| Definition | Fibrodysplasia Ossificans Progressiva (FOP), with an estimated worldwide prevalence of one in 2 million individuals,[A244920] is an exceptionally rare genetic disorder. FOP is caused by a gain-of-function mutation in the ACVR1/ALK2 gene which results in progressive heterotopic ossification, a process wherein connective tissues (e.g. skeletal muscle, ligaments, tendons) are replaced with bone.[A244920] The ossification occurring as a result of FOP is insidious and cumulative, and is provoked during flare-ups or in response to injury. Treatment options for patients with FOP are extremely limited, although there has been substantial recent interest in novel treatments for this disease.[A244920]
Palovarotene is a selective agonist of retinoic acid receptor gamma (RARγ) belonging to a class of medications known as retinoids, similar in mechanism to drugs like [tazarotene] or [trifarotene], which are derivatives of [vitamin A]. It first garnered interest as a potential treatment for emphysema,[A3568,A3570] but was eventually recognized as a potential novel therapy for patients with FOP.[A244920] Agonists for retinoic acid receptors have been shown to inhibit chondrogenesis of heterotopic ossification in a transgenic mice model of FOP, with selective RARγ agonists (e.g. palovarotene) demonstrating the greatest efficacy.[A244920]
Palovarotene was approved for use in Canada in January 2022 for the management of heterotopic ossification in patients with FOP,[L39990] representing the first global approval for any FOP therapy.[L40020] It has been granted rare pediatric disease and breakthrough therapy designations from the US FDA, although a previously submitted NDA was withdrawn in August 2021 pending the resubmission of additional data analyses.[L40010] |
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