RARE Daily

Astellas Updates Preliminary Data from Study of Experimental Pompe Disease Gene Therapy

February 23, 2023

Rare Daily Staff

Astellas Pharma updated preliminary safety and efficacy data from its ongoing FORTIS phase 1/2 clinical trial evaluating the safety, tolerability and exploratory efficacy of investigational AT845 in adults with late-onset Pompe disease.

The data will be presented during a platform presentation at the 19th Annual WORLDSymposium in Orlando, Florida.

Pompe disease is a rare, severe, autosomal recessive metabolic disease characterized by progressive neuromuscular degeneration. The disease is caused by mutations in the acid alpha-glucosidase (GAA) gene that prevent the production and function of a protein called acid alpha-glucosidase (GAA). GAA is responsible for metabolizing glycogen, and dysfunction or absence of this protein results in the accumulation of glycogen in tissues, primarily in the skeletal and cardiac muscles, where it causes damage to tissue structure and function. Currently, the only approved treatment for Pompe is enzyme replacement therapy (ERT), which is a chronic treatment delivered in bi-weekly infusions and relies solely on tissue uptake of GAA from plasma.

AT845 is an investigational adeno-associated virus (AAV) gene replacement therapy designed to deliver a functional human GAA gene directly in muscle cells in adults with Late-Onset Pompe disease (LOPD).

FORTIS is an ongoing multicenter, open-label, ascending dose phase 1/2 first-in-human clinical trial to determine the safety, tolerability and exploratory efficacy of AT845 in adults with LOPD. As of the September 15th, 2022, data cut-off, four participants received a one-time intravenous infusion of AT845, with two dosed at the 3×1013 vg/kg dose level and two dosed at the 6×1013 vg/kg dose level, with up to 78 weeks of safety follow-up in the clinical trial.

Three of the four participants have discontinued ERT following administration of AT845, and their measured functional outcomes have been stable while off ERT for 19, 44, and 51 weeks, respectively. The ongoing evaluation of the dosed participants, including those who discontinued ERT, showed continued stability of disease functional endpoints, including forced vital capacity and the 6-minute walk test. Patient-reported outcomes for fatigue and daily activities (Pompe-specific) also appeared stable.

Each participant’s infusion of AT845 was generally well-tolerated, and most treatment-emergent adverse effects were mild (grade 1) and considered to be unrelated to study treatment. A possible infusion-related reaction occurred in one participant and resolved with oral diphenhydramine and acetaminophen. Three participants developed transient transaminitis and deemed possibly related to AT845. In all cases, the event resolved with modifications to immune suppression. A grade 2 peripheral sensory polyneuropathy event was reported in one participant in the 6×1013 vg/kg cohort, which led to a U.S. Food and Drug Administration clinical hold in June 2022. The FDA lifted this clinical hold in January 2023.

“These data, along with our recent announcement of the clinical hold lift of the FORTIS clinical trial, are very positive developments for the program,” said Ha Tran, executive medical director for Astellas. “The preliminary data presented are encouraging. We look forward to continuing the FORTIS clinical trial as we advance towards our goal of developing innovative gene therapies and bringing new potential treatments to patients with high unmet need.”

Photo: Ha Tran, executive medical director for Astellas

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