The US Food and Drug Administration (FDA) lifted the clinical hold placed on the investigational drug DYNE-251 for the treatment of Duchenne muscular dystrophy (DMD), according to a press release from Dyne Therapeutics, the developers of the drug. The company will now start dosing participants in a phase 1/2 clinical trial testing the drug candidate.

“The clearance of our first [Investigational New Drug] is an important achievement for Dyne, and we appreciate the partnership with the FDA throughout this process,” Joshua Brumm, president and chief executive officer of Dyne said in a press release.

“Our team has worked extensively with key opinion leaders, patient advocacy groups and individuals living with DMD to thoughtfully design and execute our global multiple-ascending dose Phase 1/2 clinical trial of DYNE-251.”


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DYNE-251 is an exon-skipping drug that consists of a phosphorodiamidate morpholino oligomer conjugated to a fragment antibody (Fab). The Fab binds to the transferrin receptor 1, which is highly expressed in muscles. The aim is to deliver the morpholino specifically to the muscles so that a truncated but still functional dystrophin protein can be made there.

Read more about exon skipping for DMD

In the mdx mouse model, DYNE-251 treatment led to robust and durable exon skipping and dystrophin expression in skeletal and heart muscle and led to reduced muscle damage and increased muscle function. Experiments in nonhuman primates have shown that DYNE-251 has a favorable safety profile and “achieved impressive exon skipping.”

The phase 1/2 clinical trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of DYNE-251 as well as its effect on dystrophin expression and muscle function. It aims to recruit 30 to 50 patients with DMD, aged 4 to 16 years with a mutation amenable to exon 51 skipping. The randomized, placebo-controlled, multiple ascending dose trial will also have a long-term extension phase. Additional information about the design and timing of the trial will be made available by the company once dosing starts.

Reference

Dyne Therapeutics announces FDA clearance of IND application for DYNE-251 for the treatment of Duchenne muscular dystrophy. News release. Dyne Therapeutics; July 5, 2022.