research
A new database of more than 4,000 Alzheimer's disease patients who have participated in 11 industry-sponsored clinical trials will be released today by the Coalition Against Major Diseases (CAMD). This is the first database of combined clinical trials to be openly shared by pharmaceutical companies and made available to qualified researchers around the world.
It is also the first effort of its kind to create a voluntary industry data standard that will help accelerate new treatment research on brain disease, as patients with other related brain diseases are expected to be added. The level of detail and scope of this database will enable researchers to more accurately predict the true course of Alzheimer's, Parkinson's, Huntington's, and other neuro-degenerative diseases, thereby enabling the design of more efficient clinical trials. Patient identifiers will not be included in the database, thereby ensuring patient privacy.
CAMD is a formal consortium of pharmaceutical companies, research foundations and patient advocacy/voluntary health associations, with advisors from government research and regulatory agencies including the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute on Aging (NIA). CAMD is led and managed by the non-profit Critical Path Institute (C-Path), which is funded by a cooperative agreement with the FDA and a matching grant from Science Foundation Arizona.
"The U.S. Food and Drug Administration has supported and actively participated in this innovative and unprecedented public-private partnership from its inception," said Joshua Sharfstein, MD, Principal Deputy Commissioner, FDA. "The agency is strongly committed to CAMD and other regulatory science collaborations that can speed safe and effective treatments to the public."
In addition to sharing data, the pharmaceutical members of CAMD have agreed to use the new common data standard established for Alzheimer's disease by the standard-setting organization, CDISC, in their future submissions for drug approvals.
The Clinical Data Interchange Standards Consortium (CDISC) is a global, multidisciplinary, non-profit organization that has established standards to support the acquisition, exchange, submission, and archive of clinical research data and metadata. CDISC standards are vendor-neutral, platform-independent, and freely available via the CDISC website. This will add greater efficiencies to the FDA's review process and make it possible for new products to reach the market more quickly and with greater assurances of safety and effectiveness.
This unprecedented data sharing is game-changing for companies that are developing new therapies for neuro-degenerative diseases," said Raymond Woosley, MD, PhD, President and CEO of Critical Path Institute (C-Path). "Scientists around the world will be able to analyze this new combined data from pharmaceutical companies, add their own data, and consequently better understand the course of these diseases."
Mark McClellan, MD, PhD, who launched FDA's Critical Path Initiative during his tenure as FDA Commissioner, also noted the need for better evidence.
"Too many treatments fail in the last stages of research, wasting millions of dollars and years of research time. To get to faster, more efficient development of safe and effective treatments, we must have a better understanding of diseases at the molecular level. The CAMD database is a promising step in this process for neurodegenerative diseases," said Dr. McClellan, who is now the director of the Engelberg Center for Health Care Reform and Leonard D. Schaeffer Chair in Health Policy Studies at the Brookings Institution.
Roughly 6.5 million people in the U.S. are afflicted with Alzheimer's and Parkinson's diseases, with costs reaching as much as $175 billion annually. Worldwide there are already an estimated 30 million people with dementia alone. By 2050, the number will rise to over 100 million. Halting or slowing the progression of these diseases will prevent untold suffering and save tens of billions of dollars every year.
"Data sharing is the backbone of several CAMD projects designed to identify patients who might develop brain diseases, i.e., before symptoms are apparent," said Marc Cantillon, MD, Director of C-Path's Coalition Against Major Diseases. "Our goal is to develop tools to prevent or slow these diseases so patients can maintain independence and quality of life."
The CAMD database will allow researchers to design more efficient clinical trials that have the maximum chance of demonstrating if a new treatment is truly safe and effective. In addition, the coalition is identifying biomarkers that identify patients in the very early stages of Alzheimer's disease and Parkinson's disease.
According to Maria Isaac, MASc, MD, PhD, Scientific Administrator, Scientific Advice, Human Medicines Special Areas Sector of the European Medicines Agency (EMA), "Within the context of the Innovative Medicines Initiative (IMI) in Europe, the EMA is committed to similar goals as C-Path's consortia, i.e., to help biopharmaceutical drug development, for the benefits of patients. The Agency is especially interested in reviewing CAMD's Alzheimer's biomarkers and disease progression models."
This is certainly a step in the right direction. My wife is approaching the halfway point in her participation in the year-long Phase III CONCERT clinical trial with Dimebon and Aricept and I have been assured by the principal researcher at the ADRC that the plug will not be pulled until after the entire year runs its course. In fact, I was told that they are still continuing to recruit new patients for this study because Medivation/Pfizer remain optimistic that after a year there will be positive results to share. All I can say is ... I hope so!
Sunshyne, could you email what you know about the Concert recruiting. DH's neurologist asked if we'd be interested in the clinical trial at UCLA, I've tried to read about it, but you're the fountain of information. Thanks! Di
Concert is (or was on Wednesday of last week) recruiting at Duke. My DH was on open label and I think doing a little better in some areas or at least holding his own. Then Medivation/Pfizer took that away. I tried to enroll him with Concert at Duke but couldn't because he had already been in the other trial. Anyone in the Durham, NC area that might be interested might need to apply soon.
Hi, Blossom. CONCERT is the one trial that Pfizer intends to keep going. It's for mild- to moderate-AD, so if it is successful, Pfizer will be able to apply for approval from the FDA. It requires that the ADLO be on a stable dose of Aricept (only). Twelve-month double-blind, placebo-controlled study, with one third of patients getting placebo, one-third getting a low dose of Dimebon, and one-third getting a high dose (i.e., the one we were on in the safety trial, which went very well.)
Estimated enrollment 1,050. I don't know how close they are to filling their quota -- enrollment could end at any time.
Inclusion Criteria:
* Mild-to-moderate Alzheimer's disease * Probable AD (DSM-IV-TR) * MMSE score between 12 and 24, inclusive * Stable on donepezil for at least 6 months
Exclusion Criteria:
* Other causes of dementia * Major structural brain disease * Unstable medical condition or significant hepatic or renal disease