FDA Okays First-Ever New Drug for Rare Bone Disorder

Miriam E. Tucker

August 17, 2023

The US Food and Drug Administration (FDA) has approved palovarotene (Sohonos), the first-ever treatment for people with the rare and severely disabling bone condition fibrodysplasia ossificans progressiva (FOP).

Affecting roughly 400 people in the United States and 900 worldwide, FOP is an autosomal dominant condition in which bone develops in soft connective tissue areas of the body where it isn't normally present (heterotopic ossification), such as the ligaments, tendons, and skeletal muscles. This leads to severe restriction in mobility and function, to the point that people lose the ability to feed or care for themselves. Most are completely disabled by age 30 years and median life expectancy is 56 years, with death often due to bone formation around the rib cage restricting respiration.

"As a clinician caring for patients with FOP, I personally see the daily challenges and stresses that our patients and their families must contend with…since the accumulation of heterotopic ossification in FOP is progressive, irreversible, and life altering. This medication is an important treatment option for our FOP community," said endocrinologist Edward Hsiao, MD, professor of medicine at the University of California, San Francisco, in a statement from Ipsen.

Taken orally, palovarotene selectively targets the gamma subtype of retinoic acid receptors that regulate skeletal development and ectopic bone in the retinoid signaling pathway. The drug mediates interactions between these receptors, growth factors, and proteins within that pathway to reduce new abnormal bone formation.

It is now FDA-approved for the treatment of FOP in female patients aged 8 years or older and male patients aged 10 years or older. The recommended dosing is 5 mg daily or weight-based equivalent for pediatric patients under 14 years of age, which can be modified or increased for flare-up symptoms. It is contraindicated during pregnancy.

The FDA approval was based on 18-month data from the phase 3 multicenter, open-label MOVE trial that included 107 adult and pediatric patients, over 10% of the world's population with FOP. All received oral palovarotene and were compared with untreated individuals from a prior natural history study of the condition. The drug reduced annualized heterotopic ossification volume by 54%.

Side effects were typical of those seen with other systemic retinoid drugs, including mucocutaneous events such as dryness of the skin and mucous membranes, alopecia, drug eruption, rash, and pruritus, and musculoskeletal events, such as arthralgia and premature growth plate closure in growing children.

According to Hsiao, who was a MOVE investigator, the study "showed that Sohonos can decrease new heterotopic ossification, and that palovarotene can be tolerated by many patients with FOP. Sohonos is not for everyone. As with all medicines there are risks in this case especially for young children who may develop early growth plate closure. In addition, Sohonos has the same side effects as other retinoids."

The FDA approval of palovarotene follows its rejection for marketing authorization in the European Union in July 2023.

Reached for comment, an Ipsen spokesperson told Medscape Medical News, "We reached the end of the regulatory process in the European Union for Sohonos and are disappointed the European Commission decided not to approved palovarotene for people with FOP in Europe."

The company is developing another drug, fidrisertib, for treating FOP. A pivotal phase 2 trial for that drug is now recruiting patients. Asked where Ipsen might try to market fidrisertib, the spokesperson replied, "At this point, our focus is on the completion of the pivotal trial."

Meanwhile, in the US, the FOP community is celebrating the palovarotene approval. In a statement, Michelle Davis, executive director of the International Fibrodysplasia Ossificans Progressiva Association, said, "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…The first treatment for FOP has been proven to reduce the volume of new abnormal bone growth, which may result in better health outcomes for people living with FOP."

Ipsen is offering a patient support program to assist with education, coverage, and reimbursement (1-866-435-5677).

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker

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