FDA OKs Trial of Investigational DM1 Therapy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
Edgewise BMD therapy EDG-5506/musculardystrophynews.com/FDA grants fast track designation


The U.S. Food and Drug Administration (FDA) has cleared Avidity Biosciences to start a Phase 1/2 clinical trial testing the company’s investigational therapy AOC 1001 in adults with myotonic dystrophy type 1 (DM1).

“The FDA clearance to proceed with our Phase 1/2 clinical trial for AOC 1001 is a significant milestone for Avidity as we move into the clinic,” Sarah Boyce, president and CEO of Avidity, said in a press release.

“We are continuing to engage with the DM1 patient, advocate and physician community as we actively work to get the trial up and running,” Boyce added.

Recommended Reading
Open Enrollment Sign with Stethoscope

DMD Trial Testing Oral ASP0367 Recruiting Boys 8–16 in US

The upcoming trial, called MARINA, is expected to enroll about 44 adults with DM1. It will be a randomized, double-blind, placebo-controlled study. That means some participants will get the active medication and others will be given placebo, and neither the trial participants nor the healthcare workers administering the product will know which is which.

The trial’s main goal is to evaluate the safety and tolerability of different doses of the therapy. Some participants will receive just one dose, while others will be given multiple doses. AOC 1001 is designed to be administered intravenously (directly into the bloodstream).

The trial also will assess whether the investigational therapy can decrease the levels of DMPK mRNA. DM1 is caused by mutations in the DMPK gene that result in cells making a toxic, abnormally long mRNA (messenger RNA, an intermediate molecule that is complementary to one of the DNA strands of a gene).

AOC 1001 is designed to decrease the levels of this toxic mRNA, and has shown promise in preclinical models. The therapy consists of a short interfering RNA (siRNA) molecule, which can target and degrade the toxic mRNA, that is attached to an antibody that ferries the siRNA to the cells where it is needed. AOC 1001 belongs to a new class of RNA therapeutics called antibody oligonucleotide conjugates (AOCs).

The upcoming clinical trial will not be powered to assess functional benefit. Nonetheless, measures of mobility and muscle strength, as well as patient-reported outcomes and assessments of quality of life, will be explored in the MARINA trial. Participants will have the opportunity to enroll in an open-label extension study at the end of the trial.

Avidity is planning to conduct a preliminary assessment of safety, tolerability, and certain biological markers in approximately half of the study participants in the latter part of 2022.

AOC 1001 recently was designated an orphan drug by the FDA for the treatment of DM1. This designation is given to investigational medications with the potential to substantially improve care for rare diseases. It confers certain benefits to the therapy’s developer, most notably seven years of market exclusivity if the treatment eventually is approved.