RARE Daily

FDA Grants Fast Track Designation to Dyne’s Treatment for Duchenne Muscular Dystrophy

October 31, 2022

The U.S. Food and Drug Administration has granted Fast Track designation for Dyne Therapeutics’ DYNE-251 for the treatment of Duchenne muscular dystrophy with mutations amenable to exon 51 skipping.

Photo: Wildon Farwell, chief medical officer of Dyne

“Every day is critical for patients and their families, and we are pleased that the FDA granted Fast Track designation as this provides an opportunity to expedite the development of DYNE-251,” said Wildon Farwell, chief medical officer of Dyne. “Duchenne is a fatal disease and available therapies offer limited benefit. We are focused on driving toward meaningful clinical data in our DELIVER trial anticipated in the second half of 2023 and continuing to work closely with the DMD community and the FDA to advance a potentially transformative therapy.”

The FDA grants Fast Track designation to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need, with the ultimate goal of getting important new drugs to patients earlier. A drug that receives Fast Track designation may be eligible for more frequent meetings and communications with the FDA and rolling review of any application for marketing approval, which may lead to earlier drug approval and access by patients. A drug receiving Fast Track designation also may be eligible for Accelerated Approval and Priority Review if relevant criteria are met.

Duchenne muscular dystrophy (DMD) is a rare disease caused by mutations in the gene that encodes for dystrophin, a protein critical for the normal function of muscle cells. These mutations, the majority of which are deletions, result in the lack of dystrophin protein and progressive loss of muscle function. DMD occurs primarily in males and affects an estimated 12,000 to 15,000 individuals in the United States and 25,000 in Europe. Loss of strength and function typically first appears in pre-school age boys and worsens as they age. As the disease progresses, the severity of damage to skeletal and cardiac muscle often results in patients experiencing total loss of ambulation by their early teenage years and includes worsening cardiac and respiratory symptoms and loss of upper body function by the later teens. There is no cure for DMD and currently approved therapies provide limited benefit.

DYNE-251 is Dyne’s product candidate being developed for people living with DMD who are amenable to exon 51 skipping. DYNE-251 consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to a fragment antibody (Fab) that binds to the transferrin receptor 1 (TfR1) which is highly expressed on muscle. It is designed to enable targeted muscle tissue delivery and promote exon skipping in the nucleus, allowing muscle cells to create a truncated, functional dystrophin protein, with the goal of stopping or reversing disease progression.

In preclinical studies with Dyne’s FORCE platform, robust and durable exon skipping and dystrophin expression were observed in the mdx mouse model in skeletal and cardiac muscle as well as reduced muscle damage and increased muscle function. In non-human primates, DYNE-251 demonstrated a favorable safety profile and achieved impressive exon skipping, especially in the heart and diaphragm, muscles in people living with DMD that weaken over time leading to mortality.

DYNE-251 is being evaluated in the phase 1/2 DELIVER global clinical trial consisting of a 24-week multiple ascending dose (MAD) randomized placebo-controlled period, a 24-week open-label extension and a 96-week long-term extension. The trial, which is designed to be registrational, is expected to enroll approximately 46 ambulant and non-ambulant males with DMD who are ages 4 to 16 and have mutations amenable to exon 51 skipping therapy. The primary endpoints are safety, tolerability and change from baseline in dystrophin levels as measured by Western blot. Secondary endpoints include measures of muscle function, exon skipping and pharmacokinetics. Dyne anticipates reporting data from the MAD placebo-controlled portion of the DELIVER trial on safety, tolerability, and dystrophin in the second half of 2023.

Author: Rare Daily Staff

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