Treating Patients with Fibrodysplasia Ossificans Progressiva (FOP)

Mona Al Mukaddam, MD, Associate Professor of Clinical Medicine and Orthopaedic Surgery at Penn Medicine describes treatment options for persons with fibrodysplasia ossificans progressiva (FOP).

FOP is genetic disorder characterized by new bone formation outside of the normal skeletal system, a process known as heterotopic ossification. Heterotopic ossification, once formed, is irreversible and leads to loss of mobility and shortened life expectancy.

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

Until recently, the only treatment option for FOP was palliative in nature but a new treatment was recently approved that provides new options for these patients.

The newly approved treatment, 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).

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.