Upon issuance by the U.S. Patent and Trademark Office, Corcept plans to list the patent in the U.S. Food and Drug Administration’s Approved Drug Products with Therapeutic Equivalence Evaluations, known as the “Orange Book.” Korlym is currently protected by 10 patents listed in the Orange Book, which identifies FDA-approved products on the basis of safety and effectiveness.
The patent — 13/677,465 — is titled “Optimizing Mifepristone Absorption,” and will expire in November 2032. It is based on Corcept’s findings that the absorption of Korlym into the blood is increased when administered with meals. A dose ranging from 100 to 2,000 mg should be given within one hour of consuming a meal, increasing the therapy’s maximum plasma concentration compared with administration without food, the company says.
“This patent covers an important finding of our research — that for optimal effect, Korlym must be taken with food,” Joseph K. Belanoff, MD, Corcept’s CEO, said in a press release.
“Korlym’s label instructs doctors that ‘Korlym must always be taken with a meal,’” he added.
Another U.S. patent, PCT/US2018/020336, was issued to Corcept earlier this year, covering the use of Korlym in combination with strong CYP3A enzyme inhibitors to treat Cushing’s syndrome patients. That patent, “Concomitant Administration of Glucocorticoid Receptor Modulators and CYP3A Inhibitors,” will be in effect until 2037.
The antifungal medicine ketoconazole (trade name Nizoral) is able to strongly suppress CYP3A, which is key to breaking down Korlym into three active compounds.
Researchers discovered that treatment with ketoconazole increased the blood levels of Korlym metabolites, but did not impact the therapy’s effect in Cushing’s patients. That was seen with the reductions in blood levels of cortisol and ACTH, known as the adrenocorticotropic hormone.
While the two therapeutic agents can be safely combined, Korlym might need dose adjustments when used in combination with ketoconazole. The patent provides information on safe ways to do so.
Korlym was the first treatment approved in the U.S. for people with Cushing’s syndrome. It is a cortisol receptor blocker indicated for adults with high blood sugar caused by excess cortisol (hypercortisolism), who have type 2 diabetes or glucose intolerance, and have failed, or are not candidates for, surgical care.
Corcept focuses on finding and developing treatments for severe metabolic, oncologic, and psychiatric disorders by altering the effects of the steroid hormone cortisol.