Monoclonal antibody for FSHD improves muscle strength with no serious adverse events

Avidity Biosciences Inc. has announced positive data from the phase 1/2 FORTITUDE clinical trial of a proprietary monoclonal antibody that binds to the transferrin receptor 1 conjugated with a siRNA targeting DUX4 mRNA.

According to a company release, AOC 1020 (delpacibart braxlosiran) demonstrated consistent reductions of greater than 50% in DUX4 regulated genes, functional improvement and favorable safety and tolerability in people living with facioscapulohumeral muscular dystrophy (FSHD).

Avidity additionally stated that AOC 1020’s approved international proprietary name will be abbreviated as del-brax.

The randomized, double-blind, placebo-controlled FORTITUDE trial examined safety and tolerability over 4 months for 39 participants across two dose levels (2 mg/kg and 4 mg/kg).

For the 4-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.

Initial data showed treatment resulted in:

• Reductions greater than 20% in DUX4 regulated genes and mean reductions of 25% or greater in novel circulating biomarker and creatine kinase.

• Functional improvements including increased strength in upper and lower limb muscles, as well as muscle function measured by reachable workspace compared with placebo and the ReSolve natural history study.

• Trends of improvement in patient- and clinician-reported outcomes, adverse events being mild or moderate, with no serious adverse events and no discontinuations.

“We are now focused on accelerating our registrational plans as we understand the urgency to develop a treatment for people living with [facioscapulohumeral muscular dystrophy] who have no treatment options,” Avidity President and CEO Sarah Boyce said in the release. “By directly targeting the root cause, we believe that del-brax has the potential to be a first-in-class, best-in-class therapy.”