Clofutriben Receives FDA Orphan Drug Designation to Treat Endogenous Cushing Syndrome

The FDA granted orphan drug designation for clofutriben (Sparrow Pharmaceuticals), a potent and selective HSD-1 inhibitor, for the treatment of endogenous Cushing syndrome, also known as hypercortisolism. The company also announced the phase 2 RESCUE trial that assessed clofutriben among individuals with endogenous Cushing syndrome is complete, according to the release.¹

Image credit: Vitalii Vodolazskyi | stock.adobe.com

“We are pleased that the FDA has recognized the potential for clofutriben to treat this devastating disease,” Jamie MacPherson, PharmD, senior vice president of regulatory affairs and quality at Sparrow, said in a news release.¹

The rare endocrine disorder occurs when the body produces an excess of cortisol, caused by exposure to glucocorticoids, that are produced by the adrenal glands.² Symptoms for endogenous Cushing syndrome include weight gain, diabetes, hypertension, osteoporosis, muscle loss and weakness, fragile skin that bruises easily, stretch marks, depression, and cognitive changes.³ Study authors noted that the syndrome is often challenging to diagnose as it develops slowly and presents a wide range of symptoms in affected individuals.⁴

“HSD-1 inhibition with clofutriben is a completely novel approach to the treatment of endogenous Cushing syndrome that may overcome many of the serious problems with current therapies, including major safety, tolerability, and complexity issues such as the risk of adrenal insufficiency and adrenal crisis,” Frank Czerwiec, MD, PhD, chief medical officer at Sparrow, said in a news release.¹

Clofutriben could also offer further treatment for autonomous cortisol secretion, which is a milder and more dominant form of hypercortisolism than endogenous Cushing syndrome but remains a serious disease. As an HSD-1 inhibitor, its role as an intracellular enzyme is to activate glucocorticoids in target tissues, where cortisol as connected with morbidity including liver, adipose, brain, bone, muscle, and skin, according to study authors. Additionally, clofutriben in combination with the glucocorticoid medicine prednisolone is also being assessed in phase 2 clinical trials to treat immunological disorders.¹

The randomized, placebo-controlled RESCUE trial assessed clofutriben among individuals with ACTH-dependent endogenous Cushing syndrome, a form of the syndrome that occurs when body over produces adrenocorticotropic hormone.⁵ The study authors noted that rare disease is caused by a tumor that results in hypersecretion of cortisol.¹

“One of the most encouraging observations is that, given the option to continue clofutriben or switch to another treatment at the end of the trial, patients chose to continue clofutriben in the [open-label extension]. We are working closely with our medical, scientific, and patient advisors on plans to present these data and on designs for our next phase of clinical trials to startup next year,” said Czerwiec in a news release.¹

REFERENCES

1. Sparrow Pharmaceuticals Announces Completion of Phase 2 Trial and FDA Orphan Drug Designation of Clofutriben for Endogenous Cushing’s Syndrome. Sparrow Pharmaceuticals. News release. October 28, 2024. Accessed November 4, 2024. https://www.businesswire.com/news/home/20241028067997/en

2. Cushing Syndrome. StatPearls. June 26, 2023. Accessed November 4, 2024. https://www.ncbi.nlm.nih.gov/books/NBK470218/#:~:text=Endogenous%20Cushing%20syndrome%20results%20from,responsible%20for%20ACTH%2Ddependent%20Cushing.

3. Endogenous Cushing’s Syndrome. Sparrow Pharmaceuticals. Accessed November 4, 2024. https://sparrowpharma.com/endogenous-cushings-syndrome#:~:text=Cushing's%20can%20lead%20to%20a%20wide%20range,easily%2C%20stretch%20marks%2C%20depression%2C%20and%20cognitive%20changes.

4. Cushing’s Syndrome and Cushing Disease. Endocrine Society. January 24, 2022. Accessed November 4, 2024. https://www.endocrine.org/patient-engagement/endocrine-library/cushings-syndrome-and-cushing-disease#:~:text=Endogenous%20Cushing%20Syndrome:%20Endogenous%20Cushing,cortisol%20by%20the%20adrenal%20glands.

5. Guide to Cushing's Syndrome. Columbia Adrenal Center. October 2024. Accessed November 4, 2024. https://columbiasurgery.org/conditions-and-treatments/cushings-syndrome.