FDA Approves Palovarotene for Fibrodysplasia Ossificans Progressiva

US Food and Drug Administration (FDA)

The US Food and Drug Administration (FDA) has approved palovarotene capsules (Sohonos) as the first-and-only treatment for people living with fibrodysplasia ossificans progressiva (FOP).¹

Ipsen announced the approval of the palovarotene capsules as a retinoid indicated for reducing the volume of new heterotopic ossification in adults and pediatric patients aged 8 years and older for females and 10 years and older for males living with FOP.

“The FDA approval of Sohonos is a breakthrough for the US FOP community,” Howard Mayer, head of research and development at Ipsen, said in a statement. “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, which causes debilitating mobility challenges and has a devastating impact on the lives of people with FOP.”

An estimated 400 people in the US and 900 people worldwide are impacted by FOP. The disease continually progresses with flare-up episodes leading to rapid heterotopic ossification, severely restricting mobility, and function. Most people living with FOP lose the ability to eat and drink on their own, cannot provide self-care or use the bathroom alone, and are unable to maintain employment.²

Palovarotene is an oral medicine with particular selectivity for the gamma subtype of retinoic-acid receptors, an important regulator of skeletal development and ectopic bone in the retinoid signaling pathway. The therapy is designed to mediate the interaction between the receptors, growth factors, and proteins within the retinoid signaling pathway to reduce abnormal bone formation in FOP.

The FDA approval was based on 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 trial included 107 patients, or 12% of the estimated number of people with FOP worldwide, who received oral palovarotene compared with untreated individuals from the global FOP Natural History Study.

Eighteen-month study results showed palovarotene reduced annualized heterotopic ossification volume compared with no treatment beyond standard of care by 54% in a weighted linear mixed-effect mode. Results also indicated the well-characterized safety profile of palovarotene, with consistent adverse events to the systemic retinoid class.

Safety data showed the most common treatment-emergent adverse reactions in the study were mucocutaneous events, including dry skin, lip dryness, alopecia, drug eruption, rash, pruritus, and musculoskeletal events, such as arthralgia and premature growth plate closure in growing children.

Palovarotene can be prescribed immediately in the U.S. for eligible patients. Dosing recommendations for palovarotene capsules include a chronic daily dosage of 5 mg, or weight-based equivalent for pediatric patients under 14 years of age and can be modified or increased for flare-up symptoms.

Management of FOP has previously been limited to palliative care, as FOP shortens the median life expectancy to 56 years. Untimely death has been linked to bone formation around the ribcage leading to breathing problems and cardiorespiratory failure, as well as fractures or head injuries when joint ankylosis prevents patients from bracing for a fall.

“FOP is life-altering to the individuals diagnosed and their families,” Michelle David, executive director of the International FOP Association, said in a statement. “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 previously received a Complete Response Letter from the FDA in December 2022, related to the regulatory agency’s previous request for additional information on palovarotene clinical trial data.³

References

1. US FDA approves Ipsen’s sohonosTM (palovarotene) capsules, the first and only treatment for people with fibrodysplasia ossificans progressiva. United States. August 17, 2023. Accessed August 17, 2023. https://www.ipsen.com/us/press-releases/us-fda-approves-ipsens-sohonostm-palovarotene-capsules-the-first-and-only-treatment-for-people-with-fibrodysplasia-ossificans-progressiva/.
2. Fibrodysplasia ossificans progressiva - symptoms, causes, treatment: Nord. National Organization for Rare Disorders. January 12, 2023. Accessed August 17, 2023. https://rarediseases.org/rare-diseases/fibrodysplasia-ossificans-progressiva/.
3. Ipsen receives complete response letter for Palovarotene, an investigational treatment for fibrodysplasia ossificans progressiva. United States. June 26, 2023. Accessed August 17, 2023. https://www.ipsen.com/us/press-releases/ipsen-receives-complete-response-letter-for-palovarotene-an-investigational-treatment-for-fibrodysplasia-ossificans-progressiva/.