Fulcrum Launches Phase 2b Trial of Losmapimod for FSHD

Fulcrum Therapeutics announced it has launched ReDUX4, a Phase 2b clinical trial designed to assess the safety and efficacy of losmapimod, an investigational treatment for facioscapulohumeral muscular dystrophy (FSHD) in patients with a genetically confirmed diagnosis of FSHD.

The Phase 2b ReDUX4 trial (NCT04003974) is recruiting participants at clinical sites in the United States, Canada, and the European Union. Fulcrum is expecting top-line data from ReDUX4 to be available by the end of 2020.

Losmapimod is a selective inhibitor of p38α/β mitogen-activated protein kinases (MAPK), a class of enzymes involved in acute inflammation and cells’ response to injury. The compound was in-licensed by Fulcrum after the company discovered its ability to reduce the activity of the DUX4 gene, the root cause of FSHD, during preclinical studies using patient-derived muscle cells.

“We are excited to evaluate losmapimod’s efficacy and safety in FSHD, a disease for which there are currently no approved treatments. Initiating ReDUX4 is a significant milestone that brings us a step closer to our goal of improving the lives of patients and families who are impacted by FSHD,” Robert J. Gould, PhD, president and chief executive officer of Fulcrum, said in a press release.

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The 24-week, multi-center, randomized, double-blind, placebo-controlled, Phase 2b ReDUX4 trial (NCT04003974) will enroll patients with a confirmed diagnosis of FSHD type 1 (FSHD1), the most common form of FSHD, accounting for approximately 95% of cases.

Patients will participate in the trial for approximately 29 weeks, which includes an initial four-week screening period, a 24-week treatment period, and a one-week safety follow-up period. To be eligible to participate in the study, patients must have received a genetic diagnosis of FSHD1 before undergoing magnetic resonance imaging (MRI) during the trial’s screening period and before providing a muscle biopsy sample at the study’s baseline.

After enrollment, all study participants will be randomly assigned to receive either losmapimod or a placebo (four pills of 7.5 mg, taken two at a time, twice a day) for 24 weeks.

The study’s primary endpoint will be to assess the efficacy of losmapimod in reducing or preventing the overactivity of DUX4, which will be measured by the amount of DUX4 gene transcripts (the molecules that serve as the template for the production of a protein) found in skeletal muscle biopsies of patients.

Secondary endpoints will include assessing the safety and tolerability of losmapimod, measuring the levels of the compound on patients’ plasma and muscle cells, and evaluating its target engagement (the drug’s ability to interact with its therapeutic target) in blood and skeletal muscle.

The company is also preparing to launch a 52-week, open-label, Phase 2 trial (NCT04004000) to assess the effectiveness, safety, and tolerability of losmapimod in FSHD1 patients.