AOC 1020, an investigational treatment by Avidity Biosciences that’s now called delpacibart braxlosiran, or del-brax, helped adults with facioscapulohumeral muscular dystrophy (FSHD) grow stronger muscles and extend their arms farther than they could four months earlier. These are early data from FORTITUDE (NCT05747924), a three-part Phase 1/2 clinical trial that’s testing how safe del-brax is for treating FSHD and how well it works over a placebo on measures of muscle strength and function, among others. Avidity plans to move quickly to gain enough data to seek del-brax’s approval.
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. 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.
A so-called antibody-oligonucleotide conjugate, del-brax is made up of an antibody that binds to the transferrin receptor 1 in muscles cells and is attached to a small interfering RNA, or siRNA, that reduces DUX4 mRNA, a molecule that carries genetic instructions from DNA.
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
- 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
https://musculardystrophynews.com/news/ ... treatment/