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uniQure's one-time gene therapy for a rare form of ALS showed early biomarker promise but hit a critical safety wall. Final results from the EPISOD1 trial revealed a dose-limiting nerve toxicity in the mid-dose group, prompting the company to halt development. Five patients remain under long-term safety monitoring.
uniQure has presented final results from its now-discontinued EPISOD1 trial of AMT-162, a one-time gene therapy targeting SOD1-associated ALS (SOD1-ALS) — a rare genetic subtype accounting for roughly 2% of all ALS cases, or fewer than 500 patients in the US. The therapy used an AAVrh10 viral vector to deliver an engineered microRNA designed to silence the mutant SOD1 gene via intrathecal injection.
The Phase 1/2 trial enrolled just 5 participants — 3 in a low-dose cohort and 2 in a mid-dose cohort. While early biomarker signals were encouraging, a Grade 3 serious adverse event of sensory-predominant neuropathy emerged in the mid-dose group, deemed a dose-limiting toxicity. That finding, combined with Grade 2 sensory symptoms in one low-dose patient, tipped the benefit-risk balance unfavorably, leading uniQure to discontinue the program.
By the Numbers:
Why it matters: While AMT-162 won't move forward, the field isn't standing still. Tofersen (Qalsody) already holds FDA accelerated approval for SOD1-ALS, and Avrion Therapeutics is advancing a next-generation AAV9-based candidate (AVR-001) toward a first-in-human trial expected in 2028. The EPISOD1 results add important safety learnings for the broader gene therapy community targeting ALS.
