Sohonos Approved for Fibrodysplasia Ossificans Progressiva

The Food and Drug Administration (FDA) has approved Sohonos^™ (palovarotene) for reduction in the volume of new heterotopic ossification (HO) in adults and children aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by an abnormal development of bone in areas outside the normal skeleton. The disease causes restricted movement and fused joints, leading to deformities, restricted mobility and premature mortality. Palovarotene reduces new abnormal bone formation by selectively targeting the retinoic-acid receptor gamma (RARγ) within the retinoid signaling pathway.

The approval was based on data from the phase 3 MOVE trial (ClinicaTrials.gov Identifier: NCT03312634), an open-label study that enrolled patients with FOP with R206H mutation aged 4 years and older. Patients (N=97) received oral palovarotene 5mg once daily, increased at the time of flare-up symptoms to 20mg once daily for 4 weeks, followed by 10mg once daily for 8 weeks (chronic/flare-up regimen), with flare-up treatment extension in 4-week increments for persistent symptoms. The 12-week treatment restarted if the patient had another flare-up or substantial high-risk traumatic event anytime during flare-up treatment.

The primary endpoint was annualized change in new HO volume measured by low-dose whole-body computed tomography. Efficacy data were compared with data from FOP Natural History Study (NHS) participants (untreated beyond standard of care; ClinicalTrials.gov Identifier: NCT02322255).

Based on a linear mixed effect model, mean annualized new HO was reported to be 9.4 cm³/year in patients receiving the chronic/flare-up palovarotene treatment and 20.3 cm³/year in untreated patients in the NHS. The treatment effect was about 10.9 cm³/year (95% CI, -21.2, -0.6).

The most common adverse reactions reported with treatment were dry skin, lip dry, arthralgia, pruritis, pain in extremity, rash, alopecia, erythema, headache, back pain, skin exfoliation, nausea, musculoskeletal pain, myalgia, dry eye, hypersensitivity, peripheral edema, and fatigue.

The prescribing information for Sohonos includes a Boxed Warning regarding the risk of embryo-fetal toxicity and premature epiphyseal closure in growing pediatric patients with FOP. Sohonos is contraindicated in pregnancy because of the risk of teratogenicity. A negative pregnancy test should be obtained prior to initiating therapy.

Sohonos is supplied in 1mg, 1.5mg, 2.5mg, 5mg and 10mg capsules. Ipsen has launched a patient support program to ensure access to Sohonos for eligible individuals (1-866-435-5677). The product is now available for prescribing.