Avidity Biosciences Receives FDA Orphan Drug Designation for for Treatment of Duchenne Muscular Dystrophy in People With Mutations Amenable to Exon 44 Skipping

Avidity Biosciences, Inc. recently announced the US FDA has granted Orphan Drug designation to AOC 1044, the company’s investigational therapy in development for the treatment of Duchenne muscular dystrophy (DMD) in people with mutations amenable to exon 44 skipping (DMD44). DMD is a rare genetic condition that is characterized by progressive muscle damage and weakness due to the loss of dystrophin protein that typically starts at a very young age. Currently, there are no therapies approved targeting exon 44.

AOC 1044 is being assessed in the Phase 1/2 EXPLORE44 clinical trial for people living with DMD44 and is the first of multiple AOCs in development at Avidity for the treatment of DMD. Avidity plans to share results from the healthy volunteer portion of the EXPLORE44 trial in the fourth quarter of 2023 and is now enrolling participants living with DMD44 into the study. In April 2023, AOC 1044 received FDA Fast Track designation for the treatment of DMD44.

“We are pleased that the FDA has granted both Orphan Drug and Fast Track designation to AOC 1044, highlighting the importance of advancing new treatments for people living with DMD,” said Steve Hughes, MD, Chief Medical Officer at Avidity. “There are currently no treatment options that target the underlying cause of DMD44. AOC 1044 is designed to specifically skip exon 44 of the dystrophin gene to enable the production of functional dystrophin protein. We look forward to advancing AOC 1044 in clinical development and bringing this very important treatment to patients as quickly and safely as possible.”

Avidity’s proprietary AOCs are designed to combine the specificity of monoclonal antibodies (mAbs) with the precision of oligonucleotide therapies to target the root causes of diseases previously untreatable with RNA therapeutics. In the case of DMD, the disease is caused by a genetic mutation that prevents the body from producing the dystrophin protein, which protects muscle cells from injury during contraction. The lack of functional dystrophin leads to stress and tears of muscle cell membranes, resulting in muscle cell death, inflammation, and progressive loss of muscle function. AOC 1044 is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue. The PMOs circumvent the mutation by causing exon 44 of the dystrophin gene to be skipped, which enables production of functional dystrophin protein.

The FDA’s Office of Orphan Products Development grants orphan status to support the development of medicines for rare disorders that affect fewer than 200,000 people in the US Orphan Drug designation provides certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

The EXPLORE44 trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial to evaluate AOC 1044 in healthy volunteers and participants with DMD mutations amenable to exon 44 skipping (DMD44). EXPLORE44 will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of AOC 1044 administered intravenously. EXPLORE44 is expected to enroll approximately 40 healthy volunteers and 24 participants with DMD44, ages seven to 27 years old. The EXPLORE44 trial will assess exon skipping and dystrophin protein levels in participants with DMD44. Participants with DMD44 will have the option to enroll into an extension study.

Duchenne muscular dystrophy (DMD) causes a lack of functional dystrophin that leads to stress and tears of muscle cell membranes, resulting in muscle cell death and the progressive loss of muscle function. The dystrophin protein maintains the integrity of muscle fibers and acts as a shock absorber through its role as the foundation of a group of proteins that connects the inner and outer elements of muscle cells. People living with DMD suffer from progressive muscle weakness that typically starts at a very young age. Over time, people with Duchenne will develop problems walking and breathing, and eventually, the heart and respiratory muscles will stop working. Those living with the condition often require special aid and assistance throughout their lives and have significantly shortened life expectancy. While there are treatments approved to treat people with DMD, there remains a very high unmet need. DMD is a monogenic, X-linked, recessive disease that primarily affects males, with one in 3,500 to 5,000 boys born worldwide having Duchenne.

AOC 1044 is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene to enable dystrophin production in people living with Duchenne muscular dystrophy with mutations amenable to exon 44 skipping (DMD44). DMD is characterized by progressive muscle degeneration and weakness due to alterations of a protein called dystrophin that protects muscle cells from injury during contraction. AOC 1044 consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a PMO targeting exon 44. In a preclinical model of DMD, a murine active AOC produced durable exon skipping and functional dystrophin protein in skeletal muscle and heart tissue following a single intravenous dose. AOC 1044 is currently in Phase 1/2 development as part of the EXPLORE44 trial for the treatment of DMD mutations amenable to exon 44 skipping.

Avidity Biosciences, Inc.’s mission is to profoundly improve people’s lives by delivering a new class of RNA therapeutics – Antibody Oligonucleotide Conjugates (AOCs). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through internal discovery efforts and key partnerships. Avidity is headquartered in San Diego, CA. For more information, visit www.aviditybiosciences.com.