In June, the FDA gave conditional approval to a treatment for Alzheimer’s Disease (AD), aducanumab, trade name Aduhelm. It’s an IV anti-amyloid monoclonal antibody therapy. Over the last several years, it had rejected similar agents.
AlzheimerGadfly will provide links below to some of the controversy that has ensued. Concerns have been raised about scientific rigor and possible illegal influences in the decision, so that the FDA itself has launched an investigation. The company and the FDA leaders involved have made their own statements about the process.
Some medical centers are choosing to not even offer the drug, most prominently the entire VA Health System, but others include Mt. Sinai in NYC and the Cleveland Clinic.
The approval was announced by a subgroup of FDA leadership, over the objections of the relevant Advisory Committee of experts, resulting in several of those experts resigning.
On the academic side, a NEJM Perspective piece (July 28) was written by members of that Advisory Committee outlining their objections in some detail. Based on the science presented by the company, they call the clinical impact “highly uncertain.” They also say…”Beta-amyloid may represent an epiphenomenon but not directly cause Alzheimer’s disease.” They consider the investigation appropriate.
On the personal side, Dr. Dan Gibbs, an academic neurologist who has AD and was a study subject in an aducanumab trial, was interviewed by the Boston Globe (July 31). [might be behind a paywall] The medication put him in the ICU with brain swelling, one of the known side effects. He was a co-author of the case report of his own experience.
On the other hand, he says his brain seems “sharper” after the experience, although he says that might be because of another drug, Aricept. He did also receive IV steroids in the ICU amongst other medications. The case report does mention that his neuropsychological testing one year after the ARIA episode showed decline.
In the newspaper piece, he was “surprised” with the way Aduhelm was approved; he had wanted further trials and feels that the dangers were being dismissed. He recognizes that Aduhelm’s use going forward will be a “difficult question.”
On the company’s side, Dr. Alfred Sandrock, head of Biogen’s Research and Development, posted an open letter which mentions “misinformation and misunderstanding” of the agent.
On the FDA’s side, Dr. Patrizia Cavazzoni and her colleagues had an opinion piece in the Washington Post about their rationale behind the decision to approve. They mention that they had a focus group of people with dementia, and caregivers who seemed to want a drug, even with uncertainty about its efficacy. However, acting FDA Commissioner Dr. Janet Woodcock, in a tweet (?!?) asked for an independent investigation into the matter (July 9).
On the Public Citizen watchdog side, Dr. Michael Carome and the non-profit group have been vocal (or have written) about needing an investigation even before the approval (last year Dec 9) because of what they saw as Biogen’s influence on the process, and has called for resignations of FDA leaders over the approval.
On the speculation side, the original FDA indication wording was fairly broad, but is now tightened down toward early stage patients. However, commenting on some of the advertising, one would think that everyone needs a little Aduhelm at some point! Baltimore Sun Op-Ed July 9 “Do we all have Alzheimer’s? Drug makers might want you to think so”
On the business side, WSJ reported (Aug 12) that the VA Health system won’t cover Aduhelm (article behind a paywall). Yahoo finance says that 300 hundred American centers so far have been approved to administer the drug (out of 900), but they expect more. Medicare approval is evidently still pending (Aug), and some insurers won’t cover it, creating a dilemma for some because the projected cost is >$50K. The agent does not claim to be a cure.
