Palovarotene, sold under the brand name Sohonos, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used for the treatment of

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

and

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

. It is a highly selective retinoic acid receptor gamma (RARγ)

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

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

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 respo ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

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 Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designations by the United States

(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 pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) in 2014. Phase II 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 progressiva 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 drug development and commercialization in three therapeutic areas: oncology, rare diseases and neuroscience. Ipsen is one of the world's top 15 biopha ...

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

{{Authority control Retinoids Pyrazoles Benzoic acids Tetralins Orphan drugs