Medication Summary

Palovarotene was the first drug approved for fibrodysplasia ossificans progressiva (FOP).^[38] Clinical trials have been underway with fidresertib, saractinib, garetosmab (REGN 2477), and rapamycin.^{[47, 48]}

Class Summary

In patients with fibrodysplasia ossificans progressiva, abnormal bone formation, including heterotrophic ossification, is driven by a gain-of-function mutation in the bone morphogenetic protein (BMP) type I receptor ALK2 (ACVR1). By binding to RARγ, palovarotene decreases the BMP/ALK2 downstream signaling pathway by inhibiting phosphorylation of SMAD1/5/8, which reduces ALK2/SMAD-dependent chondrogenesis and osteocyte differentiation resulting in reduced endochondral bone formation.

Palovarotene (Sohonos)

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Indicated for reduction in volume of new heterotopic ossification in adults and pediatric patients aged ≥8 years for females and ≥10 years for males with fibrodysplasia ossificans progressiva (FOP).

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Media Gallery

Widespread tumors and indurations mainly in the scapular area, found on radiographic examination to consist of heterotopic bone formation.
Typical hallus valgus deformity.
Proliferation of fibroblasts within the muscle with partial replacement of the muscle fibers.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Slawomir Majewski, MD Professor and Director, Department of Dermatology and Venereology, Warsaw School of Medicine, Poland

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jean Paul Ortonne, MD Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France

Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Sebastian S Majewski †

Disclosure: Nothing to disclose.

Stefania Jablonska, MD † Former Chairman, Professor Emeritus, Department of Dermatology, Warsaw School of Medicine, Poland

Disclosure: Nothing to disclose.