The U.S. Food and Drug Administration (F.D.A.) has been under fire again after approving the drug Relyvrio to treat patients with amyotrophic lateral sclerosis (ALS) last month. Also called Lou Gehrig’s Disease, ALS is a rare, progressive disease that deteriorates voluntary muscle movement, ultimately resulting in death. It has no cure. However, this new drug lacks strong evidence for its efficacy.
Which mistake would you rather make?
The controversy stems from the lack of strong evidence regarding Relyvrio’s effectiveness. Despite a lack of sufficient support that the drug can extend patients’ lives or slow the rate of deterioration according to their own reviewers, the F.D.A. granted the drug Priority Review and orphan drug designation at the end of last month.
The reasoning behind this decision has to do with a complex bioethical question – if there is the potential to treat a previously untreatable disease with a new pharmaceutical, but the consequences are unknown, do you prescribe the drug? Is the unknown enough to deny patients hope? In this case, the F.D.A. says the uncertainty is acceptable.
This move comes after patient advocacy groups and physicians had been pushing for approval, securing funding through the viral “Ice Bucket Challenge,” and writing letters to the F.D.A and testifying before their advisory committee. One of the physicians who signed the letter summed up the emotions behind the push for drug approval.
“In your difficult job, there’s always going to be a chance of making a mistake; it comes down to which mistake you would rather make…Can you imagine the mistake of saying no and then getting confirmatory evidence in two years that this really did work? And realizing all those patients were much more disabled or even dead when they didn’t need to be? I don’t know how you’ll be able to live with yourself if you make that mistake.”
– Dr. Richard Bedlack to the New York Times
A.L.S., Alzheimer’s, and Aduhelm
Critics, however, say approval of Relyvrio is yet another point in a concerning trend. The obvious comparison is to Aduhelm. Back in 2021, the F.D.A. approved the drug Aduhelm to treat Alzheimer’s in a move similar to this latest one. With limited evidence of effectiveness, Aduhelm sped through accelerated approval due to the serious and life-threatening nature of the disease it was supposed to treat. Some patient advocates and physicians rejoiced, taking more issue with the absurdly high price for the treatment than with its questionable efficacy. Others protested the decision, and the Centers for Medicare & Medicaid Services (CMS) refused to cover the drug until it was proven effective in a clinical trial. Aduhelm took another blow months later when it was revealed the research that served as the primary basis for the theory of treatment had been fabricated, calling into question our entire understanding of Alzheimer’s and its development.
There are key differences that distinguish Relyvrio from Aduhelm. Whereas Aduhelm had concerning side effects, Relyvrio was shown to be safe in its trial. Alzheimer’s is also much more common than ALS, meaning that Aduhelm was far more likely to raise Medicare premiums. Still, the high price tag of the still-unproven Relyvrio is controversial – drug pricing this high inevitably impacts us all.
Evidence-based medicine is harder than it sounds
Every physician and scientist strives to make evidence-based decisions. But in the case of Relyvrio, as with Aduhelm, the evidence is unclear and does not justify the high price. An additional factor is the long process for fixing mistakes. Removing drugs from the market takes years – as evidenced by the fight to remove the pregnancy drug Makena from the market – allowing patients across the nation to be exposed to potentially dangerous drugs. Consequences can range from biological, in which someone has bodily harm from a bad drug, to financial, in which a patient bankrupts themselves for a drug that doesn’t work.
Some policy action is being taken to remedy this situation. The Accelerated Approval Integrity Act outlines new authority and guidelines for the F.D.A., like outlining expedited procedures for withdrawing approval for drugs that don’t show efficacy in later trials. Given the controversy and nuance in the debate around drug development and sales, it’s clear that we need a better process for determining what exactly is required when we say “evidence-based medicine.”