In an investor news release from biopharmaceutical company Avidity Biosciences, Inc., the company shared that the FDA placed a partial clinical hold on new enrollment for the Phase 1/2 MARINA clinical study. Within the study, researchers are evaluating AOC 1001 for adult patients with myotonic dystrophy type 1 (DM1). Although the trial will not be accepting any new participants, those who are involved in the study, or the open-label extension study, can continue their dosing schedule. Those in the Phase 1/2 MARINA trial may also move on to the open-label extension for AOC 1001 treatment.

According to the FDA, a partial clinical hold is:

a delay or suspension of only part of the clinical work requested under the IND (e.g., a specific protocol or part of a protocol is not allowed to proceed; however, other protocols or parts of the protocol are allowed to proceed under the IND).

In the case of the Phase 1/2 MARINA trial, the partial clinical hold was placed on the trial following a serious adverse reaction. The patient who had this reaction received 4mg/kg AOC 1001. Currently, Avidity is working with the FDA to determine what happened and to ensure that the trial is as safe as possible moving forward.

AOC 1001: A Brief Overview

Within the study, researchers are evaluating AOC 1001. In a late 2021 news release from Avidity, AOC 1001 is described as being:

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.

AOC 1001 has received both Fast Track and Orphan Drug designations from the FDA.

Myotonic Dystrophy types 1 and 2 (DM1 and DM2)

Myotonic dystrophy is a rare multisystem disorder characterized by progressive muscle wasting and weakness. There are two main forms which often have overlapping signs and symptoms. DM1 results from an abnormally expanded section of DMPK on chromosome 19. It is often more severe than type 2. Muscle weakness from DM1 usually affects the face, lower legs, hands, and neck. Alternately, DM2 results from an abnormally expanded section of ZNF9 on chromosome 3. Muscle weakness in this form primarily affects the neck, hips, elbows, and shoulders. Although myotonic dystrophy is rare, it is the most common form of adult-onset muscular dystrophy. Symptoms and characteristics can (but do not always) include:

• Voluntary muscle weakness
• Inability to relax muscles at will (myotonia)
• Learning disabilities and/or cognitive impairment
• Apathy
• Difficulty swallowing
• Gallstones
• Constipation
• Respiratory issues
• Abnormal heart rhythm
• Pregnancy and labor complications
• Cataracts
• Speech, hearing, and vision difficulties