An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.

Summary

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO) often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to ankyloses of major joints with cumulative and irreversible loss of movement and disability.

Timeline

Start

2017-11-30

Primary completion

2020-01-24

Completion

2022-09-07

Outcome

Sources disagree · no verdict is set; each source's reading is shown below

release “Dosing of palovarotene in the MOVE clinical trial was paused when futility criteria were met at a pre-specified interim analysis.” reads as missed primary endpoint ipsen.com ↗

release “Advisory committee voted 10 for and 4 against that evidence from the Phase III MOVE study show palovarotene is an effective treatment” reads as met primary endpoint ipsen.com ↗

release “Post hoc analyses* of the primary endpoint from the trial demonstrated a 62% reduction in mean annualized new HO volume” reads as met primary endpoint ipsen.com ↗

release “The published Phase III MOVE study showed that Sohonos can decrease new heterotopic ossification” reads as met primary endpoint ipsen.com ↗

Publications

• Background Shimono K, Tung WE, Macolino C, Chi AH, Didizian JH, Mundy C, Chandraratna RA, Mishina Y, Enomoto-Iwamoto M, Pacifici M, Iwamoto M. Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-gamma agonists. Nat Med. 2011 Apr;17(4):454-60. doi: 10.1038/nm.2334. Epub 2011 Apr 3.
• Lindborg CM, Al Mukaddam M, Baujat G, Cho TJ, De Cunto CL, Delai PLR, Eekhoff EMW, Haga N, Hsiao EC, Morhart R, de Ruiter R, Scott C, Seemann P, Szczepanek M, Tabarkiewicz J, Pignolo RJ, Kaplan FS. Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility. Clin Orthop Relat Res. 2023 Dec 1;481(12):2447-2458. doi: 10.1097/CORR.0000000000002672. Epub 2023 May 8.
• Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Brown MA, Cheung AM, De Cunto C, Delai P, Haga N, Kannu P, Keen R, Le Quan Sang KH, Mancilla EE, Marino R, Strahs A, Kaplan FS. Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP). J Bone Miner Res. 2023 Mar;38(3):381-394. doi: 10.1002/jbmr.4762. Epub 2023 Jan 25.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Palovarotene	Small molecule	5 mg	Oral
Subject	Palovarotene	Small molecule	10 mg	Oral

Indications