$BHVN

@adamfeuersteinNov 5, 2025 · 12:17 PM

$BHVN approval was a coin flip at best, so the CRL and the reasons for it are not really a surprise. $QURE is different in some ways. This is what I wrote on Oct. 9 We should learn something about regulatory flexibility under the current FDA leadership when the agency renders a decision in mid-November on Biohaven Pharmaceuticals’ treatment for spinocerebellar ataxia (SCA), a rare and debilitating neurodegenerative disease. “This is a really tough call. I’d say approval is a 50-50 shot, at best,” a Biohaven shareholder told me. I heard the same toss-up sentiment from other shareholders as well, reflecting uncertainty that seems to precede so many FDA decisions these days, exacerbated by Biohaven’s controversial data package. In May, the FDA extended the decision date for the Biohaven drug, called troriluzole, by three months in order to review “recent submissions related to information requests from the FDA,” the company said. Then in August, the FDA told Biohaven that a previously planned (but not yet scheduled) advisory committee meeting to review troriluzole was “no longer needed for regulatory decision making.” Canceling an advisory committee meeting is often a negative indicator, as we saw recently with Capricor Therapeutics and its cell therapy for Duchenne muscular dystrophy. But troriluzole was submitted to the FDA’s Center for Drug Evaluation and Research, or CDER. Its leader, George Tidmarsh, has said publicly that advisory committee meetings are often unnecessary and their use should be reduced, agency wide. Under the CDER umbrella, troriluzole is being reviewed by the Division of Neurology I within the Office of Neuroscience — a group that has a history of approving drugs with messy data, like Aduhelm and Skyclarys. It’s also been stable, personnel-wise, even with all the FDA staff turnover. When it comes to drugs for rare diseases, clinical data may not matter as much as they do in other cases, as we saw recently with the approval of a drug for Barth syndrome for Stealth BioTherapeutics. In that case, a decision made by FDA review staff to reject the drug was overturned by a senior agency leader. I wrote about troriluzole in this newsletter in September 2024, making the point that its data package was going to test the agency’s appetite for regulatory flexibility. Biohaven’s submission is supported by a Phase 3 study in which troriluzole delayed the progression of SCA by 50% after three years, representing a 1.5-year treatment gain. The comparator arm in this “real world” study was not a placebo, but a carefully selected group of untreated SCA patients enrolled in an external, natural history study of the disease. The study results were announced in September 2024, and at that time, Biohaven said it had worked with the FDA on the design of the study to ensure that the external control patients closely matched those in the treatment arm, bolstering the validity of the results. Drug companies commonly assure us that the FDA is on board with whatever they’re doing. The truth is often something different. The troriluzole situation is muddled further because the FDA is now run by officials with very different perspectives than their predecessors. One more wrinkle: Before it had real-world comparison data, Biohaven ran a true, placebo-controlled study. It failed. The company submitted for approval anyway, and the FDA turned away the application without review. Biohaven hasn’t disclosed a specific FDA decision date, but it should come the week of Nov. 10, based on previous disclosures.

@adamfeuersteinNov 5, 2025 · 12:10 PM

@GyroMac Prasad not involved in the $BHVN review.

@adamfeuersteinNov 5, 2025 · 11:41 AM

$QURE $BHVN The question I (we) now struggle to understand: Is the "new" FDA now uniformly opposed to using external /historical controls in drug applications? Or Were there significant / insurmountable flaws in these specific uses of ECs that led to the FDA decisions?

@adamfeuersteinNov 5, 2025 · 1:36 AM

$BHVN rejection https://t.co/h0TFXkDyk1

@adamfeuersteinOct 9, 2025 · 5:31 PM

The limits of FDA flexibility are tested as a controversial Biohaven $BHVN drug decision nears https://t.co/MaqnNoshrV

@adamfeuersteinSep 25, 2025 · 7:11 PM

@avidresearch I don't know anything about the $BHVN external control or how it was constructed, so I can't comment. $QURE is sourcing its ECA from a very large, independent and well-regarded natural history study, which works in its favor, I think. Legit, even if doesn't entirely eliminate the risks. On the other side of the spectrum, toally illegitimate, for instance, you have a company like $NWBO that made up its own ECA AFTER knowing its drug failed and then cherry-picked studies to fake a positive result. Pure garbage. ECAs remain controversial. Hopefully we learn something from $BHVN and $QURE.