OS Therapies seeks FDA alignment on survival endpoint for osteosarcoma gene therapy

OS Therapies, Inc. (NYSE American: OSTX) has requested a Type B meeting with the US FDA to resolve a central unresolved question in its Biologics License Application (BLA) for OST-HER2 (daznelimgene lisbac) in pulmonary metastatic osteosarcoma: whether 3-year overall survival, supported by pharmacodynamic biomarker data, constitutes an approvable efficacy endpoint under the Accelerated Approval Program. The meeting is expected to determine whether the FDA accepts the company’s proposed regulatory strategy for Accelerated Approval, a decision that will dictate whether the BLA remains on track and whether OS Therapies can secure a Rare Pediatric Disease Priority Review Voucher before the program expires.

The core regulatory obstacle is endpoint alignment. Following a September 2025 End of Phase II meeting, the FDA indicated that acceptable comparator arms and statistical analysis methods had not been fully agreed upon. The company has since submitted pharmacodynamic response biomarker data to the FDA’s Biomarkers, EndpointS, and other Tools (BEST) program for evaluation as a surrogate clinical efficacy measure. The Type B meeting is intended to confirm whether the combination of 3-year overall survival data and the immune activation biomarker signature — which the company reported as correlating with clinical outcomes in its Phase IIb trial — will satisfy the agency’s standard for adequate evidence of effectiveness under Accelerated Approval.

The FDA has not yet granted rolling review, Regenerative Medicine Advanced Therapy (RMAT) designation, or Breakthrough Therapy Designation (BTD) for OST-HER2. OS Therapies said it intends to seek resolution on all three outstanding requests at the same Type B meeting. The agency had previously confirmed that OST-HER2 meets the biological definition of a gene-edited product qualifying for RMAT consideration, but has not issued a formal designation.

A parallel regulatory dimension involves the comparator arm. Following the September 2025 End of Phase 2 meeting, the FDA indicated that suitable comparators for the single-arm Phase IIb trial had not been finalized. The company has assembled the OST-400 natural history database — a retrospective longitudinal study of recurrent osteosarcoma in children and young adults — and said that recruitment has now reached a level sufficient to propose OST-400 as a synthetic control comparator arm. This is in addition to pooled historical control data previously shared with the agency. The Type B meeting agenda includes FDA review of OST-400’s potential role as a second supportive comparator, alongside discussion of statistical analysis methods consistent with the FDA’s 2023 Rare Diseases guidance.

The regulatory situation differs across jurisdictions. The UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have both aligned on 3-year overall survival as the proposed approvable endpoint for conditional marketing authorizations, and the EMA has initiated rolling review of the conditional Marketing Authorisation Application (MAA). The FDA has not yet reached the same alignment, making the Type B meeting the critical near-term regulatory gate for the US pathway. FDA and EMA have begun joint coordination on the OST-HER2 dossier, which OS Therapies said it hopes will facilitate convergence.

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OST-HER2 is a gene-edited, Listeria monocytogenes-based cancer immunotherapy targeting HER2. It is designed to infect HER2-expressing tumor cells and trigger an innate and adaptive immune response directed against HER2-positive osteosarcoma. The drug targets two mutated extracellular epitopes and one mutated intracellular epitope of the HER2 oncogene, requiring only one of the three to be present in a tumor or micro-metastasis to elicit the desired immune response. Osteosarcoma is a rare bone cancer primarily affecting adolescents and young adults; pulmonary metastatic osteosarcoma carries poor long-term prognosis and has seen no new approved therapies in more than 40 years. OST-HER2 has received Orphan Drug Designation, Fast Track Designation, and Rare Pediatric Disease Designation (RPDD) from the FDA.

The Phase IIb trial of OST-HER2 in 40 patients reported statistically significant benefit in the 12-month event-free survival primary endpoint (35% vs. 20% historical control, p = 0.0197) and 2-year overall survival (75% vs. 40%, p < 0.0001). The company has also reported 2.5-year overall survival data at the 2026 ASCO Annual Meeting, which it intends to present to the FDA at the Type B meeting as part of the endpoint alignment discussion.

OS Therapies said it expects the Type B meeting to occur in the near term, while three-year overall survival data is anticipated in early fall 2026. Completion of the BLA submission, including the clinical module, is expected to follow the meeting. The company said it anticipates regulatory decisions from the FDA, EMA, and MHRA in the second half of 2026, with a confirmatory Phase III trial expected to commence in Australia in Q3 2026 — a prerequisite for BLA grant under the Accelerated Approval Program.


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