Relacorilant, an investigational therapy developed by Corcept Therapeutics, may effectively manage the effects of excess cortisol in patients with Cushing’s syndrome, interim data from an ongoing Phase 2 trial show.
In particular, the treatment significantly improved sugar tolerance and the levels of osteocalcin, a bone growth biomarker commonly suppressed by excess cortisol.
Corcept announced in a press release that the trial (NCT02804750) has completed patient enrollment. Results from the first patients will be presented during the upcoming 27th American Association of Clinical Endocrinologists (AACE) annual meeting, May 16-20 in Boston. Full data is expected by the third quarter of 2018.
Relacorilant, also known as CORT125134, was designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor.
In a Phase 1 trial with healthy volunteers, multiple doses of relacorilant had a similar effect as Korlym (mifepristone) — an approved medicine for Cushing’s patients — without its known side effects.
In addition to the early efficacy data, the study showed that the treatment was generally safe and well-tolerated by the patients, with adverse events reportedly mild in severity.
These findings supported the launch of the Phase 2 trial in patients with Cushing’s syndrome. In the trial, roughly 30 patients are receiving escalating doses of relacorilant for a total of 12 weeks.
Patients were divided into two groups. The first group, which includes 17 patients, receives the lowest dose — 100 mg/day of relacorilant for four weeks, followed by 150 mg/day for four weeks, and then 200 mg/day for the last four weeks. The second group, called the high-dose cohort, is treated with a similar regimen but with a starting dose of 250 mg/day and a final dose of 350 mg/day.
Patients in the low-dose group had a significant improvement in their glucose tolerance and a 60% increase in blood osteocalcin.
In addition, the treatment reduced the blood pressure in 45% of patients with uncontrolled high blood pressure from cortisol excess. Importantly, the results after 12 weeks of relacorilant were similar to those seen after six months of Korlym treatment.
Safety data continues to show a positive profile, with no evidence of serious adverse effects and no affinity toward the progesterone receptor, which is a major drawback of Korlym.
“Relacorilant’s clinical results are striking because the doses these patients received were the study’s lowest. We did not expect patients to experience any meaningful clinical benefit, but they clearly did,” Robert S. Fishman, MD, chief medical officer of Corcept, said in the release. “We look forward to presenting data from these low-dose patients at the AACE meeting next week. With the trial’s final, high-dose cohort fully enrolled, we will have final data in the third quarter.”
Supported by these preliminary data, Corcept has accelerated the preparations for a Phase 3 trial on relacorilant in Cushing’s syndrome patients.