Aug 05, 2026 —
Eli Lilly has discontinued a Phase 1/2 trial evaluating LY3884961, its investigational AAV-based GBA1 gene therapy, in Gaucher disease type 1, or GD1.
The program originated from Lilly’s 2020 acquisition of Prevail Therapeutics, a deal valued at approximately $1 billion. Prevail’s two lead AAV gene therapy programs included LY3884961 for GBA1-associated diseases and LY3884963 for frontotemporal dementia. Lilly previously removed LY3884963 from its pipeline in February.
Lilly said the AAV-based GBA1 gene therapy program for Gaucher disease type 1 did not meet the company’s internal bar for success and has been removed from the pipeline. The company also stated that no safety signal was observed.
LY3884961 was being evaluated in a Phase 1/2 study enrolling adults with peripheral manifestations of Gaucher disease type 1. The trial was designed to assess the safety and tolerability of up to three dose levels of the investigational AAV gene therapy.
Gaucher disease type 1 is an inherited lysosomal storage disorder caused by mutations in GBA1, which lead to deficient enzyme activity. AAV gene therapy approaches aim to address the disease at its genetic source by delivering a functional GBA1 gene.
LY3884961 has faced several setbacks since the Prevail acquisition. In 2022, Lilly reported a financial charge primarily related to changes in the estimated launch timing for the gene therapy. In 2024, the company ended development of the asset in Gaucher disease type 2, or GD2.
Although Lilly has discontinued LY3884961 in GD1 and GD2, the company said it will continue evaluating the AAV-based GBA1 gene therapy program in Parkinson’s disease through the PROPEL trial.
The discontinuation narrows Lilly’s AAV gene therapy pipeline. In addition to the Parkinson’s program, Lilly is advancing Phase 1/2 gene therapy trials for otoferlin gene-mediated hearing loss and vestibular schwannoma, both acquired through its 2022 purchase of Akouos.
Lilly’s exit from GD1 removes a major pharmaceutical company from the Gaucher AAV gene therapy field. Other companies remain active, including Spur Therapeutics, which is running a Phase 3 trial of a GBA1 gene therapy in GD1, as well as Lingyi Biotech and Sanofi-backed research programs.
The update highlights the continued challenges of translating AAV gene therapy programs for lysosomal storage disorders, where safety, biodistribution, durability, dose selection, and clinical benefit must align to support further development.
