FDA Awards Orphan Drug Designation to Losmapimod for Treatment of FSHD

Although there are no approved therapies for FSHD, researchers at Fulcrum Therapeutics discovered that inhibition of p38α/β reduced expression of the DUX4 gene in muscle cells derived from patients with FSHD.

Fulcrum Therapeutics has received orphan drug designation for losmapimod, a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor for the treatment of facioscapulohumeral muscular dystrophy (FSHD).1

FSHD is a rare disease characterized by muscle weakness and atrophy. Symptoms typically appear in early adulthood, but can begin in infancy or later in adulthood. Progression of the disease is typically slow, and it is estimated to effect between 4 and 10 per 100,000 people. It is caused by abnormal expression of the DUX4 gene.2

In the reduction of DUX4 expression, p38α/β inhibitors such as losmapimod play an important role. Although there are no approved therapies for FSHD, researchers at Fulcrum Therapeutics discovered that inhibition of p38α/β reduced expression of the DUX4 gene in muscle cells derived from patients with FSHD.

The company announced preliminary results from a Phase 1 clinical trial in October 2019, which found that losmapimod was generally well-tolerated and achieved dose-dependent concentrations in plasma and muscle believed to be adequate for efficacy based on preclinical pharmacology studies.

The drug was evaluated in over 3500 subjects in clinical trials across multiple other indications. No safety signals were attributed to losmapimod in any of the trials, and Fulcrum is currently conducted Phase 2 trials investigating the safety, tolerability, and efficacy of losmapimod to treat the root cause of FSHD.

REFERENCES

  • Fulcrum Therapeutics Receives Orphan Drug Designation for Losmapimod in Facioscapulohumeral Muscular Dystrophy (FSHD) and Announces Expanded Patent Portfolio [news release]. Cambridge, MA; Jan 29, 2020. GlobeNewswire. https://www.globenewswire.com/news-release/2020/01/29/1976751/0/en/Fulcrum-Therapeutics-Receives-Orphan-Drug-Designation-for-Losmapimod-in-Facioscapulohumeral-Muscular-Dystrophy-FSHD-and-Announces-Expanded-Patent-Portfolio.html. Accessed Jan 29, 2020.
  • Rare Disease Database: Facioscapulohumeral Muscular Dystrophy. National Organization for Rare Disorders, rarediseases.org/rare-diseases/facioscapulohumeral-muscular-dystrophy/. Accessed Jan 29, 2020.