Stunning reversals, surprise delays and controversial approvals are the order of the day at the FDA lately—and doctors have had enough.
Physicians’ trust in the agency is plummeting, according to a recent survey by Spherix Global Insights. More than 40% of the doctors surveyed said their confidence in the FDA has dropped over the past year
Doctors cited a range of problems—including suspected political motivations and lack of transparency—as frustrating pain points in the July survey of 252 specialty nephrologists, neurologists, dermatologists, rheumatologists and gastroenterologists.
“It wasn’t so much the specialists feeling that the FDA was being too aggressive or too lax, but just erratic,” Spherix President Jennifer Robinson said. “In the past, if a company hit all their endpoints and nothing funky came out of the clinical trial—and the trial was designed in conjunction with the FDA—we were pretty much expecting an approval."
Disappointed neurologists and nephrologists are leading the decline, flummoxed by both Biogen Alzheimer’s drug approval despite an expert advisory committee’s decisive no vote and the surprise rejection of Ardelyx’s tenapanor in chronic kidney disease.
Neurologists are particularly discouraged—84% have lost confidence in the FDA over the past year, Spherix found. The controversial approval of Biogen’s Aduhelm in June is the key culprit; 82% of neurologists disagreed with the FDA nod. However, neurologists also questioned the FDA's surprise rejection for Acadia’s Nuplazid to treat hallucinations in dementia-related psychosis.
One neurologist summed up many of the Aduhelm comments in describing the diminished trust in the FDA.
“The erosion is based on the disastrously bad decision to approve aducanumab, which seems like a poorly developed and even possibly corrupt decision," the doctor said. "I cannot remember a similar situation in which there was so much dismay and disbelief created by an FDA decision. We do not plan to use aducanumab at this time and we no longer know what to think about and how much to trust any future FDA decisions."
Another hot topic for specialists is the JAK inhibitor class. Beginning with the FDA's rejection of Gilead’s filgotinib in rheumatoid arthritis last August, JAK inhibitors have been having a tough go. AbbVie’s Rinvoq, Eli Lilly and Incyte’s Olumiant, and Pfizer’s abrocitinib are all sitting in a holding pattern as the FDA scrutinizes Xeljanz’s post-market safety study and holds up new approvals across the whole JAK class.
Rheumatologists and dermatologists agree that it’s OK to scrutinize the class. But the specialists question why the FDA is holding up three JAK meds in atopic dermatitis, plus applications for Rinvoq and Xeljanz in rheumatology, based on a high-risk patient trial for one drug—Xeljanz, Spherix's Lynn Price, VP of strategy and innovation, said.
More than two-thirds of rheumatologists and dermatologists believe the FDA should focus on each individual JAK and its own studies, she said.
Robinson added, “The transparency really rang through with autoimmune specialists, who said, ‘Just tell us why and give us a timeline. When we can expect this and what is the hold-up?’”
The main theme from the Spherix study is the unpredictability of the FDA—and doctors are left wondering why. Some pointed to biases and politics and the possibility that the COVID-19 pandemic is wreaking more havoc inside the FDA than it’s letting on.
Still, no matter the reason, the result is a slower uptake of drugs and a cautious physician population.
So cautious, in fact, doctors told Spherix they plan to go it alone. Many told Spherix they will read and interpret trial data for themselves, wait for medical conferences to hear trial data presented directly by researchers, or simply delay prescribing a new drug until real-world evidence accumulates.
Analysts are wondering what’s going on as well. Piper Sandler put out a note this week detailing the Spherix data and asking its own questions.
Its number-crunching analysis shows that the FDA's big picture remains relatively stable, with this year's number of rejections and approvals on par with previous years. However, that hasn’t stopped the handful of surprise FDA jabs from knocking the industry for a bit of a loop.
“We think FDA inconsistencies provide a key explanation for the sector's recent underperformance,” Piper said, adding “while the numbers may indicate things are more consistent than perceived, we think perception matters quite a lot here.”
What’s next? That’s likely up to the FDA.
"We've really seen the pendulum go back and forth decision by decision based on feedback that they're getting—Aduhelm has been such a black eye," Robinson said.
As Piper noted, the next high-profile approvals on deck—BioMarin’s delayed vosoritide for children with achondroplasia now set for November and Akebia Therapeutics’ vadadustat in March 2022—are at “higher risk now.”
Its final sentiment: “The next few high-profile regulatory decisions will be critical not just for the investability of biotech, but for nothing less than the preservation of physicians' trust in FDA."