Palovarotene

In patients with FOP, abnormal bone formation, including heterotopic 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.

• SOHONOS is 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 a retinoid indicated for reduction in the volume of new heterotopic ossification in adults and children aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP) ( 1 ).

• SOHONOS is contraindicated in the following patients: During Pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . A history of allergy or hypersensitivity to retinoids, or to any component of SOHONOS.contraindicated

Obtain a negative pregnancy test in females of reproductive potential before initiation of SOHONOS ( 2.1 ) Recommended dosage includes a chronic daily dose, which can be increased for flare-up symptoms ( 2.2 ) 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) ( 2.2 ) For pediatric patients under 14 years: Weight-adjusted for daily and flare-up dosing. Recommended daily dosage range from 2.5 to 5 mg. Refer to Table 1 in Full Prescribing Information for complete pediatric dosing ( 2.2 ) Take SOHONOS with food preferably at same time each day ( 2.3 ). Reduce the dose in the event of adverse reactions as appropriate ( 2.4 ) See Full Prescribing Information for complete dosing instructions ( 2 ) 2.1 Pregnancy Testing Prior to Treatment with SOHONOS For females of reproductive potential, obtain a negative pregnancy test within one week prior to initiating and periodically during SOHONOS therapy . If pregnancy occurs, stop SOHONOS treatment immediately and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity. [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1 , 8.3) ]. 2.2 Recommended Dosage and Duration Dosage Overview Take SOHONOS with food preferably at the same time each day [see Dosage and Administration (2.3) ] .

Premature Epiphyseal Closure: Premature epiphyseal closure occurred with SOHONOS. Assess baseline skeletal maturity before SOHONOS therapy and monitor linear growth in growing pediatric patients ( 5.2 ) Mucocutaneous Adverse Reactions: Dry skin, lip dry, pruritus, rash, alopecia, erythema, skin exfoliation, and dry eye occurred with SOHONOS. Prevent or treat with skin emollients, sunscreen, artificial tears. Dosage reduction may be required in some patients ( 2.4 , 5.3 ) Metabolic Bone Disorders: Decreased vertebral bone mineral content and bone density may occur. Assess for spinal fracture periodically using radiologic method ( 5.4 ) Psychiatric Disorders: Depression, anxiety, mood alterations and suicidal thoughts and behaviors occurred with SOHONOS. Contact healthcare provider if new or worsening symptoms develop in patients treated with SOHONOS ( 5.5 ) Night Blindness: May occur and make driving at night hazardous ( 5.6 ) 5.1 Embryo-Fetal Toxicity SOHONOS can cause fetal harm and is contraindicated during pregnancy. SOHONOS is a member of the retinoid class of drugs which is associated with birth defects in humans. In animal reproduction studies, palovarotene administered orally to pregnant rats during organogenesis was teratogenic and caused fetal malformations typical of retinoids including cleft palate, misshapen skull bones, and shortening of the long bones at clinically relevant exposures.

The following clinically significant adverse reactions are described elsewhere in the labeling: Premature Epiphyseal Closure in Growing Pediatric Patients [see Warnings and Precautions (5.2) ] Mucocutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] Metabolic Bone Disorders [see Warnings and Precautions (5.4) ] Psychiatric Disorders [see Warnings and Precautions (5.5) ] Night Blindness [see Warnings and Precautions (5.6) ] Most common adverse reactions (incidence ≥10%) are dry skin, lip dry, arthralgia, pruritus, pain in extremity, rash, alopecia, erythema, headache, back pain, skin exfoliation, nausea, musculoskeletal pain, myalgia, dry eye, hypersensitivity, peripheral edema, and fatigue ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact IPSEN Biopharmaceuticals, Inc at 1-855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of SOHONOS was evaluated in clinical studies that enrolled a total of 164 subjects with FOP, including 139 subjects in the indicated population of ages 8 years and above for females and 10 years and above for males (8/10 years and older).

Pregnancy: May cause fetal harm ( 2.1 , 4 , 8.1 ) Growing pediatric patients are recommended to undergo baseline assessment of growth and skeletal maturity before starting treatment and continued clinical and radiographic monitoring every 6 to 12 months until patients reach skeletal maturity or final adult height ( 5.2 , 8.4 ) 8.1 Pregnancy Risk Summary SOHONOS is contraindicated during pregnancy. Based on the findings in animal studies and class effects of retinoids, SOHONOS can cause fetal harm when administered during pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ] . In animal reproduction studies, oral administration of palovarotene to pregnant rats during the period of organogenesis resulted in multiple fetal malformations typical of retinoids (e.g., cleft palate, malformed skull bone, shortening of the long bones) at doses ≥0.25 mg/kg/day (less than the clinical exposure) (see Data ) . There are no available human data on SOHONOS use in pregnant women. If pregnancy occurs during treatment with SOHONOS, discontinue treatment immediately and refer the patient to an obstetrician/gynecologist or other specialist experienced in reproductive toxicity for further evaluation and counseling.

