Recently released data from a phase 1/2 clinical trial show that combination therapy led to significant dystrophin expression and functional improvement in patients with Duchenne muscular dystrophy amenable to exon 51 skipping, according to researchers.
Duchenne muscular dystrophy is a fatal, X-linked neuromuscular disease that results in progressive loss of muscle function. It is caused by alterations in the dystrophin gene (DMD) that reduce dystrophin protein production to less than 3% of the normal level.
Healio reports that DYNE-251 is a phosphorodiamidate morpholino oligomer conjugated to a fragment antibody that binds to the transferrin receptor 1, said manufacturer Dyne Therapeutics. Developed to positively target muscle tissue and promote exon skipping in the nucleus, the treatment’s mechanism of action permits muscle cells to create dystrophin proteins that either reverse or halt disease progression.
The novel therapeutic is currently being examined in the DELIVER clinical trial, a global, randomised, placebo-controlled study that includes children and adolescents aged four to 16 years with the rare neuromuscular condition.
The company said that those given 20mg/kg of DYNE-251 every four weeks recorded a mean absolute dystrophin expression of 3.71% of normal, more than 10-fold higher than the 0.3% reported in a clinical trial of eteplirsen, the standard treatment for patients with Duchenne.
Additionally, study data showed meaningful improvements in multiple functional endpoints in groups given 10 mg/kg and 20 mg/kg every four weeks, including on North Star Ambulatory Assessment, Stride Velocity 95th Centile, 10m Walk/Run Time as well as Time to Rise from Floor metrics. Researchers also found those in the 10mg/kg cohort logged consistent improvement across all relevant metrics from six months to 12 months.
Further, Dyne reported that among 54 participants, the drug demonstrated a favourable safety profile with most treatment emergent adverse events being mild or moderate.
“We believe these data reinforce the opportunity to transform the treatment paradigm for individuals living with Duchenne,” said Wildon Farwell, MD, MPH, chief medical officer of Dyne. “We are moving quickly to initiate registrational cohorts in DELIVER, and plan to provide an update on registration by the end of this year.”
Healio article – Novel Duchenne therapy shows promise for halting disease progression (Open access)
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