Avidity Biosciences, Inc. announced positive initial AOC 1020 data from the Phase 1/2 FORTITUDE? trial demonstrating unprecedented and consistent reductions of greater than 50% in DUX4 regulated genes, trends of functional improvement, and favorable safety and tolerability in people living with facioscapulohumeral muscular dystrophy (FSHD). Avidity plans to accelerate initiation of registrational cohorts in the FORTITUDE?

study. Avidity also announced delpacibart braxlosiran as the approved international nonproprietary name of AOC 1020, abbreviated as del-brax. Del-brax is the first investigational therapy designed to treat the underlying cause of FSHD, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4.

FSHD is a rare, hereditary disorder marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. Currently, there are no approved therapies for the treatment of FSHD. The AOC 1020 initial data will be highlighted in an oral presentation at the 31st Annual FSHD Society International Research Congress, being held June 13-14, 2024, in Denver, Colorado.

The initial assessment from the randomized, double-blind, placebo-controlled Phase 1/2 FORTITUDE trial of del-brax provides a four-month look at the safety and tolerability for all 39 participants across two dose levels (2 mg/kg and 4 mg/kg). For the four-month assessment in the 2 mg/kg cohort, participants received a single-dose of 1 mg/kg del-brax followed by two doses of 2 mg/kg del-brax (siRNA dose), or placebo. Data on DUX4 regulated genes, circulating biomarkers and muscle strength and function were assessed from 12 participants in the 2 mg/kg cohort.

In the Phase 1/2 FORTITUDE study, del-brax demonstrated: Greater than 50% mean reductions in DUX4 regulated genes across multiple panels for DUX4 regulated gene expression in muscle. All participants treated with del-brax showed reductions greater than 20% in DUX4 regulated genes. Mean reductions of 25% or greater in novel circulating biomarker and creatine kinase.

Trends of functional improvements including increased strength in upper and lower limb muscles, and muscle function as measured by reachable workspace (RWS) compared to placebo and the ReSolve natural history study. Trends of improvement in patient and clinician reported outcomes. Favorable safety and tolerability with all adverse events (AEs) mild or moderate, no serious adverse events and no discontinuations.