FDA adcomm votes narrowly against Veru's Covid drug, citing uncertainties amid mortality benefit in small trial
The FDA’s Pulmonary-Allergy Drugs Advisory Committee on Wednesday voted 8-5 against Veru’s repurposed cancer drug, sabizabulin, as a treatment for certain hospitalized adults with Covid-19, arguing the benefits do not outweigh the risks.
The vote against Veru’s drug followed a close dissection of the pivotal randomized, double-blind, placebo-controlled clinical trial for sabizabulin in 204 patients hospitalized with Covid-19, which was stopped early due to efficacy and showed a strong mortality benefit.
Adcomm panelist Daniel Gillen of the University of California, Irvine voted against sabizabulin’s benefit-risk profile as he said there is limited safety and efficacy data, without a full understanding of the mechanism of action. Panelist Janet Lee of the University of Pittsburgh School of Medicine voted against and said she would like to see a new trial design.
FDA reviewers at the meeting pointed to a list of potential uncertainties around the mechanism of action, trial design, small sample size, standard of care differences between trial arms, and more. But they also noted some clear positives, like the strength of the primary endpoint, and that the bar for an EUA is significantly lower than a full approval.
“In the face of an ongoing pandemic, a survival benefit is difficult to discount,” FDA division deputy director Banu Karimi-Shah said ahead of the vote. “And certainly all-cause mortality is an important and clinically meaningful endpoint.”
Despite some qualms, FDA staff at the meeting said they’re considering an EUA with a requirement for another RCT in the same population as a condition of the authorization.
The adcomm members generally offered support, with some qualms, on the pivotal data, although they questioned the lack of an adequately-sized safety database, who the optimal population to receive the drug is, and when exactly to administer it.
On the safety side, panelist Lindsey Baden of Dana-Farber Cancer Institute (who voted in favor of the drug) said his level of concern is “through the roof, very high” even for common adverse events, but “in relation to the outcome of greatest concern,” which is mortality, he said he’s less concerned. “If the mortality benefit were substantially lower, then this becomes a greater concern,” he said.
Adcomm panelist Edwin Kim, associate professor at the University of North Carolina School of Medicine, voted for the drug and said the mortality data are impressive. Others noted that the effect seen in the trial is clinically meaningful and large.
But Pamela Shaw of the biostatistics division at the Kaiser Permanente Washington Health Research Institute questioned what the rush is to get sabizabulin onto the market before another trial can be conducted for, at the very least, a more robust safety database.
The FDA does not have to follow the advice of its adcomm votes, but it often does.
Meanwhile, as the meeting was ongoing, the FDA on Wednesday announced a new EUA for Swedish Orphan Biovitrum AB’s (Sobi) Kineret (anakinra) as a repurposed treatment for Covid-19 in certain hospitalized patients.