While BNT113 failed to improve progression-free survival in patients with a type of head and neck cancer during a Phase 3 trial, BioNTech is holding out hope for an overall survival win—but analysts say that outcome is now “less likely.”
BioNTech’s recent run of bad luck with its mRNA cancer immunotherapy pipeline continued Tuesday, as the company reported that one candidate, BNT113, failed to significantly improve progression-free survival in patients with a type of head and neck cancer in a closely watched Phase 3 trial.
“Results add to a growing list of recent mRNA cancer vaccine setbacks including two discontinuations for autogene cevumeran in bladder cancer and colorectal cancer,” BMO Capital Markets wrote in a note to investors Tuesday morning.
BioNTech halted a Phase 2 trial of autogene cevumeran in colorectal cancer in August due to futility following a recommendation by an independent data safety monitoring board. This followed the discontinuation earlier this year of a Phase 2 trial for the asset in bladder cancer “due to the rapidly emerging treatment landscape and shifting standard of care,” the company said.
The most recent miss, announced on Tuesday, comes from the Phase 2/3 AHEAD-MERIT trial, which is testing the mRNA immunotherapy in combination with Merck’s Keytruda vs. Keytruda alone for the first-line treatment of metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC). The trial, which has enrolled 358 patients, has dual primary endpoints: progression-free survival (PFS) and overall survival (OS).
BioNTech shares wobbled upon market open on Tuesday, falling 5% to $90.88.
Despite the PFS miss, the German biotech isn’t giving up hope on the trial just yet, suggesting that a positive readout on OS could still render the trial a success. The trial will therefore continue on to evaluate OS, “completing the assessment with the potential of this treatment approach to help patients live longer,” BioNTech said in its press release.
“Under the trial’s pre-specified statistical design, a statistically significant improvement in overall survival would establish a positive trial outcome, even if the progression-free survival dual primary endpoint was not met,” the company clarified in its announcement. This is in line with the recommendation of an independent data monitoring committee, BioNTech added.
BMO agreed that overall survival could still be achieved despite the PFS miss but said so with “significantly reduced confidence.” The firm noted, “While improvement in overall survival is still possible, we view such a scenario as less likely given today’s PFS miss.”
Around one-third of HNSCC cases are associated with HPV infection, with the majority linked to HPV16, BioNTech said in its release, adding that there are currently no HPV-targeted treatments approved. BioNTech is hoping to change that with BNT113, which encodes a fixed set of antigens to specifically target two HPV16-derived antigens that are frequently expressed on HPV16+ tumor cells.
BMO noted that as an mRNA vaccine, BNT113 is designed to induce an immune response against those target proteins. “This response may take longer to fully deepen, supporting the possibility that AHEAD-MERIT misses on PFS improvement, but an overall survival benefit can still materialize over time.”
BNT113 and autogene cevumeran are part of BioNTech’s personalized cancer immunotherapy pipeline that also includes BNT116, which is currently in Phase 2 development for metastatic non-small cell lung cancer (NSCLC) and Phase 1 for NSCLC.
Autogene cevumeran scored a win in a small Phase 1 trial in April. The study showed that nearly 90% of participants with pancreatic cancer whose immune systems responded to the immunotherapy plus Roche’s checkpoint inhibitor Tecentriq and chemotherapy were still alive up to six years after receiving the last treatment. The combo is currently in a Phase 2 study, which is expected to be complete in January 2031.
