Currently Enrolling Trials
Sohonos (palovarotene) is an orally bioavailable retinoic acid receptor agonist.
Sohonos is specifically indicated for the reduction in volume of new heterotopic ossification in adults and pediatric patients aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP).
- Sohonos is supplied as capsules for oral administraton.
- Obtain a negative pregnancy test in females of reproductive potential before initiation of Sohonos
- Recommended dosage includes a chronic daily dose, which can be increased for flare-up symptoms
- Take Sohonos with food preferably at same time each day
- Reduce the dose in the event of adverse reactions as appropriate
For adults and pediatric patients 14 years and older: Recommended dosage is 5 mg once daily, with an increase in dose at the time of a flare-up to 20 mg once daily for 4 weeks, followed by 10 mg once daily for 8 weeks for a total of 12 weeks (20/10 mg flare-up treatment)
For pediatric patients under 14 years: Weight-adjusted for daily and flare-up dosing. Recommended daily dosage range from 2.5 to 5 mg. See drug label for dose adjustments.
Mechanism of Action
In patients with FOP, abnormal bone formation, including heterotrophic ossification (HO), is driven by a gain-of-function mutation in the bone morphogenetic protein (BMP) type I receptor ALK2 (ACVR1). Palovarotene is an orally bioavailable retinoic acid receptor agonist, with particular selectivity at the gamma subtype of RAR. Through binding to RARγ, palovarotene decreases the BMP/ALK2 downstream signaling pathway by inhibiting the phosphorylation of SMAD1/5/8, which reduces ALK2/SMAD-dependent chondrogenesis and osteocyte differentiation resulting in reduced endochondral bone formation.
Adverse effects associated with the use of Sohonos may include, but are not limited to, the following:
- dry skin and lips
- pain in extremity
- back pain
- skin exfoliation
- musculoskeletal pain
- dry eye
- peripheral edema
The Sohonos drug label comes with the following Black Box warning: Sohonos is contraindicated in pregnancy. Because of the risk of teratogenicity and to minimize fetal exposure, Sohonos is to be administered only if conditions for pregnancy prevention are met. Sohonos causes premature epiphyseal closure in growing pediatric patients with FOP, close monitoring is recommended.
Clinical Trial Results
The FDA approval of Sohonos 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 18-month data 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% reduction with weighted linear mixed effect model).