Fulcrum bags failed GSK drug, plots muscle-wasting pivot

GlaxoSmithKline has offloaded the global rights to failed cardiovascular disease drug losmapimod to Fulcrum Therapeutics. Fulcrum plans to reposition the p38 mitogen-activated protein kinase inhibitor as a treatment for facioscapulohumeral muscular dystrophy (FSHD).

Losmapimod hit the skids late in 2015 when GSK wrapped up a phase 3 trial in patients with acute coronary syndrome. The study found losmapimod was no better than placebo at preventing major adverse cardiovascular events, deterring GSK from further investment and seemingly consigning the drug to the scrapheap.

Now, Fulcrum wants to write a new chapter in the story of losmapimod. The biotech, which raised an $80 million series B round last year, has identified inhibition of p38 as a way to block expression of DUX4, a gene that underpins progressive muscle wasting disorder FSHD.

That led Fulcrum to search for drugs that inhibit p38 and ultimately to losmapimod. While GSK never tested losmapimod in muscular dystrophies, Fulcrum has assessed the candidate in patient-derived cell models and emerged with data showing it downregulates DUX4 and restores a healthy muscle phenotype.

Fulcrum was encouraged enough by the data to strike a deal with GSK and commit to move the drug into a midphase trial. 

“Losmapimod is a foundational clinical asset for Fulcrum that has the potential to become the first approved therapy that targets the root cause of FSHD. Fulcrum believes losmapimod has the potential to slow or halt the progressive muscle weakness that characterizes the condition, which would significantly improve patients’ quality of life,” Fulcrum CEO Robert Gould said in a statement.

GSK relinquished the worldwide rights to losmapimod, plus existing drug materials for use in clinical testing, in return for a high-single-digit stake in Fulcrum.

Having closed the deal, Fulcrum plans to start a phase 2b trial of losmapimod in FSHD around the middle of the year. Fulcrum is able to start testing losmapimod in FSHD at such an advanced phase of development because of the data GSK generated in other indications, which show the drug is well tolerated. 

The upshot is Fulcrum has leapfrogged toward the front of the race to develop a treatment for FSHD. Other runners include Acceleron and Evotec-backed Facio Therapies.