Phase 1 Results Support Losmapimod as FSHD Treatment

Final results of a Phase 1 clinical trial support the safety of losmapimod and suggest its effectiveness as a treatment for facioscapulohumeral muscular dystrophy (FSHD).

The data, “Phase 1 Clinical Trial of Losmapimod in Facioscapulohumeral Muscular Dystrophy (FSHD): Safety, Tolerability and Target Engagement,” were presented by Michelle Mellion, MD, at a virtual session of the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference. Mellion is the senior medical director at Fulcrum Therapeutics, the company developing losmapimod.

More than 90% of cases of FSHD are caused by mutations that lead to hyperactivity of the gene DUX4. Losmapimod is given orally to selectively block the p38 alpha and p38 beta proteins that regulate DUX4.

The primary goal of the Phase 1 trial was to determine the safety and  tolerability of losmapimod. The trial included three groups. In the first, eight of 10 healthy volunteers were given a 7.5 mg dose of the treatment, followed by a washout period, then a 15 mg dose. The other two participants received a placebo.

In the second group, 15 people with FSHD were assigned randomly to either losmapimod or placebo. The therapy was given at doses of either 7.5 mg or 15 mg, taken twice a day for 14 days.

The third group had five participants with FSHD, who were given 15 mg losmapimod twice per day.

Safety and pharmacology results were similar in healthy volunteers and individuals with FSHD. The overall safety profile of losmapimod was consistent with previous data from more than 3,500 healthy volunteers and patients treated with this therapy across other indications, Fulcrum said in a press release. No serious adverse events (SAEs) were reported.

Analyses of samples of the participants’ blood and muscle tissue suggested the losmapimod was engaging its target in a dose-dependent manner. Treatment doses in blood and muscle also were higher with the greater dose (15 mg).

“Losmapimod was well tolerated with no SAEs reported and achieved dose-dependent exposure [levels] in plasma and muscle at concentrations predicted by pre-clinical models demonstrating efficacy by reducing DUX4 activity,” the investigators wrote.

These data also support the selection of a twice-daily 15 mg dose of losmapimod, which is being used in an ongoing Phase 2b clinical trial called ReDUX4 (NCT04003974), investigating the therapy’s safety and effectiveness.

ReDUX4 completed enrollment last month, with results expected in early 2021. Participants in ReDUX4 can continue on the therapy in a Phase 2 extension study (NCT04264442).

As a potential treatment for FSHD, losmapimod recently was designated an orphan drug by the U.S. Food and Drug Administration, which gives Fulcrum financial incentives and other forms of support to successfully conduct clinical development.