Sanofi is betting $80 million upfront on a GSK castoff ahead of a phase 3 readout. Fulcrum Therapeutics took the other side of the deal, handing Sanofi ex-U.S. rights to a rare disease candidate that is leading Roche in a race to market.
The deal will see Sanofi pay the upfront fee and commit up to $975 million in milestones for the rights to the p38 inhibitor losmapimod outside of the U.S. Fulcrum expects to report top-line data from a 260-subject phase 3 trial of the molecule in the progressive muscle wasting disorder facioscapulohumeral muscular dystrophy (FSHD) in the fourth quarter.
Massachusetts-based Fulcrum designed its trial to support authorization in the U.S. and overseas. Sanofi plans to seek approval in Europe, Japan and other geographies, while Fulcrum is retaining full rights in the U.S.
If losmapimod gets the green light, it could become the first approved therapy for a disease that affects around 30,000 people in the U.S. alone. Roche is developing a myostatin inhibitor in FSHD, but Fulcrum CEO Alex Sapir told attendees at an investor event in April that losmapimod has a two- to three-year head start. Avidity and Arrowhead Pharmaceuticals have antibody-oligonucleotide complexes in clinical development for FSHD.
The market is potentially lucrative. The U.S. patient population is larger than for other neuromuscular diseases, such as Friedreich’s ataxia, but Fulcrum left early talks with payers believing losmapimod can command a price of hundreds of thousands of dollars. Sapir cited Biogen’s Friedreich’s ataxia treatment Skyclarys, which has an annual list price of $370,000, as the closest comparison to losmapimod.
Phase 3 data will shape whether losmapimod can command such a price. The drug failed a phase 2b trial in FSHD in 2021, but Fulcrum looked past the primary endpoint miss and forged ahead into a pivotal study, wrapping up enrollment in September 2023. The biotech’s confidence is based on phase 2b data showing losmapimod may slow disease progression and improve function in FSHD patients.
Fulcrum rescued the molecule from GSK’s vault in 2019. At GSK, losmapimod failed a phase 3 trial in patients with acute coronary syndrome and a midstage study in chronic obstructive pulmonary disease. But Fulcrum spotted a different opportunity for the molecule, latching on to the potential to block DUX4, a gene that underpins FSHD, by inhibiting p38.
The biotech handed GSK stock and a chance to receive up to $37.5 million in milestones for the asset. Sanofi and Fulcrum will split future global development costs down the middle. Fulcrum will receive tiered escalating royalties starting in the low-teens on annual net sales of losmapimod outside the U.S.