Palovarotene in fibrodysplasia ossificans progressiva: review and perspective

  • Vincent A. Verheij
  • , Robert J. Diecidue
  • , Esmée Botman
  • , Joseph D. Harrington
  • , Nobuhiko Haga
  • , Alberto Hidalgo-Bravo
  • , Patricia L. R. Delai
  • , Vrisha Madhuri
  • , Mona Al Mukaddam
  • , Keqin Zhang
  • , Tae-Joon Cho
  • , Rolf Morhart
  • , Richard Keen
  • , Carmen L. de Cunto
  • , Clive S. Friedman
  • , Zvi Grunwald
  • , Michael Zasloff
  • , J. Coen Netelenbos
  • , Edward Hsiao
  • , Frederick S. Kaplan
  • Robert J. Pignolo, Christiaan Scott, Elisabeth Marelise W. Eekhoff*
*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

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Abstract

Introduction: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.A., Canada and Australia but remains unapproved in Europe where concerns surrounding the drug and its path to regional market authorization persist. Areas covered: The developmental history of palovarotene and an overview of the clinical trials and the regulatory approval journey are discussed by global FOP experts. Expert opinion: While post hoc analyses indicate that palovarotene may have modest benefits for the inhibition of new HO formation in FOP, a number of limitations and concerns remain about its generalized use. Although the long-term risks and benefits of treatment with palovarotene remain unknown, the regional approval of palovarotene marks a milestone for the FOP community at the very beginning of a new era of clinical trials.
Original languageEnglish
Pages (from-to)291-299
Number of pages9
JournalExpert opinion on pharmacotherapy
Volume26
Issue number3
DOIs
Publication statusPublished - 2025

Keywords

  • Palovarotene
  • fibrodysplasia ossificans progressive
  • heterotopic ossification
  • outcome treatment trials
  • retinoic acid receptor gamma agonist
  • review

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