On Aug. 16, 2023, the U.S. Food and Drug Administration (FDA) granted approval to the company Ipsen for their therapy for fibrodysplasia ossificans progressiva (FOP). The new drug, called Sohonos™ (palovarotene) capsules, is the first treatment for patients living with the ultra-rare connective tissue disorder, which affects only about 400 people in the U.S. and 900 people globally. The disease is characterized by abnormal bone formation outside of the normal skeletal system (heterotopic ossification; HO). The recommended daily dose of Sohonos is 5mg for adults and it is weight-based for pediatric patients under 14 years old. The recommended dosage for female patients aged 8 years to 13 years and males aged 10 years to 13 years is weight-based ranging from 2.5 mg to 5 mg daily. Dosing may be modified for flare-ups. It was launched upon approval with unknown access or network at this time. At a 5mg daily dose, the cost is $624,000 per year. For full prescribing information see here.
At a Glance
- Brand (Generic) Name: Sohonos (palovarotene) capsules
- Manufacturer: Ipsen
- Date Approved: Aug. 16, 2023
- Indication: for the reduction in the volume of new HO caused by FOP in adults and pediatric patients aged eight years and older for females and 10 years and older for males
- Dosage Forms Available: 1mg, 1.5mg, 2.5mg, 5mg, and10 mg oral capsules
- Launch Date: Immediately
- Estimated Annual Cost: $624,000 per year for the adult dose for the average list price
- Heterotopic ossification (HO), which occurs in ligaments, tendons, and skeletal muscle, can be preceded by painful soft-tissue swelling or “flare-ups.” In FOP, flare-up episodes are common and are a substantial contributor to the formation of new HO; however, HO can form in the absence of a flare-up. Once formed, HO is irreversible, leads to loss of mobility, and shortens life expectancy to about 56 years.
- FOP typically presents itself early in childhood and progresses during a patient’s lifetime. Most patients will have malformations of the thumbs and big toes early on. Patients eventually have difficulty moving — with joints locking up as their soft tissue essentially transforms into bone. If the jaw is involved, patients may have trouble eating or speaking.
- Currently, patients who have FOP are treated with high doses of corticosteroids for flare-ups and non-steroidal anti-inflammatory drugs (NSAIDs) in between flare-ups.
- Sohonos is a retinoic acid receptor gamma (RARγ) selective agonist expressed on immature cartilage tissue. It helps prevent bone morphogenetic protein (BMP) and maintains retinoid signaling which prevents bone growth signaling.
- Approval was based on the phase III pivotal trial, MOVE. The trial included 107 patients from around the globe who received treatment. Their disease progression then was compared to the progression of untreated individuals in the sponsor’s global FOP Natural History Study. Results showed a 54% reduction in annualized HO volume for those who were treated vs. untreated individuals.
- The most common adverse events (AEs) were dry skin, dry lips, alopecia, drug eruption, rash, itching, arthralgia, and premature closure of physes (pediatric growth plates).
- Sohonos has a boxed warning for the risk of embryo-fetal toxicity and premature epiphyseal closure in growing pediatric patients.
- The approval was granted under Priority Review, Orphan Drug Designation, and as a Breakthrough Therapy. Upon approval, Ipsen was granted an FDA Rare Pediatric Disease Priority Review Voucher that can be used on a future application or sold to another company.