The FDA has put all studies of Oncopeptides’ melflufen on partial hold after a blinded reassessment of phase 3 data found large differences in overall survival in pre-specified subgroups.
Oncopeptides presented top-line data from a phase 3 trial comparing its peptide-drug conjugate to Bristol Myers Squibb’s Pomalyst in multiple myeloma in May. The analysis by the independent review committee found melflufen was no better than Pomalyst in terms of progression-free survival (PFS), but the investigator assessment showed the Oncopeptides drug was superior.
While preparing the clinical study report and regulatory documents, Oncopeptides discovered that the committee lacked access to all the information in the clinical database. The discovery led to the blinded reassessment of the full 495-patient database by the independent review committee.
After reassessing data from 29 patients in the OCEAN trial, the committee found PFS in the melflufen arm was better than the Pomalyst cohort, causing the study to hit its primary endpoint with a p-value of 0.0311. However, the analysis also raised a red flag.
Melflufen did not beat Pomalyst on overall survival, a key secondary endpoint of the trial. The overall survival (OS) hazard ratio (HR) was 1.104 in favor of Pomalyst. Having analyzed the OS data, Oncopeptides believes its survival results are “primarily explained by substantial HR differences between pre-specified subgroups in both directions.” In light of those differences, the FDA has put a partial clinical hold on all studies of melflufen.
Exactly what that means for melflufen, which is branded Pepaxto, remains unclear. Jefferies analysts outlined what is riding on the assessment of the risks and benefits of melflufen in a note to investors.
“A c.10% higher risk of death vs Pomalyst is concerning, even if likely attributed to subgroups. We anticipate OCEAN data to be critical determinants of Pepaxto’s 3rd+ line peak penetration, which, given the longer treatment duration vs salvage therapy, is a key value driver,” the analysts wrote.
Oncopeptides said it will work with the FDA to perform the analyses needed to understand the risks and benefits of melflufen and identify the patients likely to benefit from earlier treatment with the drug.
Shares in Oncopeptides fell 23% after the release of the update.