The US Food and Drug Administration (FDA) has approved of palovarotene (Sohonos) to treat fibrodysplasia ossificans progressiva (FOP). More specifically, the orphan drug is indicated to treat the reduction in volume of new heterotopic ossification in females aged 8 years and older and males aged10 years and older with FOP.

FOP is genetic disorder characterized by new bone formation outside of the normal skeletal system, like in soft connective tissues, a process known as heterotopic ossification, which can be preceded by painful soft-tissue swelling or “flare-ups”. Heterotopic ossification, once formed, is irreversible and leads to loss of mobility and shortened life expectancy. FOP is a particularly painful and deliberating condition. Often, early death can be the result of Bone forming around the ribcage leading to breathing problems and cardiorespiratory failure.

FOP is an ultra-rare condition that afflicts about 400 people in the US and 900 people globally.

Palocarotene is an oral, selective retinoic acid receptor gamma (RARγ) agonist designed to prevent/reduce heterotopic ossification.

The FDA approval was largely based on data from the open-label Phase III MOVE trial. Data from that study was published in the Journal of Bone and Mineral Research and included 107 patients who received oral palovarotene compared with untreated individuals in a FOP natural history study. The study demonstrated that treatment with palovarotene reduced annualized heterotopic ossification volume compared to standard of care. The mean annualized new heterotopic ossification volume was 60% lower in palocarotene-treated patients versus the volumes observed in the natural history study. A weighted linear mixed-effects model showed a 54% reduction (P = .039).

The most common treatment emergent adverse reactions reported in the study were mucocutaneous events such as dry skin, lip dryness, alopecia, drug eruption, rash, and pruritus and musculoskeletal events such as arthralgia and premature growth plate closure in growing children.  While the drug appears to be well tolerated, it does come with a boxed warning. The drug is contraindicated in pregnancy due to the risk of teratogenicity and to minimize fetal exposure. The drug is to be administered only if conditions for pregnancy prevention are met. Also, the medication can cause premature epiphyseal closure in growing pediatric patients with FOP. Therefore, close monitoring is recommended in younger patients.

With the approval, the sponsor of the medication was given  a Rare Pediatric Disease Priority Review Voucher by the FDA. The voucher can be used for subsequent drug applications that would not qualify for a priority review. It can also be sold to another company. Recently, Sarepta Therapeutics sold their voucher for $102 million.

The manufacturers of the medication, Ipsen Pharmaceuticals, told Reuters that the estimated cost of the drug will be $624,000 per year (based on a 5 mg dose per day).

For patients 14 years and older, the recommended dosage is 5 mg once daily, with an increase in dose at the time of a flare-up to 20 mg once daily for 4 weeks, followed by 10 mg once daily for 8 weeks for a total of 12 weeks (20/10 mg flare-up treatment). For patients under 14 years, weight-adjusted for daily and flare-up dosing is recommended and clinicians should refer to the prescribing information for more details.

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Pignolo RJ et al. Reduction of new heterotopic ossification (HO) in the open-label, phase 3 MOVE trial of palovarotene for fibro dysplasia ossificans progressiva (FOP). J Bone Miner Res. 2023; 38: 381-394. doi:10.1002/jbmr.4762.