Losmapimod has favorable safety profile in facioscapulohumeral muscular dystrophy

Key takeaways:

• Safety and tolerability of losmapimod were assessed in 108 people with facioscapulohumeral muscular dystrophy.
• No serious adverse events or treatment discontinuations due to adverse events were recorded.

DENVER — Losmapimod treatment for those with facioscapulohumeral muscular dystrophy led to no serious adverse events across three clinical trials, according to a poster at the American Academy of Neurology annual meeting.

“This is the third most-common muscular dystrophy and affects about 20,000 people in the United States, but the number is not exactly known because not all patients are diagnosed genetically,” Mihaela Levitchi Benea, MD, executive director of medical affairs at Fulcrum Therapeutics in Massachusetts, told Healio. “There is no treatment for this disease.”

To address the lack of treatment, Levitchi Benea and colleagues wanted to assess the safety and tolerability of losmapimod (Fulcrum Therapeutics), a small molecule p38 alpha/beta MAPK inhibitor, in facioscapulohumeral muscular dystrophy (FSHD) in one completed phase 1 study and two ongoing phase 2 studies in their respective open-label extension periods.

The studies included 108 adult participants with a genetically diagnosed confirmation of the condition, a Clinical Severity Score of 2 to 4 and who underwent an MRI for muscle biopsy.

In the phase 1 clinical trial (FIS 001-2018), participants were administered losmapimod in either 7.5 mg or 15 mg or placebo in a 2:2:1 ratio orally twice a day for 14 days, with an open-label, repeated-dose extension for 14 days where five participants were given 15 mg losmapimod twice daily.

In study FIS-001-2019 (phase 2 OLE, 52 weeks), 14 individuals were given 15 mg tablets of losmapimod twice a day, followed by an extension period that included 12 participants.

The other phase 2 trial FIS-002-2019 (ReDUX4, 48 weeks) featured 80 participants randomized 1:1 to receive at least one dose of losmapimod 15 mg twice daily for up to 96 weeks or placebo.

Adverse events observed during the studies were mild to moderate in severity and most resolved with continued dosing. The most common events reported were eczema, dry skin, alanine aminotransferase increase, rash, headache and myalgia.

Dosing was paused for 14 days in four participants (3 in FIS 001-2019 and 1 in FIS-002-2019) due to COVID-19.

Data further revealed no drug-related serious adverse events, deaths, discontinuations due to adverse events, or clinically significant changes in vital signs or clinical laboratory results across the studies.

“With our current benefit-risk assessment on losmapimod, we will continue to develop the drug for the treatment of [facioscapulohumeral muscular dystrophy],” Levitchi Benea told Healio. “We are looking to generate more data from a (planned) phase 3 as well as the extension studies.”