FDA Approves First Drug for Rare Bone Disorder

The FDA has approved Sohonos (palovarotene) to reduce new abnormal bone formation in people living with fibrodysplasia ossificans progressiva (FOP), an ultra-rare genetic disease that transforms the body’s soft issue into bone. Sohonos is indicated to treat girls 8 years of age and older and boys 10 years of age or older.

FOP impacts less than an estimated 400 people in the United States and 900 people globally. By the age of 30 years old, the majority of people with FOP require a wheelchair and full-time caregiver assistance. Life expectancy is about 56 years, and the management of FOP has previously been limited to palliative care

Developed by Ipsen, Sohonos targets the gamma subtype of retinoic-acid receptors, which are important regulators of skeletal development. It is designed to mediate the interactions between the receptors, growth factors and proteins within the retinoid signaling pathway to reduce new abnormal bone formation.

Sohonos is now available. The annual list price is $624,000 based for 5 mg dose per day, which a spokesperson for Ipsen told Formulary Watch is based on the value that medicine provides, including clinical benefit, economic value, social and quality of life measures, prevalence of the condition and if treatment options are available. She said the price may vary because the treatment is variable for pediatric patients based on weight and dose-increases for flare-up episodes.

Ipsen is providing personalized support, financial and insurance assistance programs to assist patients and their families. The spokesperson said the company is in conversations with all major health insurers, including the U.S. government, to discuss Sohonos and FOP.

“FOP is life-altering to the individuals diagnosed and their families. There’s not a day that goes by where those impacted don’t worry about the debilitating physical pain of muscle that is replaced by bone, another joint locking or the relentless emotional toll of losing the ability to do an activity they love, or hold a loved one close,” Michelle Davis, executive director of International FOP Association, said in a press release.

The approval is based on data from phase 3 MOVE trial. The 18-month data published in the Journal of Bone and Mineral Research, included 107 patients who received oral Sohonos compared with untreated individuals from Ipsen’s global FOP Natural History Study. In the study, Sohonos reduced annualized heterotopic ossification volume compared with no treatment beyond standard of care.

The most common treatment emergent adverse reactions were dry skin, lip dryness, alopecia, drug eruption, rash, and pruritus and musculoskeletal events such as arthralgia and premature growth plate closure in growing children. Sohonos label includes a boxed warning about the risk of premature plate closure, as well as the risk of fetal harm in pregnant women.

The approval follows an FDA advisory committee meeting in June 2023 in which members of the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) voted 11 to 3 in favor of the benefits of Sohonos outweigh the risks.

“Despite the risks of premature visual closure and potential increases in flare ups and vertebrae fractures, the potential benefits of the study drug to reduce new heterotopic ossification outweigh those risks,” Committee Chairpesons Cecilia C. Low Wang, M.D., professor of Medicine, University of Colorado, said after the vote. “I felt the open public hearing comments for incredibly compelling. We really have no other alternatives that might alter this disease course. But this drug might.”