RARE Daily

FDA Grants Orphan Drug and Rare Pediatric Designations for Dyne’s Treatment for Duchenne Muscular Dystrophy

March 23, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has granted orphan drug and rare pediatric disease designations to Dyne Therapeutics’ DYNE-251, an investigational therapeutic for Duchenne muscular dystrophy mutations amenable to exon 51 skipping.

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 U.S. 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.

“These regulatory designations highlight the urgent and critical need for new and better therapeutic options for people living with this fatal disease,” said Wildon Farwell, chief medical officer of Dyne.

DYNE-251 is being evaluated in the Phase 1/2 global DELIVER clinical trial for people living with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping. The DELIVER clinical trial consists 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 initial data from the MAD placebo-controlled portion of the DELIVER trial on safety, tolerability, and dystrophin in the second half of 2023.

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. DYNE-251 demonstrated a favorable safety profile and achieved robust exon skipping in non-human primates, especially in the heart and diaphragm, muscles in people living with DMD that weaken over time leading to mortality. DYNE-251 was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of DMD in people who are amenable to exon 51 skipping.

Orphan drug designation is granted by the FDA to drugs or biological products intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the United States.

The Rare Pediatric Disease designation program is offered by the FDA to encourage the development of new drugs for rare pediatric diseases (diseases affecting children 18 years of age and younger and fewer than 200,000 people in the United States). Under the RPD program, a sponsor who receives approval for a drug or biologic for a rare pediatric disease for which the RPD designation has been granted, may qualify for a priority review voucher (PRV) at the time of market approval. Holders of a PRV can redeem the voucher to obtain priority review, which shortens review from 10-months to 6-months, for any subsequent marketing application, or they can sell or transfer it to other developers. Recently, Bluebird Bio sold two PRVs, one for $95 million and one for $102 million.

Photo: Wildon Farwell, chief medical officer of Dyne

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