The US Food and Drug Administration (FDA) has eased a partial clinical hold on Avidity Biosciences’s AOC 1001. The San Diego-based biopharma company will be allowed to double the number of participants with myotonic dystrophy type 1 (DM1) in its Phase II open-label study receiving 4 mg/kg of AOC 1001.

AOC 1001 consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA and aims to reduce the levels of disease-related mRNA called DMPK.

DM1 is a progressive and often fatal disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA.

The FDA put a partial hold on the 4 mg/kg dose last September after the company reported a rare serious adverse event in a single subject enrolled into a randomised Phase I/II MARINA trial (NCT05027269).

In addition to a doubled enrolment for the 4 mg/kg dose cohort, the FDA is also allowing new participant enrolment for a 2 mg/kg dose. The data from the MARINA open-label extension (MARINA-OLE) trial (NCT05479981) will be pivotal for the next development steps of AOC 1001.

“This positive step forward in our discussions with FDA provides the opportunity to gather additional data on the 2-4 mg/kg dose range of AOC 1001 while, in parallel, finalising our Phase III study design and aligning with health authorities on a global regulatory path for AOC 1001,” said Sarah Boyce, president and chief executive officer at Avidity.

The aim of the MARINA-OLE trial is to continue to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AOC 1001 in participants who were enrolled into the Phase I/II MARINA trial. The estimated enrolment is 44 participants, according to the listing.

The primary endpoint of the trial is measuring the number and severity of treatment-emergent adverse events. The company expects to release topline data from the MARINA-OLE trial by the end of 2023.

Phase I/II topline results

In April 2023, Avidity announced positive topline results from the Phase I/II MARINA trial. The data analysis showed that AOC 1001 achieved directorial improvements in various functional endpoint assessments of myotonia, strength and mobility. 

Myotonia, impaired relaxation of muscles, was measured by video opening time (vHOT), while measures of strength included the Quantitative Muscle Testing (QMT) total score which is based on six muscle groups from both the upper and lower body. Mobility was assessed by the 10m walk run test and a Timed Up and Go test.

AOC 1001 also demonstrated a meaningful reduction of DMPK and showed broad splicing improvements in more than a thousand genes impacted by DM1.

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