Endocrine Society: Court reversal of mifepristone approval ‘alarming’

Mifepristone is active ingredient in Korlym, used for hard to treat Cushing's syndrome

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by Steve Bryson, PhD |

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A federal court ruling in Texas that reversed the U.S. Food and Drug Administration’s (FDA) 23-year-old approval of mifepristone has been met with deep concern by the Endocrine Society.

Mifepristone, the active ingredient in Mifeprex, is used to end a pregnancy. It’s also the active ingredient of Korlym, a therapy approved by the FDA in 2012 to lower high blood sugar levels in adults with hard to treat Cushing’s syndrome who have type 2 diabetes or glucose intolerance.

The court overturned the 2000 approval of mifepristone for medical abortions, accepting the argument it wasn’t safe. While the ruling judge paused his decision for a week, allowing time for the government to appeal, the ban calls into question the FDA’s authority to regulate medications.

“We believe the FDA, not the court, should have the authority to approve drugs and determine their efficacy and safety based on medical evidence and established standards and processes,” Ursula Kaiser, MD, president of the Endocrine Society, said in a press release.

Complicating matters, in a separate case, a federal court in Washington blocked the FDA from making any changes by certain states to reduce the availability of the medicine, which leaves “access to mifepristone unclear for both the treatment of Cushing’s syndrome and for medical abortions,” the Endocrine Society maintains.

Cushing’s syndrome is a group of diseases marked by excess levels of cortisol, a glucocorticoid hormone made by the adrenal glands that helps control a broad range of bodily functions, including blood sugar (glucose) levels. Too much cortisol can cause blood sugar levels to rise, a hallmark of type 2 diabetes and glucose intolerance.

Cushing’s disease is a form of Cushing’s syndrome mainly caused by noncancerous tumors in the pituitary gland. that stimulate the over-production of adrenocorticotropic hormone (ACTH). This triggers the adrenal glands to produce and release too much cortisol.

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Phase 4 trial to assess if high cortisol levels common with type 2 diabetes

The use of mifepristone for treating Cushing’s syndrome

Surgically removing the pituitary tumors is the treatment of choice for Cushing’s patients, but for some, surgery isn’t an option or has failed to control their symptoms.

Korlym, developed and marketed by Corcept Therapeutics, is approved to reduce high blood sugar levels in these hard-to-treat cases. It works by binding to glucocorticoid receptors on the surface of cells, effectively preventing cortisol from interacting with them and triggering the cascade of events leading to high blood sugar levels and diabetes.

Its approval was supported by data from a Phase 3 trial (NCT00569582), which enrolled 50 adults with Cushing’s syndrome and type 2 diabetes or glucose intolerance, or high blood pressure alone.

Korlym led to a clinically meaningful improvement in glucose control in 60% of those with diabetes and lowered blood pressure in 38% with high blood pressure.

An independent data review board, which assessed a range of symptoms, including body composition and weight, Cushing-like appearance, and psychological symptoms, reported that overall clinical improvement was seen in 87% of participants.

Common side effects included fatigue, headache, low potassium levels, joint pain, nausea, vomiting, and swelling.

A Phase 4 trial (NCT01990560), conducted post-approval in a real-world setting, indicated Korlym might help manage mild autonomous cortisol secretion (ACS), an asymptomatic form of Cushing’s syndrome. The treatment reduced fasting glucose levels and insulin resistance, which occurs when cells fail to adequately respond to insulin.

Another study suggested Korlym can effectively treat patients with ectopic Cushing’s syndrome caused by tumors outside the pituitary gland.

Mifepristone is being investigated for treating cancers affecting the lung, prostate, breast, and ovaries, as well as for alcohol use disorder.

“Physicians and trained health professionals should be able to make medical decisions based on science and the circumstances of the individual patient rather than politics,” the Endocrine Society stated.