The underside of the approval of aducanumab, an immunotherapy that clears amyloid-β from the brain, is very much a textbook case of regulatory capture. While the treatment does clear amyloid-β, it doesn't help patients all that much. Benefits observed in trials were marginal to the point of non-existence. The arm-wrestling under the hood has nothing to do with the welfare of patients and everything to do with maintenance of bureaucracy and control for the sake of bureaucracy and control on one side versus rent seeking on the other. An ugly business.
The silver lining is that now it will be easier to work on combination therapies that remove amyloid-β and address other issues. Amyloid-β is either a side-effect of the development of Alzheimer's disease, or one of several important mechanisms, most or all of which must be meaningfully addressed in order to help patients. It is hard to make progress in the latter scenario if regulators insist on only testing one thing at a time, and also have an efficacy bar for approval.
The regulatory system is dramatically broken. Absent regulators, it would cost a tenth as much as it does now, or less, to prove out new therapies in human volunteers. For most medicines, there really isn't a sizable practical difference between the over the top rigor of GMP manufacture and ordinary, sensible quality control on a batch by batch basis. The enormous cost imposed by the the FDA process really isn't essential to producing safe medicines, or to testing efficacy. Yet here we are, in a world in which progress is glacial because the powers that be have decided that pursuing the unattainable goal of zero risk is worth any cost in lives and funding, and the population at large never sees the medical progress that would have taken place absent the regulators.
Today FDA approved Aduhelm (aducanumab) to treat patients with Alzheimer's disease using the Accelerated Approval pathway, under which the FDA approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug's clinical benefit.
We are well-aware of the attention surrounding this approval. We understand that Aduhelm has garnered the attention of the press, the Alzheimer's patient community, our elected officials, and other interested stakeholders. The late-stage development program for Aduhelm consisted of two phase 3 clinical trials. One study met the primary endpoint, showing reduction in clinical decline. The second trial did not meet the primary endpoint. In all studies in which it was evaluated, however, Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion. It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline.
We know that the Peripheral and Central Nervous System Drugs Advisory Committee, which convened in November 2020 to review the clinical trial data and discuss the evidence supporting the Aduhelm application, did not agree that it was reasonable to consider the clinical benefit of the one successful trial as the primary evidence supporting approval. As mentioned above, treatment with Aduhelm was clearly shown in all trials to substantially reduce amyloid beta plaques. This reduction in plaques is reasonably likely to result in clinical benefit. After the Advisory Committee provided its feedback, our review and deliberations continued, and we decided that the evidence presented in the Aduhelm application met the standard for Accelerated Approval.
The need for treatments is urgent: right now, more than 6 million Americans are living with Alzheimer's disease and this number is expected to grow as the population ages. Alzheimer's is the sixth leading cause of death in the United States. Although the Aduhelm data are complicated with respect to its clinical benefits, FDA has determined that there is substantial evidence that Aduhelm reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients.