FDA Approves Ipsen’s Sohonos for People with Fibrodysplasia Ossificans Progressiva

Rare Daily Staff

The U.S. Food and Drug Administration granted approval to Ipsen Pharma’s Sohonos capsules as a retinoid indicated for the reduction in volume of new bone formation in adults and pediatric patients aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva.

The approval comes four years after Ipsen paid $1 billion to acquire the drug’s developer Clementia Pharmaceuticals, several safety issues and clinical delays, and a rejection by the European Commission.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare bone disease that impacts the lives of an estimated 400 people in the U.S. and 900 people globally. As the disease continuously progresses with flare-up episodes causing rapid bone growth, HO severely restricts mobility and function. Most people living with FOP inevitably lose the ability to eat and drink on their own, cannot provide selfcare or use the restroom themselves, and are unable to maintain employment. By the age of 30 years old, the majority of people with FOP require a wheelchair and full-time caregiver assistance. The management of FOP has previously been limited to palliative care and ultimately, FOP shortens the median life expectancy to 56 years. Death is often caused by bone formation around the ribcage leading to breathing problems and cardiorespiratory failure or falls resulting in fractures or head injuries because joint ankylosis prevents bracing from a fall.

The FDA approval is based on the pivotal efficacy and safety data from the phase 3 MOVE trial, the first and largest multicenter, open-label trial in adult and pediatric patients. The 18-month data published in the Journal of Bone and Mineral Research, included 107 patients (12 percent of the estimated number of individuals worldwide living with FOP) who received oral palovarotene compared with untreated individuals from Ipsen’s global FOP Natural History Study. The study results demonstrated palovarotene effectively reduced annualized heterotopic ossification volume compared with no treatment beyond standard of care, (54 percent reduction with weighted linear mixed effect model). The study also demonstrated that palovarotene has a well-characterized safety profile, with adverse events consistent with the systemic retinoid class. 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.

“The FDA approval of Sohonos is a breakthrough for the U.S. fibrodysplasia ossificans progressiva community,” said Howard Mayer, head of Research and Development for Ipsen. “For the first time doctors have an approved medicine available to them, shown to reduce the formation of new, abnormal bone growth, known as heterotopic ossification (HO), which causes debilitating mobility challenges and has a devastating impact on the lives of people with FOP.”

Sohonos (palovarotene) is an oral medicine with particular selectivity for the gamma subtype of retinoic-acid receptors, which are an important regulator of skeletal development and ectopic bone in the retinoid signaling pathway. The medicine is designed to mediate the interactions between the receptors, growth factors and proteins within the retinoid signaling pathway to reduce new abnormal bone formation in FOP. The recommended dosing for Sohonos includes a chronic daily dosage of 5 mg (or weight-based equivalent for pediatric patients under 14 years of age), which can be modified/increased for flare-up symptoms. Sohonos may be prescribed immediately in the United States for eligible patients.

Sohonos received Orphan Drug and Breakthrough Therapy designations from the FDA for the treatment of FOP and was granted Priority Review of the New Drug application. Sohonos, under the generic name palovarotene, is also under review with a number of other regulatory authorities. In July 2023, the European Commission did not grant marketing authorization for palovarotene. Sohonos is currently authorized for use in eligible patients in United States, Canada, and with a conditional approval in the United Arab Emirates.

With this approval the FDA also issued a Rare Pediatric Disease Priority Review Voucher. The voucher can be used for subsequent drug applications that would not qualify for a priority review.

Photo: Howard Mayer, head of Research and Development for Ipsen