Otsuka and Lundbeck’s data are insufficient to establish significant efficacy of Rexulti plus sertraline in PTSD, according to the FDA’s outside experts.
An external panel of experts for the FDA voted strongly against Otsuka and Lundbeck’s proposed use of Rexulti, in combination with the selective serotonin reuptake inhibitor sertraline, for the treatment of post-traumatic stress disorder.
With a 10–1 split, the FDA’s Psychopharmacologic Drugs Advisory Committee on Friday flagged issues with the efficacy evidence backing the Rexulti regimen. Rajesh Narendran, professor of radiology and psychiatry at the University of Pittsburgh School of Medicine and a “no” vote, said that Otsuka and Lundbeck had not sufficiently shown that the Rexulti combo would be effective in this indication.
“One trial looked so promising and the other was trying to find something in [a] Phase II trial that could convince me that [the combo] could work,” he said. “It’s just another Phase III trial is what’s necessary.”
Brian Shiner, associate chief of staff for research at VA Vermont Healthcare System, agreed: “It’s just as likely that the drug does not work when added to sertraline as it does. So, I don’t think it’s worth the risk.” Shiner also voted against Otsuka and Lundbeck.
Only the patient advocate, retired clinical pharmacist Laura Block, voted in favor of Rexulti. In explaining her vote, Block pointed to accessibility and affordability issues that an approval could help with. “While both of these individual component drugs are on the market, a third-party payer isn’t likely to pay without an FDA-approved indication,” she explained.
For patients who aren’t able to afford to pay out-of-pocket, Block added, “I hate to think that they might have to wait another four years to see something happen.”
Still, Block conceded that there is a need for additional data to validate the clinical benefit of Rexulti plus sertraline in PTSD. “I do want to be certain that we don’t offer destructive false hope” to patients, she said. “I would love to see, no matter whether this is approved or not, either a Phase III or Phase IV study” to better characterize the efficacy of the Rexulti combo.
Rexulti is an atypical antipsychotic drug that is already approved for the treatment of schizophrenia and major depressive disorder. Otsuka and Lundbeck are proposing to combine Rexulti with sertraline for PTSD, for which they conducted two Phase III studies. One showed significant evidence of efficacy, while the other “was clearly and convincingly a negative study that did not demonstrate statistical significance on its primary or secondary endpoints,” according to an FDA briefing document released last week ahead of the advisory committee meeting.
The companies also submitted post-hoc data from a Phase II study, which detected a significant signal in favor of Rexulti and sertraline but was not enough to convince the FDA’s reviewers. “The retrospective selection of hypotheses and use of post hoc multiple testing procedures raises concerns about inflation of the overall Type I error [false positives] rate, which is crucial for demonstrating efficacy,” they wrote in the briefing document.
