Evidence Grade A — Regulatory approved. 61 published studies. 12 registered clinical trials.
Medically reviewed by a licensed medical professional
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Palovarotene (sold as Sohonos) is an oral medication for fibrodysplasia ossificans progressiva (FOP) — an extraordinarily rare genetic condition (approximately 1 in 1.3 million people) where the body's soft tissues progressively turn into bone, gradually encasing the skeleton in a second layer of bone that locks joints in place. It is the first and only treatment for FOP. Palovarotene is not a peptide.
Palovarotene is also known by these brand and alternate names:
61 published studies: 41 human, 9 animal, 8 in-vitro, 19 reviews
Palovarotene (Sohonos) is approved for FOP. The Phase III MOVE trial (107 patients — representing approximately 12% of the global FOP population) initially did not meet statistical significance on its pre-specified primary analysis. However, a post-hoc re-analysis with corrected placebo data showed a 54% reduction in new heterotopic ossification volume.
The approval pathway was complex given the ultra-rare nature of FOP. Palovarotene is not a peptide. Important safety considerations include premature growth plate closure in growing children, requiring monitoring. FOP has no other approved treatment.
Palovarotene selectively activates the retinoic acid receptor gamma, which blocks the aberrant bone-forming signalling pathway caused by the genetic mutation in FOP. By inhibiting this pathway, palovarotene reduces the abnormal bone formation that progressively restricts movement in FOP patients. The drug does not reverse existing heterotopic bone but aims to prevent new bone formation episodes.
FOP is so rare that fewer than 1,000 patients exist worldwide, making traditional clinical trials exceptionally challenging. The Phase III MOVE trial (107 patients — representing about 12% of the entire global FOP population) initially did not meet statistical significance on its planned primary analysis, but a corrected re-analysis showed a 54% reduction in new abnormal bone formation. The approval pathway has been uneven: the FDA approved it in August 2023 and Health Canada in January 2022, but the European Medicines Agency refused marketing authorisation in July 2023, citing insufficient evidence. Important safety concerns include premature growth plate closure in growing children (which could affect normal bone growth) and risk to unborn babies during pregnancy — both reflected in boxed warnings. As there is no other treatment for FOP, the risk-benefit calculation is different from conditions with existing alternatives.
PeptideTrace tracks 12 registered clinical trials for Palovarotene sourced from ClinicalTrials.gov.
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
A Study to Document and to Further Describe Long-term Safety and Effectiveness of Palovarotene in Participants With Fibrodysplasia Ossificans Progressiva (FOP)
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.
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
Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Palovarotene Ophthalmic Solution in Healthy Adult Subjects
Health Canada Market Authorisation
FDA ORIG 1
FDA SUPPL 2
Palovarotene (brand name Sohonos) is an oral retinoic acid receptor gamma (RARgamma) selective agonist. NOTE: This is a small molecule, NOT a peptide. Molecular weight 414.55 Da; molecular formula C27H30N2O2. CAS number: 410528-02-8. Developed by Ipsen, acquired through Clementia Pharmaceuticals. FDA approved August 16, 2023 for reduction of heterotopic ossification volume in adults and pediatric patients aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP). Health Canada approved January 2022. EMA refused marketing authorization in July 2023 citing insufficient evidence.
Palovarotene selectively agonizes RARgamma with approximately 10-fold greater affinity than RARalpha and RARbeta. This reduces BMP/ALK2 downstream signaling by inhibiting SMAD1/5/8 phosphorylation, blocking the aberrant endochondral bone formation (heterotopic ossification) driven by gain-of-function ACVR1/ALK2 mutations characteristic of FOP. The RARgamma selectivity minimizes retinoid-class effects mediated by other RAR subtypes.
The MOVE Phase 3 trial (N=107, representing approximately 12% of the global FOP population) used an episodic dosing regimen of 20 mg daily for 14 days followed by 10 mg daily for 28 days during flare-ups, with chronic dosing of 5 mg daily. The pre-specified primary analysis did not reach statistical significance; however, a post-hoc re-analysis confirmed by independent FDA review demonstrated a 54% reduction in annualized heterotopic ossification volume compared with natural history controls. The Endocrinologic and Metabolic Drugs Advisory Committee voted 11-3 in favor of approval. The label carries two boxed warnings: premature epiphyseal closure in growing children (growth plate fusion observed) and embryo-fetal toxicity (absolute contraindication in pregnancy).
This entry reflects historical nomenclature for the compound more commonly known as BPC-157. The evidence base, regulatory status, and limitations described for BPC-157 (#81) apply identically to this compound. See compound #81 for the full assessment. No marketing authorisation. No human Phase III trials. No established human dosing or safety profile.
BPC-157 has no marketing authorisation from any major regulatory agency. No human Phase III clinical trials have been completed. The preclinical evidence base consists of over 100 animal studies, predominantly conducted at the University of Zagreb. A small pilot study in ulcerative colitis (4 patients) has been reported but was uncontrolled. No established human dosing, safety profile, or efficacy data from rigorous clinical trials exist. Products available through unregulated channels are not subject to pharmaceutical manufacturing standards, and their composition, purity, and sterility cannot be assured. The gap between the extensive animal literature and the near-complete absence of human clinical data is the defining feature of this compound's evidence base.
Thymosin beta-4 has no current marketing authorisation. RegeneRx Biopharmaceuticals has conducted Phase II and Phase III trials of RGN-259 for dry eye disease and neurotrophic keratopathy, with mixed results. A Phase I cardiac study (RGN-352) demonstrated acceptable safety but did not advance to Phase II. Animal studies have consistently shown effects on wound healing and tissue repair. The clinical development programme has focused on ophthalmic applications. Thymosin beta-4 should be distinguished from the 7-amino-acid fragment TB-500 (#82), which is a different molecule with no independent clinical trial data.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
