ODAC Votes Against Safety Profile of Secura Bio’s P13K Inhibitor (Updated)
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In an 8-4 vote, the FDA’s Oncologic Drugs Advisory Committee Roster voted against the benefit-risk profile of Secura Bio’s P13K inhibitor Copiktra (duvelisib).
After hours of debating updated overall survival data for Copiktra and safety and tolerability concerns, the committee cast the votes that will likely signal the removal of Copiktra from the U.S. market.
BioSpace reached out to Secura Bio Monday morning but has not yet received a response.
The committee was asked to determine if the benefit-risk profile of duvelisib was favorable in patients with relapsed or refractory CLL or SLL after at least two prior therapies. The answer, according to the committee, was largely no.
“This is an efficacious drug, but I don’t think it met the bar of safety,” Dr. Andrew Chen, a temporary member of ODAC, said after casting his vote.
Chen’s worry was joined by other committee members who raised concerns about the safety profile of Copiktra. Dr. Christopher Liu, an associate professor of Medicine at the University of Colorado Cancer Center, said he has concerns about the P13K class and its noted toxicity issues.
“If we’re not clearly improving overall survival in our patients and increasing toxicity in associated death, I don’t know if we’re helping our patients,” he said.
Throughout the meeting, the committee members noted the efficacy of Copiktra. Despite the efficacy, the committee largely believed the benefits did not outweigh the risks when compared to the adverse events associated with the drug.
The P13k class, many of which were greenlit based on single-arm studies, are being closely re-examined by the FDA due to safety concerns. Earlier this year, an FDA advisory committee overwhelmingly recommended halting single-arm clinical studies of PI3K inhibitors due to those toxicity worries.
Copiktra, which Boston-based Verastem initially developed, was granted full approval by the FDA in 2018. The long-term follow-up data reviewed by ODAC suggested that Copiktra did not provide longer life to patients when equated to the Novartis comparator drug Arzerra.
In its briefing documents released ahead of the meeting, the FDA honed in on Copiktra’s concerning safety data. The FDA wrote that duvelisib is “associated with substantial toxicity that includes fatal or serious infection, diarrhea or colitis, rash, pneumonitis, hepatotoxicity, and neutropenia.”
Data from the DUO trial revealed that patients treated with duvelisib experienced higher rates of adverse and serious adverse events. Twenty-three of the patients, or about 15% who received Copiktra, died.
Liu said that the rate of death data is concerning. He said the percentage of patients who died was not insignificant and called it “an incredibly high cost” for treatment.
The FDA noted that other safety data from the study showed that 124 patients treated with Copiktra, about 78% of the patient population, faced serious adverse events. In the AstraZeneca arm, only 50 patients, about 32%, suffered serious adverse events. Seventy patients received Copiktra discontinued treatment, and 48 saw their dosing levels reduced.
David Harrington, emeritus professor of Biostatistics at the Harvard T.H. Chan School of Public Health and Dana-Farber Cancer Institute, noted in his dissenting vote that it was incumbent upon Secura Bio to establish a favorable profile for Copiktra.
“Given the current context and data about this class and the extended follow-up on this study, I don’t think they’ve established that,” he said.
Liu agreed and said he is sure that there are patients who received Copiktra as a treatment for their cancer and are now alive and well because of that medication.
“But the flip side is also true, that patients have passed away because of this medication. It’s not just about offering treatment options but also the cost in terms of toxicity and death,” Liu added.
In a statement sent to BioSpace, Secura Bio said it continues to believe Copiktra should remain on the market as a viable option for CLL patients.
"These patients have very few therapeutic options after those therapies fail and have a poor prognosis. Copiktra represents a real chance for them to further treat their illness and it would be a great disservice to not make this product available to them," the company said in a statement. "We continue to believe that Copiktra should remain as a viable option for these desperate patients and will continue to advocate for them and the CLL community at large."