Summary: There is a new emphasis on cooperative efforts to speed the development and approval of Alzheimer’s drugs. The difficulties in bringing new Alzheimer’s drugs to market, along with doubts about a cure, highlight the continued need for research on (and funding for) care.
I wrote in Part 1 of this post about the difficulties of getting new Alzheimer’s drugs to market. This problem is not entirely specific to Alzheimer’s – overall, new drug approvals are at a 25 year low.
For patients and families waiting for more effective treatments, it may seem like nothing is happening. But in reality, there are a lot of efforts underway to address this problem. Given tight funding, the difficulties of drug development, and the recent failure of several drugs in trial, there is a new emphasis on collaboration to bring Alzheimer’s treatments to market.
This second post is a brief review of the alphabet soup of organizations working together to try to develop new Alzheimer’s drugs and bring them market as quickly as possible.
The U.S. Food and Drug Administration (FDA) has responded to the decline in new drugs submitted to that agency for approval by launching several initiatives to speed both the development and approval of new drugs.
The agency’s Critical Path Initiative is a set of collaborations with other government agencies, universities and pharmaceutical companies. These collaborations involve providing the tools and training researchers need to use new technologies, along with discoveries in genetics, imaging and information systems, to improve the drug development process.
Other programs at the FDA focus on reducing the amount of time the agency takes to review new drugs submitted for approval:
- Fast Track – this process involves frequent communication and meetings between the FDA and the company requesting approval to make sure clinical trial design and data meet FDA guidelines and are unlikely to be roadblocks to approval. Fast Track is available when there is an unmet treatment need for a serious disease. New Alzheimer’s drugs that work differently from the drugs currently available would almost certainly fall into this category.
- Accelerated Approval – allows approval of new treatments based on surrogate endpoints or biomarkers. In the case of Alzheimer’s, that could mean using changes seen on brain scans or in spinal fluid as an indicator that a treatment is working. This would require evidence that these biomarker changes reflect changes in memory and thinking. With Accelerated Approval, actual effectiveness must be confirmed after approval for the drug to stay on the market.
- Priority Review – involves making more FDA resources available to reduce the target review time from ten months to six months. Priority Review is available for drugs that could significantly improve treatment.
From 2005 to 2009, the agency reduced the average time for review and approval of new drugs from 2.2 years to 1.2 years.
The Coalition Against Major Diseases (CAMD) is part of the Critical Path Institute, an organization that brings together scientists from government, universities and pharmaceutical companies to support the FDA’s Critical Path Initiative. CAMD focuses on Alzheimer’s, Parkinson’s and Huntington’s diseases and is working to validate biomarkers and standardize trial data to facilitate sharing. The Alzheimer Research Forum has published an excellent series of articles about CAMD’s work.
Government and nonprofits typically fund basic biomedical research. Pharmaceutical companies typically fund clinical trials. But according to Howard Fillit, there isn’t much funding available to translate basic research into human trials, and this slows the drug development process. Funding this “translational” work is the focus of the Alzheimer’s Drug Discovery Foundation (ADDF).
“We’ve cured rodents of Alzheimer’s pathology over 300 times now,” Dr. Fillit says. “But very few of these molecules get into human tests. What’s really needed is more translation of these studies into human testing. To complete preclinical testing on safety and toxicity, file an IND [Investigational New Drug] application with the FDA and conduct Phase 1 trials takes a few years and millions of dollars. But there’s a funding gap for this work. As a foundation, we are starting to fund more human testing to bridge that gap.”
Since its founding in 1998, the ADDF has funded $40 million in research on more than 300 potential drugs.
The U.S. National Institutes of Health recently proposed creating the National Center for Advancing Translational Sciences (NCATS). The Center would encourage collaboration and provide resources for translating basic research into new treatments. It’s not clear how the proposed Center would affect Alzheimer’s drug development. The Frequently Asked Questions section of the Center’s site says the center will also address medical devices and behavioral interventions, so it’s possible that the work there could speed development of new diagnostic or treatment devices as well as new methods of care for Alzheimer’s.
The Alzheimer’s Disease Cooperative Study (ADCS), funded by the National Institute on Aging, coordinates clinical trials of potential Alzheimer’s treatments that otherwise might not be developed by the pharmaceutical industry.
The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is also funded by the U.S. National Institute on Aging, as well as by pharmaceutical companies and charities. It is an effort to better understand progression of Mild Cognitive Impairment and Alzheimer’s, along with related biomarkers such as proteins in spinal fluid and structures seen on brain scans. The goal is to use information from ADNI to improve clinical trial design by standardizing biomarkers and ultimately reduce the time it takes to bring Alzheimer’s drugs to the market. ADNI GO extends the work of ADNI to study people with very early memory loss.
Alzheimer’s Prevention Initiative
The goal of the Alzheimer’s Prevention Initiative is to speed up trials of anti-amyloid drugs by testing them in people whose memory and thinking are currently normal, but who are at high risk of developing Alzheimer’s because of their age and genetic variations. The hope is that the participation of this high-risk group will reduce the time and expense of prevention research, and that these drugs will be effective in “pre-symptomatic” populations.
The Dominantly Inherited Alzheimer’s Network (DIAN), funded by the National Institute on Aging, is studying children whose parents had or have the rare genetic variations that guarantee they will develop Alzheimer’s. DIAN researchers are working to establish a research database and tissue repository for use by other researchers.
The Innovative Medicines Initiative (IMI) is a partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The IMI encourages and funds collaborative projects, including the PharmaCog project, which aims to pool data from previous clinical trials to develop tools to better predict which drugs in development are likely to be successful.
A new law, The National Alzheimer’s Project Act (NAPA), directs the Department of Health and Human Services to set up an office to develop a national plan to fight Alzheimer’s. There is currently no funding for this office.
Funded by the Alzheimer’s Association and Fondation Plan Alzheimer, the International Genomics of Alzheimer’s Project (IGAP) is a new collaborative effort among universities in the U.S., the U.K. and France to find all the genes contributing to Alzheimer’s disease.
An Alzheimer’s Cure?
So what does this alphabet soup of organizations, researchers and public/private partnerships mean to people with memory loss and their families? If the efforts are successful, more Alzheimer’s treatments will be developed, and at a faster rate. But even if new Alzheimer’s drugs are successful in trials, and approved by regulatory agencies, will Alzheimer’s be cured?
“I don’t think so,” says Howard Fillit. “Most chronic diseases, particularly those associated with old age, involve multiple pathways. We still haven’t cured heart disease, and cholesterol probably accounts for only 30% or so. We still don’t have a disease-modifying drug for diabetes, although insulin has been available for over 100 years. So this kind of science is incremental. Alzheimer’s disease is complex, and it will ultimately take a combination of prevention through lifestyle and comorbidity management plus therapeutics. The goal is to delay onset -- we won’t eliminate it.”
The difficulties in bringing new Alzheimer’s drugs to market, along with doubts about a cure, highlight the continued need for research on (and funding for) care.