Phase 2b Trial of Fulcrum’s Oral FSHD Treatment, Losmapimod, Fully Enrolled

Fulcrum Therapeutics announced that its Phase 2b trial assessing the safety and efficacy of losmapimod, an investigational oral treatment for facioscapulohumeral muscular dystrophy (FSHD), is fully enrolled.

The trial (NCT04003974), called ReDUX4, started recruiting patients at clinical sites in the U.S., Canada, and Europe last year. It is evaluating 24 weeks of treatment with losmapimod (four 7.5 mg tablets, taken two at a time, twice a day), against a matching placebo, in about 80 adults with a confirmed FSHD diagnosis.

Its main goal is to assess losmapimod’s ability to reduce or prevent the overactivity of the DUX4 gene, the root cause of FSHD.  Efficacy which will be measured by the amount of DUX4 transcripts found in muscle biopsies of patients. (Transcripts are the molecules that cells use as a template to produce proteins.)

Secondary goals include assessing the medication’s safety and tolerability, measuring its levels in patients’ blood plasma and muscle cells, and evaluating its target engagement (the drug’s ability to interact with its intended therapeutic target) in blood and skeletal muscle.

“We want to express our gratitude to all the patients, investigators and caregivers participating in this global trial. Completing patient recruitment for ReDUX4 is a testament to the commitment of the patient community, clinical investigators, our partners, and our Fulcrum team to address the critical needs of patients with FSHD and is a significant milestone,” Robert J. Gould, PhD, president and chief executive officer of Fulcrum Therapeutics, said in a press release.

Fulcrum also announced it has started dosing patients who completed ReDUX4  and moved into the trial’s open-label, Phase 2 extension study (NCT04264442).

Here, all will be treated with losmapimod at a total of 30 mg daily — four 7.5 mg tablets, taken two at a time, twice a day — for 52 weeks (about one year). The medication should be taken with food.

This extension study’s main goal is to evaluate the long-term safety and tolerability of losmapimod. Additional goals include assessing the compound’s target engagement in the blood and skeletal muscle, as well as its levels in patients’ plasma at specific time points.

The open-label extension study is expected to conclude in January 2021. Fulcrum anticipates announcing topline data from ReDUX4 later this year.

“We remain on track to report topline data on the primary endpoint in the third quarter of this year,” Gould said.

Losmapimod is a selective inhibitor of p38 alpha and p38 beta. These two proteins belong to a family of enzymes called mitogen-activated protein kinases (MAPKs), which are important for the regulation of DUX4 activity.

It was recently designated an orphan drug by the U.S. Food and Drug Administration as a potential FSHD treatment, a designation that provides Fulcrum with financial incentives to advance its development for this patient group.