Metabolism

Palovarotene exposure (AUC) increases proportionally from 0.02 to 50 mg (0.001 to 2.5 times the maximum recommended dosage). Steady-state is achieved by Day 3 following once daily dosing.

No clinical experience with an overdose of SOHONOS has been reported. SOHONOS is a derivative of vitamin A. In case of accidental overdose, signs of hypervitaminosis A could appear, including severe headache, nausea or vomiting, drowsiness, irritability and pruritus. Any overdose should be treated with supportive care according to the signs and symptoms exhibited by the patient.

• Aug 16, 2023NDANDA215559Ipsen

1. 1Condition Aggravated2854%
2. 2Dry Skin1019%
3. 3Product Dose Omission Issue917%
4. 4Pruritus917%
5. 5Skin Exfoliation917%
6. 6Off Label Use713%
7. 7Rash47.7%
8. 8Alopecia35.8%
9. 9Cross Sensitivity Reaction35.8%
10. 10Dyspepsia35.8%
11. 11Fall35.8%
12. 12Nausea35.8%
13. 13Dermatitis23.8%
14. 14Dermatitis Exfoliative Generalised23.8%
15. 15Ingrowing Nail23.8%

The 10 most recently updated of 12 ClinicalTrials.gov registrations naming Palovarotene as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Document and to Further Describe Long-term Safety and Effectiveness of Palovarotene in Participants With Fibrodysplasia Ossificans Progressiva (FOP)
  Recruiting · Observational · 100 enrolled · Ipsen
  NCT06089616updated 2026-05-28
• A Study of the Blood Levels of Palovarotene in Participants With Abnormal Liver Function Compared to Healthy Adult Participants After Intake of a Single Dose
  Completed · Phase 1 · Interventional · 31 enrolled · Ipsen
  NCT06908954updated 2026-04-30
• A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies.
  Completed · Phase 3 · Interventional · 61 enrolled · Ipsen
  NCT05027802updated 2025-06-22
• An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)
  Completed · Phase 2 · Interventional · 58 enrolled · Clementia Pharmaceuticals Inc.
  NCT02279095updated 2025-02-19
• An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.
  Completed · Phase 3 · Interventional · 107 enrolled · Clementia Pharmaceuticals Inc.
  NCT03312634updated 2023-11-29
• An Efficacy and Safety Study of Palovarotene for the Treatment of MO
  Terminated · Phase 2 · Interventional · 193 enrolled · Clementia Pharmaceuticals Inc.
  NCT03442985updated 2022-08-01
• Study to Compare the Pharmacokinetics, Safety, and Tolerability Following Administration of Palovarotene in Healthy Japanese and Non-Asian Subjects
  Completed · Phase 1 · Interventional · 18 enrolled · Clementia Pharmaceuticals Inc.
  NCT04829786updated 2021-04-02
• Study Evaluating the Effect of Food on the Pharmacokinetics of Palovarotene and the Effect of Palovarotene on the Pharmacokinetics of the CYP3A4 Substrate Midazolam in Two Cohorts of Healthy Adult Subjects
  Completed · Phase 1 · Interventional · 48 enrolled · Clementia Pharmaceuticals Inc.
  NCT04829773updated 2021-04-02
• Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Palovarotene Ophthalmic Solution in Healthy Adult Subjects
  Completed · Phase 1 · Interventional · 48 enrolled · Clementia Pharmaceuticals Inc.
  NCT04762355updated 2021-02-21
• An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects
  Completed · Phase 2 · Interventional · 40 enrolled · Clementia Pharmaceuticals Inc.
  NCT02190747updated 2021-02-16

Frequently asked questions

How does Palovarotene work?

In patients with FOP, abnormal bone formation, including heterotopic 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.

What is Palovarotene used for?

According to FDA labeling, Palovarotene carries indications including: SOHONOS is 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 a retinoid indicated for reduction in the volume of new heterotopic ossification in adults and children aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP) ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Palovarotene?

Palovarotene is classified as Other drugs for disorders of the musculo-skeletal system, Retinoid, Receptor Interactions.

What are the brand names for Palovarotene?

Palovarotene is marketed under brand names including Sohonos.

What are the contraindications for Palovarotene?

Palovarotene labeling lists contraindications including: SOHONOS is contraindicated in the following patients: During Pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . A history of allergy or hypersensitivity to retinoids, or to any component of SOHONOS.. Always consult the full prescribing information and a clinician.