Regeneron drug on track to be second FOP treatment

There is only one approved drug for ultra-rare disease fibrodysplasia ossificans progressiva (FOP) on the US market, but Regeneron is hoping to add to that tally.

The US company has reported positive topline results from a phase 3 trial of its FOP candidate garetosmab, an anti-activin A antibody, and is now hoping to file for approval of the drug with the FDA before the end of the year.

If it reaches the market, garetosmab will join Ipsen's oral RAR gamma agonist Sohonos (palovarotene) among FDA-approved therapies for FOP, a life-shortening and highly debilitating disorder in which bony lesions – known as heterotopic ossifications (HO) – are laid down in muscles, tendons, and ligaments. It affects around 400 people in the US and 900 worldwide.

Sohonos was launched in the US in 2023 with a list price of $624,000 per year at a 5 mg daily dose, although the cost can vary depending on patients' weight, and brought in just over €8 million (around $9.5 million) in sales in the first six months of this year, a fall of 20%.

The marketing application for Sohonos in the EU was rejected in 2023, and the drug's growth has been held back by a side-effect profile that in trials led almost one in 10 patients to discontinue treatment.

Regeneron said that both doses of garetosmab tested in the OPTIMA trial, 3 mg/kg and 10 mg/kg, were "highly efficacious" in reducing the number of new bone lesions compared to placebo, achieving 94% and 90% reductions, respectively.

That might suggest greater efficacy than was observed in the open-label MOVE trial of Sohonos, which compared the drug to historic data in the progression of FOP and showed a 60% reduction in new HO volume. Ipsen isn't resting on its laurels, however, and is working on a follow-up FOP drug, activin receptor blocker fidrisertib, which is in the phase 2 FALKON trial.

The independent data monitoring committee for OPTIMA has recommended that all patients switch to garetosmab as soon as possible, according to Regeneron, which has said that it believes activin A plays a key role in the development of bony lesions in FOP.

"Heterotopic ossification is a hallmark of FOP, a horrific disease in which muscles, tendons, and ligaments are progressively replaced by bone, gradually incapacitating patients," said Prof Richard Keen of the Royal National Orthopaedic Hospital in London, UK, the primary investigator for OPTIMA.

He added that the results "clearly illustrate the potential of garetosmab to alter the disease and reduce new lesions that define this condition," and pointed out that garetosmab is "the first and only investigational therapy to demonstrate a dramatic reduction in both the number and volume of abnormal bone lesions."