The 5 Most Painful Clinical Trial Failures of 2025

Contineum Therapeutics' PIPE-307 failed mid-stage trial for relapsing-remitting MS, missing primary vision test endpoint and secondary measures despite acceptable safety1.

Capsida Biotherapeutics' gene therapy for STXBP1-related disorders resulted in a child's death from cerebral edema just days after dosing, raising safety concerns for brain-targeted viral vectors4.

Sarepta's exon skippers Vyondys 53 and Amondys 45 for Duchenne muscular dystrophy failed confirmatory ESSENCE trial's primary endpoint of stair-climbing ability at 96 weeks, despite initial approvals on biomarker data5.

Biogen's Qalsody for amyotrophic lateral sclerosis (ALS) failed to show efficacy in pivotal or confirmatory trials, highlighting issues with biomarker-based approvals5.

MacroGenics' Margenza for breast cancer failed pivotal trials, contributing to debates on handling FDA-approved drugs that miss efficacy endpoints post-approval5.

Sources:

1. https://www.biopharmadive.com/news/contineum-ms-trial-failure-johnson-johnson-neuroscience/806127/

4. https://www.statnews.com/2025/12/15/gene-therapy-capsida-biotherapeutics-clinical-trial-death-ramifications/

5. https://www.biospace.com/fda/fdas-conundrum-what-to-do-with-approved-drugs-that-fail-pivotal-or-confirmatory-trials