FDA Grants Fast Track Designation to Avidity AOC 1001 for the Treatment of DM1

The U.S. Food and Drug Administration granted Fast Track designation to Avidity Biosciences’ experimental antibody oligonucleotide conjugate AOC 1001 for the treatment of myotonic dystrophy type 1.

Photo: Sarah Boyce, president and CEO of Avidity

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, but patients can also 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 treatments for patients living with DM1.

Fast Track designation enables more frequent interactions with the FDA to expedite the development and review process for drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

“DM1 is an underrecognized, progressive and often fatal disease with no therapeutic options. Fast Track designation for AOC 1001 underscores this unmet need and allows us to expeditiously work with FDA to potentially deliver this first-in-class therapy to people living with DM1 as quickly as possible,” said Sarah Boyce, president and CEO of Avidity.

AOC 1001, Avidity’s lead program 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. In preclinical studies, AOC 1001 had a favorable safety profile that supports advancement into the clinic. The FDA has cleared Avidity to proceed with the phase 1/2 MARINA study of AOC 1001 in adults with DM1. FDA and EMA have granted Orphan designation for AOC 1001 and the FDA has granted AOC 1001 Fast Track designation.

The MARINA trial is a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial expected to enroll approximately 44 adults with DM1. The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 administered intravenously. The MARINA trial will assess the activity of AOC 1001 across key biomarkers. Though the phase 1/2 trial is not powered to assess functional benefit, it will explore the clinical activity of AOC 1001 including measures of mobility and muscle strength as well as patient reported outcomes and quality of life measures. Patients will have the option to enroll in an open label extension study at the end of the post-treatment period. In the second half of 2022, Avidity plans to conduct a preliminary assessment of safety, tolerability and key biomarkers in approximately half of the study participants.

Author: Rare Daily Staff