By Harris Meyer | KHN
The Food and Drug Administrations decision next week whether to approve the first treatment for Alzheimers disease highlights a deep division over the drugs benefits as well as criticism about the integrity of the FDA approval process.
A lot is riding on the drug for Biogen. It is projected to carry a $50,000- a-year price tag and would be worth billions of dollars in revenue to the Cambridge, Massachusetts, company.
The FDA is under pressure because an estimated 6 million Americans are diagnosed with Alzheimers, a debilitating and ultimately fatal form of dementia, and there are no drugs on the market to treat the underlying disease. Although some drugs slightly mitigate symptoms, patients and their families are desperate for a medication that even modestly slows its progression.
Aducanumab helps the body produce antibodies that remove amyloid plaques from the brain, which has been associated with Alzheimers. Its designed for patients with mild-to-moderate cognitive decline from Alzheimers, of which there are an estimated 2 million Americans. But its not clear whether eliminating the plaque improves brain function in Alzheimers patients. So far, nearly two dozen drugs based on the so-called amyloid hypothesis have failed in clinical trials.
Besides questions about whether the drug works, there also are safety issues. More than one-third of patients in one of the trials experienced brain swelling and nearly 20% had brain bleeding, though those symptoms generally were mild and controllable. Because of those risks, patients receiving aducanumab have to undergo regular brain monitoring through expensive PET scans and MRI tests.
Some physicians who treat Alzheimers patients say they wont prescribe the drug even if its approved.
Theres a lot of hope among my patients that this is going to be a game changer, said Dr. Matthew Schrag, an assistant professor of neurology at Vanderbilt University. But the cognitive benefits of this drug are quite small, we dont know the long-term safety risks, and there will be a lot of practical issues in deploying this therapy. We have to wait until were certain were doing the right thing for patients.
A joint briefing document strikes me as completely inappropriate and an abdication of the FDAs claim to being the best regulatory agency in the world, Lurie said.
The FDA and Biogen declined to comment for this article.
But the association has drawn criticism for having its representatives testify before the FDA in support of the drug without disclosing that it received $525,000 in contributions last year from Biogen and its partner company, Eisai, and hundreds of thousands of dollars more in previous years. Other people who testified stated upfront whether or not they had financial conflicts.
Dr. Leslie Norins, founder of a group called Alzheimers Germ Quest that supports research, said the lack of disclosure hurts the Alzheimers Associations credibility. When the association asks the FDA to approve a drug, shouldnt it have to reveal that it received millions of dollars from the drug company? he asked.
But Joanne Pike, the Alzheimers Associations chief strategy officer, who testified before the FDA advisory committee about aducanumab without disclosing the contributions, denied that the association was hiding anything or that it supported the drugs approval because of the drugmakers money. Anyone can search the associations website to find all corporate contributions, she said in an interview.
Pike said her association backs the drugs approval because its potential to slow patients cognitive and functional decline offers substantial benefits to patients and their caregivers, its side effects are manageable, and it will spur the development of other, more effective Alzheimers treatments.
History has shown that approvals of first drugs in a category benefit people because they invigorate the pipeline, she said. The first drug is a start, and the second and third and fourth treatment could do even better.
Lurie disputed that. He said lowering the FDAs standards and approving an ineffective or marginally effective drug merely encourages other manufacturers to develop similar, me too drugs that also dont work well.
The Public Citizen Health Research Group, which opposes approval of aducanumab, has called for an investigation of the FDAs unprecedented and inappropriate close collaboration with Biogen. It asked the inspector general of the Department of Health and Human Services to probe the approval process, which that office said it would consider.
Woodcock refused, saying in a letter that FDA interactions with drugmakers make drug development more efficient and more effective and do not interfere with the FDAs independent perspective.
Although it would be unusual for the FDA to approve a drug after rejection by an FDA advisory committee, its not unprecedented, Lurie said. Alternatively, the agency could approve it on a restricted basis, limiting it to a segment of the Alzheimers patient population and/or requiring Biogen to monitor patients.
That will be tempting but shouldnt be the way the problem is solved, he said. If the product doesnt work, it doesnt work. Once its on the market, its very difficult to get it off.
If the drug is approved, Alzheimers patients and their families will have to make a difficult calculation, balancing the limited potential benefits with proven safety issues.
Mike was having brain bleeds anyway, and I wouldnt have risked him having any more side effects, with no sure positive outcome, said Saint, who lives in Franklin, Tennessee. It sounds like maybe that drugs not going to work, for a lot of money.
Their adult daughter, Sarah Riley Saint, feels differently. If this is the only hope, why not try it and see if it helps? she said.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.