Higher doses of AOC 1001 on tap for patients in MARINA-OLE trial

FDA approves plan for the experimental myotonic dystrophy type 1 therapy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Avidity Biosciences is planning to double the dosage of AOC 1001 being given to a dozen people with myotonic dystrophy type 1 (DM1) who are receiving the experimental therapy in the MARINA-OLE clinical trial.

The U.S. Food and Drug Administration (FDA) had placed a partial clinical hold on the trial in September, after a serious health problem was reported in a patient given the highest tested dose (4 mg/kg) of AOC 1001. Now, Avidity announced the FDA has eased the hold, allowing an increase in the number of patients given the high dose.

The FDA also has allowed enrollment of more participants for a lower dose (2 mg/kg). According to the company, data from MARINA-OLE will be used to help design a Phase 3 clinical trial to test AOC 1001 further.

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“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, finalizing our Phase 3 study design and aligning with health authorities on a global regulatory path for AOC 1001,” Sarah Boyce, Avidity’s president and CEO, said in a press release.

“We are focused on advancing AOC 1001 into a pivotal trial as quickly as possible as we know that the patient community is desperate for a treatment,” Boyce added. “We are extremely grateful to the DM1 community for their trust, support and ongoing partnership.”

In DM1, mutations in the DMPK gene result in an abnormally long messenger RNA (mRNA) molecule being produced when the gene is read. This abnormally long intermediary molecule forms toxic clumps in muscle cells, driving disease progression. AOC 1001, which is administered via infusion into the bloodstream, is designed to reduce the levels of this toxic mRNA. It does so by having a siRNA — a specialized RNA molecule —  that can target mRNA for destruction.

Avidity sponsored a Phase 2 trial called MARINA (NCT05027269) which concluded with 38 adult participants with DM1. A few participants were given a single infusion of AOC 1001 at a low dose of 1 mg/kg. The other participants received three infusions of AOC 1001, at 2 mg/kg or 4 mg/kg, or a placebo. Participants were followed for about six months.

Favorable safety profile

The study’s main goal was to evaluate the safety of AOC 1001, and top-line results showed a favorable safety profile — most side effects were rated as mild or moderate in severity. While the study was not designed to assess efficacy, top-line data also suggested that patients given AOC 1001 tended to report improvements across a range of functional measures.

All but two participants who completed the MARINA trial continued into MARINA-OLE (NCT05479981), a two-year open-label extension trial in which all participants are being treated with AOC 1001 at 2 mg/kg or 4 mg/kg. With the new announcement, 12 patients on the 2 mg/kg dose will be moving to the 4 mg/kg dose, doubling the number of patients on the high dose. The remaining participants will remain on their current dose.

Initial data from MARINA-OLE are expected by the end of this year, according to Avidity.

“We recently announced positive topline data for AOC 1001 demonstrating functional improvement across multiple clinical outcome measures and look forward to sharing a first look at data from the MARINA-OLE study at the end of this year,” Boyce said.

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