100% responder rate in pivotal trial sets up a single-arm BLA filing — can a novel milestone endpoint survive FDA scrutiny?

Taysha Gene Therapies is a clinical-stage gene therapy company developing TSHA-102 to treat Rett syndrome, a rare neurological disorder in girls, which is not yet approved.

TSHA-102, a gene therapy restoring MECP2 function in girls with Rett syndrome, achieved a 100% response rate across 12 patients at 12 months with no treatment-related SAEs or DLTs, earning Breakthrough Therapy Designation. The thesis turns on whether the 6-month interim analysis replicates that signal and FDA accepts the single-arm, milestone-gain endpoint as sufficient for approval. The primary risk is that a novel, patient-as-own-control primary endpoint in a small single-arm trial lacks the regulatory precedent to clear a BLA without additional scrutiny.