RE: Nothing on socials from any of the board18 Aug 2025 15:31
We really have gotten the best outcome we could have hoped for here with Grok estimating interim analysis at for submission for AA filing at 50-120 patients…
Which would give us the entire FL & R/R population with full approval at the end of the trial…
Phase 2/3 Trial Design:
• The current Phase 2/3 trial includes a dose optimization run-in period comparing 1 mg/kg and 3 mg/kg of bexmarilimab with placebo, in combination with azacitidine, before transitioning to the Phase 3 portion.
• The interim analysis will assess CR + CReq as a co-primary endpoint, which is a surrogate endpoint reasonably likely to predict clinical benefit (e.g., overall survival), supporting accelerated approval.
• Typical Patient Numbers for Interim Analysis:
• For hematologic malignancies like HR-MDS, interim analyses for accelerated approval often involve 50–200 patients in the Phase 2 portion, depending on the rarity of the disease and the strength of the surrogate endpoint.
• For rare diseases or conditions with high unmet need (like HR-MDS, with ~180,000–510,000 global diagnoses and limited options), the FDA may accept data from as few as 50–100 patients if the effect size is large and safety is well-characterized.
• Faron’s prior Phase 1/2 data suggest a robust effect size (e.g., 63–76% ORR vs. 0–20% for existing treatments), which could justify a smaller sample size for interim analysis.
• Best Guess:
• Based on the Phase 2 portion’s focus on dose optimization (1 mg/kg vs. 3 mg/kg vs. placebo) and the precedent set by the BEXMAB trial’s 32 r/r HR-MDS patients, the interim analysis will likely involve 60–120 patients across the dosing arms and placebo.
• Rationale:
• The Phase 2 portion needs enough patients to compare efficacy and safety across two doses and placebo, likely requiring 20–40 patients per arm (including placebo) to achieve statistical significance for CR + CReq.
• The BEXMAB trial’s 32 r/r patients provided sufficient data for FDA Fast Track Designation, suggesting a similar or slightly larger cohort (e.g., 60–90 patients for active arms, plus 20–30 for placebo) could support an interim analysis for accelerated approval.
• The FDA’s Project Frontrunner encourages smaller, efficient trials for unmet needs, and HR-MDS’s poor prognosis (5–6 months mOS in r/r) supports a modest sample size if the response rate remains high (e.g., >50%).
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