Avidity Reports Positive Data in DM1 Study

Rare Daily Staff

Avidity Biosciences reported new positive data demonstrating its experimental therapy AOC 1001 led to improvement in multiple additional functional endpoints and favorable long-term safety and tolerability in people living with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is an underrecognized, progressive and often fatal disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease is highly variable with respect to severity, presentation, and age of onset, however all forms of DM1 are associated with high levels of disease burden and may cause premature mortality. DM1 primarily affects skeletal and cardiac muscle, however patients can suffer from a constellation of manifestations including myotonia and muscle weakness, respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. Currently, there are no approved treatments for people living with DM1.

AOC 1001, Avidity’s lead product candidate utilizing its AOC platform, is designed to address the root cause of DM1 by reducing levels of a disease-related mRNA called DMPK. AOC 1001 consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA. In preclinical studies, AOC 1001 successfully delivered siRNAs to muscle cells, resulting in durable, dose-dependent reductions of DMPK RNA across a broad range of muscles including skeletal, cardiac, and smooth muscles. AOC 1001 is currently in phase 1/2 development with the completed MARINA trial and the ongoing MARINA-OLE trial in adults with DM1.

The U.S. Food and Drug Administration and European Medicines Agency have granted Orphan Designation for AOC 1001 and the FDA has granted AOC 1001 Fast Track designation.

In May 2023, the FDA eased the partial clinical hold on AOC 1001, allowing Avidity to double the number of participants in the MARINA-OLE study receiving 4 mg/kg of AOC 1001 from 12 to 24 participants. Data from the 12 participants dose-escalated from 2 mg/kg to 4 mg/kg of AOC 1001 as part of the easement of the partial clinical hold showed no neurological events and no MRI changes following dosing. The company continues to work as quickly as possible to resolve the partial clinical hold.

The AOC 1001 data from the phase 1/2 MARINA trial and MARINA open-label extension (MARINA-OLE) study will be highlighted in an oral presentation at the 28th Annual Congress of the World Muscle Society in Charleston, South Carolina and can be found on Avidity’s website on the Publications page.

The new AOC 1001 data presented today demonstrating improvements in muscle strength and patient reported outcomes add to the previously reported positive topline data showing improvements in myotonia and mobility.

“Data from MARINA and MARINA-OLE reinforce our belief in the potential of AOC 1001 to become an effective treatment option for people living with DM1, a devastating rare disease for which there are no treatment options available. With this robust data package, we are finalizing the phase 3 study design and global regulatory path for AOC 1001 and look forward to sharing a first look at efficacy data from the MARINA-OLE study in the first half of 2024,” said Sarah Boyce, president and CEO at Avidity. “In addition to our DM1 program, we continue to advance our DMD and FSHD clinical development programs and plan to report data from all three of our programs by mid-2024 while continuing to expand our discovery and development pipeline.”

Photo: Sarah Boyce, president and CEO at Avidity