FDA approves Mirum's oral drug for rare disease FOP
Patients with fibrodysplasia ossificans progressiva (FOP) in the US will soon have the option of treatment with another daily pill after the FDA approved Mirum Pharma's ALK2 inhibitor, Atebrioz, for the rare bone disease.
Atebrioz (zilurgisertib) is the third drug to be approved in the US 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 has been cleared for use in children aged 12 and over and adults.
Ipsen's oral RAR gamma agonist Sohonos (palovarotene) was the first to be greenlit for FOP in 2023 but has underperformed commercially, held back by the failure to win approval in the EU, age restrictions on its use, safety issues leading to high discontinuation rates, and modest efficacy.
Sohonos was joined earlier in August this year by Regeneron's once-monthly intravenous infusion Pasatru (garetosmab), which seems to offer a step up in efficacy, achieving a 90% or greater reduction in new bony lesions at 56 weeks, compared to just a 60% reduction in Sohonos' pivotal trial.
Mirum has won FDA approval for Atebrioz on the back of the phase 2 PROGRESS study, which showed a near-100% reduction in new growths, and suggests Regeneron's drug could face stiff competition in the market early in its rollout. In absolute numbers, Mirum's drug was associated with a 3.2 cm3 reduction in new bone volume, compared to an increase of 24.6 cm³ with placebo.
Atebrioz also cut the number of patients developing new lesions by 81%, with only 3.1% of patients on the drug developing a new lesion compared to 16.7% of the control group.
Along with the more patient-friendly dosing that avoids the need for clinic visits, Atebrioz also seems to have the edge on safety, with zero treatment discontinuations or dose reductions, while Pasatru does carry a risk of acute tissue infections, which can be mitigated with step-down dosing.
Pricing will likely be a key factor as the new therapy jostles for market share. Pasatru has an average annual list price of $1.4 million, with a range from a round $700,00 to $2.1 million, depending on patient weight. Mirum hasn't revealed its pricing plans yet, but analysts cited by Reuters speculate that it may opt to charge around $750,000 per year, which would deliver sales of around $150 million at peak.
Atebrioz – which Mirum licenses from Incyte – is also under review in the EU. The FDA approval has earned the company a rare paediatric disease priority review voucher (PRV), which can be sued to shorten a drug review and can command $100 million to $200 million if sold to another company.
Extensions of the PROGRESS trial testing Atebrioz in younger children with FOP, with one cohort enrolling patients aged six to 11 and a third in the over-twos.
