BioNTech mRNA癌症疫苗BNT113三期PFS未达标，盘前跌约4.5%，OS终点仍待读出

A phase 2/3 clinical trial of BioNTech’s mRNA cancer immunotherapy BNT113 has missed one of its dual primary endpoints. But with immature overall survival (OS) data offering a path to redemption, the German biotech is continuing to track patients in the metastatic head and neck cancer study.
Hopes for BioNTech’s mRNA cancer immunotherapy pipeline jumped in August, when Merck & Co. and Moderna’s phase 3 data reset expectations for the wider field. But having seen its share price rise 20% on the strength of external data, BioNTech came back to earth with a bump on Tuesday after it failed to replicate its rivals’ success.
BioNTech reported data from the phase 3 part of Ahead-Merit, an open-label trial assessing whether adding BNT113 to Keytruda yields better results than Merck’s checkpoint inhibitor as a monotherapy. The study enrolled patients with HPV16-positive head and neck squamous cell carcinoma (HNSCC).


The Mainz, Germany-based biopharma revealed this morning that progression-free survival (PFS) was statistically no better on the BNT113 regimen than on single-agent Keytruda, causing the study to miss one of its dual primary endpoints. Despite that, the independent data monitoring committee recommended that the trial continue as planned to evaluate OS, the study’s other primary endpoint. The statistical design means an OS hit would establish a positive trial outcome.
On paper, BNT113 could treat HNSCC by triggering immune responses against HPV16 oncoproteins E6 and E7 and by boosting pre-existing T-cell immunity. The mechanism could complement T-cell responses induced by Keytruda. The phase 3 data show BNT113 “is engaging its intended therapeutic mechanism,” BioNTech Chief Medical Officer Özlem Türeci, M.D., said in a statement.
Türeci outlined how the trial could miss on PFS but hit on OS. Immune-mediated antitumor effects can build and deepen over time, the executive said. As that happens, BioNTech could show that BNT113 provides durable benefits to HNSCC patients.

It is plausible that the immune response triggered by BNT113 takes time to fully deepen, BMO Capital Markets analysts said in a note to investors, leaving the door open to OS improvement. Yet the PFS miss made the analysts “significantly” less confident that BNT113 will extend OS.
Precedents exist for cancer immunotherapies improving OS after failing to extend PFS. A phase 3 clinical trial of Keytruda in HNSCC missed its PFS endpoint but went on to show the checkpoint inhibitor improved OS. Keytruda retained its OS advantage across five years of follow-up. Yet while such examples show BNT113 still has a shot, many trials that miss PFS endpoints later flunk OS assessments.
BioNTech’s stock dropped 5% to $91.32 in premarket trading Tuesday from a Monday closing price of $95.84, while Moderna’s share price also dipped 3%.
Both biotechs are developing mRNA cancer immunotherapies, although BNT113 differs from Moderna’s high-profile intismeran autogene as it encodes a fixed set of antigens. In contrast, intismeran autogene contains antigens that are tailored to the mutations found in each patient’s tumor. 
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