Palovarotene, sold under the brand name Sohonos, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

used for the treatment of

heterotopic ossification Heterotopic ossification (HO) is the process by which bone tissue forms outside of the skeleton in muscles and soft tissue. Symptoms In traumatic heterotopic ossification (traumatic myositis ossificans), the patient may complain of a warm, tend ...

and

fibrodysplasia ossificans progressiva Fibrodysplasia ossificans progressiva (; FOP; also called Münchmeyer disease and formerly called myositis ossificans progressiva or Stoneman disease) is an extremely rare connective tissue disease in which fibrous connective tissue such as mus ...

. It is a highly selective

retinoic acid receptor gamma Retinoic acid receptor gamma (RAR-γ), also known as NR1B3 (nuclear receptor subfamily 1, group B, member 3) is a nuclear receptor encoded by the ''RARG'' gene. Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor ...

(RARγ)

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

. It was approved for medical use in Canada in June 2022, and in the United States in August 2023.

Medical uses

Palovarotene is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of heterotopic ossification and fibrodysplasia ossificans progressiva.

History

Palovarotene is a retinoic acid receptor gamma (RARγ) agonist licensed to Clementia Pharmaceuticals from Roche Pharmaceuticals. At Roche, palovarotene was evaluated in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). A one-year trial did not demonstrate a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α(1)-antitrypsin deficiency. In 2011, animal studies demonstrated that RARγ agonists, including palovarotene, blocked new bone formation in both an injury-induced mouse model of heterotopic ossification (HO) and a genetically modified biological mouse model of fibrodysplasia ossificans progressiva containing a continuously active ACVR1/ALK2 receptor in a dose-dependent manner. A 2016 study demonstrated that palovarotene also inhibited spontaneous heterotopic ossification, maintained limb mobility and functioning, and restored skeletal growth in fibrodysplasia ossificans progressiva mouse models.

Society and culture

Legal status

Palovarotene is being developed by Ipsen Biopharmaceuticals and was granted priority review and

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designations by the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) for the treatment of fibrodysplasia ossificans progressiva and orphan medicinal product designation by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) in 2014.

Phase II Phase II, Phase 2 or Phase Two may refer to: Media * Marvel Cinematic Universe: Phase Two, six American superhero films from 2013–2015 * ''Star Trek: Phase II'', an unrealized television series based on the characters of Gene Roddenberry's ''S ...

clinical studies failed to show a significant change in heterotopic bone volume, the main outcome measure, but prompted further investigation in a phase III clinical trial. In December 2022, the FDA declined to approve palovarotene for the fibrodysplasia ossificans progressive without additional clinical trial data. In January 2023, the

(EMA) recommended the refusal of the marketing authorization for palovarotene for the treatment of fibrodysplasia ossificans progressiva. In May 2023, the European Medicines Agency confirmed its recommendation to refuse marketing authorization for Sohonos.

Research

Phase II

Clementia submitted a new drug application for palovarotene for the treatment of fibrodysplasia ossificans progressiva after observing positive phase II results.

Phase III

In December 2019,

Ipsen Ipsen is a French biopharmaceutical company headquartered in Paris, France, with a focus on transformative medicines in three therapeutic areas: oncology, rare disease and neuroscience. Ipsen is one of the world’s top 15 biopharmaceutical com ...

issued a partial clinical hold for people under the age of 14, due to reports of early fusion of growth plates. Ipsen acquired Clementia in 2019.

References

External links

Retinoids Pyrazoles Benzoic acids Tetralins Orphan drugs {{musculoskeletal-system-drug-stub