In June 2021, the US Food and Drug Administration (FDA) approved Biogen’s new Alzheimer’s Disease Aduhelm against the opinion of its own advisory committee, raising concerns among researchers and dementia patient advocates.
The FDA green-lit Aduhelm using their “Accelerated Approval” process, which allows the agency to approve drugs based on their performance on surrogate markers. Surrogate markers are metrics that are not generally meaningful on their own, but correlate with clinical benefits that matter to patients. In the case of Aduhelm, the drug did not meaningfully improve patients’ ratings on a clinical dementia scale, but it did reduce amyloid plaques in the brain, which are associated with Alzheimer’s Disease.
The accelerated approval pathway is meant to help get treatments for life-threatening diseases on the market more quickly. However, research has shown that this process is often abused when it comes to cancer drug approvals. Most cancer drugs approved through this process don’t show meaningful results in later clinical trials and surrogate markers for new cancer drugs are often used without being vetted. While manufacturers are required to conduct a post-marketing clinical trial to prove effectiveness on a clinically meaningful outcome, these typically take years to publish (if the studies are ever conducted at all).
The approval of Aduhelm has brought many of these issues into the spotlight, leading to new legislative proposals. One of these proposed bills, called the Accelerating Approval Integrity Act of 2022, would add new requirements for drug companies to ensure that post-approval studies are conducted in a timely way. The Act would require these studies to be designed before approval and could require companies to start these trials at the time of approval. If the studies are not conducted “with due diligence” or if they do not find a clinical benefit, there could be fines for drug companies and their drug approval would be withdrawn.
These commonsense changes would go a long way toward achieving the intended purpose of the accelerated approval pathway. However, another piece of proposed legislation, the “Accelerating Access for Patients Act of 2022,” warrants attention as well. This bill would broaden the accelerated approval pathway to take into account the “severity, rarity, or prevalence of the disease or condition and the availability or lack of alternative treatments” when evaluating the effectiveness and safety of new drugs.
This seems like an important consideration to make, as patients suffering from terminal illnesses like ALS likely have different risk-benefit considerations than do patients with less severe illnesses. However, exceptions made in order to give patients the “right to try” or “provide hope” for those with fatal conditions seems to be partly what got us into the Aduhelm mess in the first place. Any legislation proposed to broaden the already fairly-lenient accelerated approval pathway should not be taken lightly.