A Dubious Eye Cast on FDA Accelerated Approval

It’s more than just a matter of time.

I have discussed many times on Monitor Mondays the controversial Food and Drug Administration (FDA) accelerated approval of Aduhelm, the intravenous medication for Alzheimer’s dementia – and the correct decision by the Centers for Medicare & Medicaid Services (CMS) to only cover the medication in clinical trials.

Well, last week trial results were released for another drug, lecanemab, in the same class, and also seeking FDA accelerated approval. And as with Aduhelm, there was significant improvement in amyloid plaque in the brain, but the clinical improvement, while statistically significant, was not clinically significant, with a difference of 0.45 on an 18-point scale.

Now, will more time show more clinical improvement? We all hope so, but it is too early to say. Also of note was that two patients who received the medication died from brain hemorrhage. It will be interesting to see the FDA review results, and ultimately the CMS decision on this drug.

Speaking of accelerated approval, as a reminder, there is an FDA program for important drugs to be provisionally approved while awaiting definitive studies. Well, last week a drug approved under accelerated approval was withdrawn from the market. The drug, Sulfamylon, is used for treatment of burns. Now, a drug withdrawal is not unusual, but this case is. The drug was approved under accelerated approval in 1998, and now, 24 years later, the drug company determined that they cannot afford the trial required to get full approval. Yep: for 24 years, the FDA allowed an unproven medication to be used. One has to wonder about a system that allows this to happen.

Last week also saw the publication of a study looking at the effectiveness of spinal cord stimulators for chronic pain. In this trial of patients with past lumbar surgery, every patient was treated with the standard of having a trial period prior to the actual implantation, and every patient that had benefit had the device implanted. But then the stimulators were programmed to either give the proper cord stimulation or stimulation at a frequency that can best be described as a placebo. And the pain relief experienced by both groups appeared to be equal. Of course, this was not a definitive study, and limited to a small subset of patients with chronic lumbar pain, but it should lead to a careful analysis to determine for whom these devices truly add benefit.

Next, some of you may have heard that the mayor of New York City is directing police and healthcare workers to hospitalize unhoused mentally ill patients involuntarily, even if they do not pose a risk to themselves or others.

Now, of course, this has huge legal, ethical, and financial implications, but I won’t address those – but rather point out that I doubt any hospital in New York City, or the country has the capacity and resources to care for these patients. In fact, the access to inpatient psychiatric care for patients is currently at an unsustainably low level.

Now, is this a welcome first step by a government to address the issue of the unhoused that was simply not well thought-out? Time will tell. I do not think anyone would disagree that more resources are necessary to address the social determinants of health (SDoH).

Programming note: Listen to Dr. Ronald Hirsch as he makes his rounds every Monday on Monitor Mondays and sponsored by R1 Physician Advisor Solutions.