Fulcrum Therapeutics Secures Global Rights to GSK’s Losmapimod for Development in Facioscapulohumeral Muscular Dystrophy (FSHD)

VCBeat (WeChat Official Account: vcbeat) learned from foreign media that on April 23, U.S. local time, Fulcrum Therapeutics, a biotechnology company headquartered in Cambridge, Massachusetts, announced an exclusive global licensing agreement with GlaxoSmithKline (GSK), securing the global development and commercialization rights to GSK’s new drug, Losmapimod. It is reported that Fulcrum Therapeutics plans to apply Losmapimod to the treatment of facioscapulohumeral muscular dystrophy (FSHD), a rare and severely disabling genetic disorder for which there are currently no approved treatments.

Under the terms of the agreement, GSK acquired a portion of Fulcrum Therapeutics’ preferred shares and is eligible to receive future milestone payments and royalties from Fulcrum Therapeutics. In addition to obtaining global development and commercialization rights for losmapimod, Fulcrum Therapeutics also received a supply of drug product and materials necessary for the clinical trials of losmapimod. Furthermore, Fulcrum Therapeutics has submitted Investigational New Drug (IND) applications to the FDA for losmapimod and secured exclusive licenses to all relevant patents and data.

Losmapimod is a selective p38α/β MAPK inhibitor, originally developed by GSK and now licensed to Fulcrum Therapeutics. GSK extensively tested losmapimod in multiple clinical trials but never evaluated it in muscular dystrophy.

Facioscapulohumeral Muscular Dystrophy (FSHD) is one of the most common forms of muscular dystrophy, with a prevalence in the general population ranging from approximately 1/20,000 to 1/8,000. Symptoms of FSHD typically manifest in adulthood, beginning with weakness in the facial muscles that impairs the ability to smile. The condition then progresses from the upper body to the lower body, ultimately resulting in the inability to raise the arms above shoulder level or to perform sit-to-stand movements. Individuals with FSHD often experience difficulty carrying out normal daily activities and may suffer from severe fatigue and pain.

Fulcrum Therapeutics discovered that the silencing of the DUX4 gene during the early stages of embryonic development triggers FSHD, and that p38α/β MAPK inhibitors can effectively suppress DUX4 gene expression. Leveraging its unique insights into the pathogenesis of FSHD, Fulcrum Therapeutics sought existing p38α/β MAPK inhibitors for the treatment of FSHD. Ultimately, losmapimod, developed by GSK, was identified by Fulcrum Therapeutics as the most promising compound for treating FSHD.

Fulcrum Therapeutics has demonstrated in trials that the inhibitor losmapimod can effectively modulate DUX4 gene expression. The company has evaluated losmapimod in more than 3,500 healthy volunteers and patients across 24 clinical trials assessing multiple indications, ultimately finding that losmapimod effectively downregulates DUX4 gene expression and restores healthy muscle in patients without affecting myogenesis.

“Losmapimod has the potential to become the first approved therapy capable of curing FSHD. It can slow or halt the progression of muscle weakness, which will significantly improve patients’ quality of life,” said Dr. Robert J. Gould, Chief Executive Officer of Fulcrum Therapeutics. “We believe our unique therapeutic approach, which treats disease by balancing gene expression, holds promise for benefiting more patients suffering from severe genetic disorders.”

Fulcrum Therapeutics expects to conduct a Phase 2b clinical trial of losmapimod in patients with FSHD at multiple clinical sites in the United States and Europe by mid-2019.

(Compiled by Wang Chan)