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).
New bone formation outside of the normal skeletal system characterizes the genetic disorder FOP. This is caused by a process known as heterotopic ossification. Once formed, heterotopic ossification 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. However, 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.
Study/Trial
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
- 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.
To learn more about FOP and other genetic disorders, visit checkrare.com/diseases/congenital-and-genetic-conditions/
Reference
Pignolo RJ, Hsiao EC, Al Mukaddam M, 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.