A biotechnology company’s plans to file for Food and Drug Administration approval of a drug to treat Alzheimer’s disease despite ending its clinical trial program following a futility analysis have drawn some harsh words from an investment bank analyst.
Cambridge, Massachusetts-based Biogen surprised many when it said in October it would seek FDA approval for the drug aducanumab in early 2020, based on a consultation with the agency following an analysis of a larger data set from its Phase III EMERGE and ENGAGE studies. The company said the new analysis showed EMERGE in particular had met its primary endpoint despite having discontinued both trials in March after a futility analysis indicated they would fail. The earlier announcement added to what were already growing doubts about the amyloid beta hypothesis, the idea that it’s possible to treat Alzheimer’s by targeting the amyloid beta plaques that are characteristic of the disease.
But in a note to investors Monday, Baird analyst Brian Skorney slammed the company’s decision. “Aducanumab is not getting approved absent a Deus ex Machina,” he wrote. “The preponderance of the data indicates aducanumab doesn’t provide a clinical benefit.”
Based on the data, even running another clinical trial would send the company’s share value down, Skorney wrote – and the threshold for regulatory approval is higher.
“The bottom line is, the FDA standard of approval is substantial evidence of efficacy, and the cumulative data for aducanumab falls really far short of this standard to anyone but the most ardent GOOP subscribers,” he wrote, referring to actress Gwyneth Paltrow’s health-and-wellness brand, which health experts have criticized for promoting pseudoscience.
Shares of Biogen were down 2.5% on the Nasdaq Monday afternoon. A company spokesperson declined to comment on the Baird note.
Skorney wrote that taken at face value, the results from EMERGE indicate the effect size of the drug is “negligible,” representing about 0.4 points on the Clinical Dementia Rating-Sum of Boxes scale over placebo over 78 weeks of treatment. While unmet medical need and societal interest in Alzheimer’s would probably be sufficient to “get [aducanumab] across the finish line, we don’t think it would be an easy road.”
And if history is a guide, it likewise indicates a rocky road ahead. Skorney noted that it’s not the first time a company has spoken positively about an FDA meeting for a controversial drug, only for it to turn out that the agency was negative. He cited the FDA’s 2016 rejection of BioMarin’s drisapersen and its rejection in August of Sarepta Therapeutics’ Vyodys 53 (golodirsen) for Duchenne muscular dystrophy – despite expressions of optimism by both companies’ executives – as examples. But he acknowledged the FDA could yet approve aducanumab.
“The people at FDA can make mistakes, succumb to noisy arguments, and relent in the face of political and/or public pressure,” he wrote. “There are a number of drugs on the market that we would not have approved if it were up to us, so there is certainly a plausibility that the FDA was warm and receptive to an aducanumab filing, despite what we see as the glaring deficiencies of the data.”
There are examples of the FDA appearing to cave to public pressure in approving a drug. Before it rejected golodirsen, the agency gave a controversial approval to Sarepta’s Exondys 51 (eteplirsen) for DMD. The approval in July of Karyopharm Therapeutics’ Xpovio (selinexor) for highly refractory multiple myeloma also drew criticism from doctors.
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