The oncology division of the FDA has recently tightened regulations for expedited approvals and emphasised the significance of patient survival data. Several businesses promptly followed suit and withdrew questionable indicators when the agency applied more pressure. However, some businesses have made the decision to strike back.
The first-in-class blood cancer treatment Pepaxto from Oncopeptides and Secura Bio’s PI3K inhibitor Copiktra are the most recent two medications that will be examined at a forthcoming FDA consulting committee meeting because the manufacturers haven’t taken certain hints off the market despite warning signs from clinical trials.
According to an FDA filing, external experts will debate whether Pepaxto’s use in conjunction with dexamethasone for fifth-line therapy of multiple myeloma and Copiktra’s use in third-line chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) should continue.
The FDA has warned the public about the hazards associated with Pepaxto and Copiktra after the confirmatory studies for both medications revealed alarming indications of potential harm to patients’ lives.
Involuntarily withdrawing Pepaxto from the American market in October, Oncopeptides reversed the decision in January after doing new assessments of patient survival analysis from the phase 3 OCEAN research. Pepaxto marketing has been suspended by the company until a mutual understanding has been reached with the FDA.
When compared to Bristol Myers Squibb’s Pomalyst and dexamethasone in a cohort of patients with relapsed or refractory multiple myeloma after two to four lines of prior therapy, Pepaxto’s combination with dexamethasone was associated with a 10% increased risk of death in the original analysis of OCEAN data. Based on findings from the phase 2 HORIZON trial, which showed Pepaxto induced a 23.7% in a limited subset of patients who had had at least four prior lines of therapy, the peptide-drug combination initially earned its priority authorization last February.
The additional safety concerns raised by the overall PI3K inhibitor class for Copiktra had already attracted the FDA’s notice and were thoroughly examined at an advisory committee session in April. In third-line follicular lymphoma, Secura has already voluntarily discontinued Copiktra.
But Secura appears hesitant to give up easily in the broader CLL and SLL indications. Data from the phase 3 DUO study showed that Copiktra could prevent disease progression or death compared to Novartis’ Arzerra in patients who had undergone at least two prior lines of treatment. This led to Copiktra receiving the full third-line approval in 2018.
According to a medication safety advisory the FDA published three weeks ago, the final five survival statistics from DUO revealed what the FDA thinks to be a possible elevated risk of death for Copiktra. By the time of the research, people who took Copiktra had lived a median of 52.3 months, compared to 63.3 months for those who took Arzerra. Serious side effects were mentioned as the cause of the problem with longer-term patient survival during the PI3K meeting in April, as was previously stated.
The impact of the FDA’s PI3K review is extensive. In addition to Copiktra, Gilead Sciences pulled two targets for its PI3K inhibitor Zydelig earlier this year: follicular lymphoma and SLL. This was done because the prerequisites for confirmatory trials were not met.
After the FDA made it plain that it needed to see phase 3 results first, Incyte withdrew a medication application in January for its PI3K inhibitor parsaclisib for relapsed follicular lymphoma, marginal zone lymphoma, and mantle cell lymphoma. Later, when MEI Pharma applied to use the drug zandelisib in partnership with Kyowa Kirin, the FDA made the same demand. Bayer also halted registrations for its Aliqopa treatment for non-Hodgkin’s lymphoma that is indolent.
The FDA had started a broad industry assessment of the expedited approvals given to PD-1/L1 immuno-oncology treatments before the PI3K medications. During that procedure, Merck, BMS, AstraZeneca, and Roche withdrew a number of prescriptions for their medications, including those for triple-negative breast cancer, small cell lung cancer, bladder cancer, and other conditions.