Abstract
Palovarotene (Sohonos™) is an orally bioavailable selective retinoic acid receptor (RAR)γ agonist being developed by Ipsen for the reduction of heterotopic ossification (HO) formation in patients with fibrodysplasia ossificans progressiva (FOP). By binding to RARγ, palovarotene inhibits bone morphogenetic protein and SMAD 1/5/8 signalling: interfering with these pathways prevents chondrogenesis and ultimately HO by permitting normal muscle tissue repair or regeneration to occur. Palovarotene received its first approval on 21 January 2022 to reduce the formation of HO in adults and children aged 8 years and above for females and 10 years and above for males with FOP in Canada. This article summarizes the milestones in the development of palovarotene leading to this first approval.
Similar content being viewed by others
References
Semler O, Rehberg M, Mehdiani N, et al. Current and emerging therapeutic options for the management of rare skeletal diseases. Paediatr Drugs. 2019;21(2):95–106.
Wentworth KL, Masharani U, Hsiao EC. Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva. Br J Clin Pharmacol. 2019;85(6):1180–7.
US National Library of Medicine. Genetics Home Reference: fibrodysplasia ossificans progressiva. 2021. https://medlineplus.gov/genetics/condition/fibrodysplasia-ossificans-progressiva/. Accessed 24 Feb 2022.
Pignolo RJ, Pacifici M. Retinoid agonists in the targeting of heterotopic ossification. Cells. 2021;10(11): 3245.
Ipsen Biopharmaceuticals Canada Inc. PrSOHONOSTM (palovarotene capsules 1 mg, 1.5 mg, 2.5 mg, 5 mg, 10 mg): Canadian product monograph. 2022. https://pdf.hres.ca/dpd_pm/00064435.PDF. Accessed 1 Feb 2022.
Health Canada. Notice of compliance information: SOHONOS. 2022. https://health-products.canada.ca/noc-ac/info.do?lang=en&no=27451. Accessed 22 Mar 2022.
Clementia Pharmaceuticals Inc. Clementia Pharmaceuticals Inc. announces closing of $22.5 million Series A financing with preeminent U.S. and Canadian healthcare venture capital funds [media release]. 10 Jan 2014. https://finance.yahoo.com/news/clementia-pharmaceuticals-inc-announces-closing-133000560.html.
Ipsen. Ipsen completes acquisition of Clementia Pharmaceuticals [media release]. 18 Apr 2019. https://www.ipsen.com/press-releases/ipsen-completes-acquisition-of-clementia-pharmaceuticals/.
Sinha S, Uchibe K, Usami Y, et al. Effectiveness and mode of action of a combination therapy for heterotopic ossification with a retinoid agonist and an anti-inflammatory agent. Bone. 2016;90:59–68.
Lees-Shepard JB, Nicholas SE, Stoessel SJ, et al. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity. Elife. 2018;7(e40814):1–20.
Pavey GJ, Qureshi AT, Tomasino AM, et al. Targeted stimulation of retinoic acid receptor-γ mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model. Bone. 2016;90:159–67.
Wheatley BM, Cilwa KE, Dey D, et al. Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat-related heterotopic ossification. J Orthop Res. 2018;36(4):1135–44.
Pignolo RJ, Al Mukaddam M, Baujat G, et al. Palovarotene (PVO) for fibrodysplasia ossificans progressiva (FOP): data from the phase III MOVE trial [abstract no. 1046]. J Bone Miner Res. 2020;35(Suppl 1):16–7.
US National Institutes of Health. ClinicalTrials.gov identifier NCT02279095. 2022. https://clinicaltrials.gov/. Accessed 1 Mar 2022.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The preparation of this review was not supported by any external funding.
Authorship and Conflict of interest
During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. S. M. Hoy is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.
Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability
Not applicable.
Additional information
This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Hoy, S.M. Palovarotene: First Approval. Drugs 82, 711–716 (2022). https://doi.org/10.1007/s40265-022-01709-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40265-022-01709-z