TOPLINE:

Adult patients with Cushing syndrome who completed a 22-week trial of relacorilant therapy and continued treatment for 12 additional weeks preserved hypertension control and sustained other cardiometabolic benefits compared with those who switched to placebo.

METHODOLOGY:

• Relacorilant is an investigational, nonsteroidal selective glucocorticoid receptor modulator that competitively and reversibly reduces excess cortisol activity without fully blocking the receptor; it was associated with notable benefits in patients with endogenous hypercortisolism (Cushing syndrome) in a phase 2 trial.
• Researchers conducted a phase 3 clinical trial to assess the efficacy and safety of relacorilant in patients with endogenous hypercortisolism with hypertension, hyperglycemia, or both.
• Participants received daily oral relacorilant (escalation from 100 mg up to 400 mg) for 22 weeks in an open-label phase.
• At 22 weeks, 62 patients who met response criteria (≥ 5 mm Hg decrease in blood pressure and/or significant glycemic improvement) were randomly assigned to continue relacorilant (400 mg or the highest tolerated dose; n = 30) or switch to placebo (n = 32) for 12 weeks in the randomized withdrawal phase.
• The primary outcome was loss of hypertension response during the randomized withdrawal phase, defined as a ≥ 5 mm Hg increase in blood pressure, change in antihypertensive medication owing to worsening hypertension, or treatment discontinuation.

TAKEAWAY:

• Continuing relacorilant was associated with lower odds of losing hypertension response at 12 weeks than switching to placebo (odds ratio, 0.17; P = .022).
• Patients with hyperglycemia who continued relacorilant maintained the improvements seen in the open-label phase; benefits were statistically significant over placebo at the 2-hour timepoint on the oral glucose tolerance test (P = .024).
• Patients in the relacorilant group also better maintained reductions in body fat and waist circumference achieved during the open-label phase, while those treated with placebo showed increases.
• The majority of treatment-emergent adverse events were mild to moderate. No cases of excessive glucocorticoid receptor antagonism, adrenal insufficiency, vaginal bleeding related to endometrial hypertrophy, drug-induced hypokalemia, or drug-induced QT interval prolongation were reported in either the open-label or randomized withdrawal phase.

IN PRACTICE:

“Patients with endogenous hypercortisolism of various causes given relacorilant during the randomized withdrawal phase were 5.9 times more likely to maintain hypertension response compared with those who received placebo,” the authors of the study wrote.

“The validation of the efficacy and safety of this novel agent [relacorilant] for what can be a life-limiting and devastating disorder is valuable for neuroendocrinologists,” an expert wrote in an accompanying editorial.

SOURCE:

The study was led by Rosario Pivonello, MD, PhD, Sezione di Endocrinologia, Diabetologia, Andrologia e Nutrizione Universita Federico II di Napoli, Naples, Italy. It was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The COVID pandemic affected participant retention during the study. The 12-week randomized withdrawal phase was likely too short to reflect changes in key endpoints such as A1c or weight. Additionally, the relatively small sample size and missing data may have affected the interpretation of results.

DISCLOSURES:

The study was funded by Corcept Therapeutics. Five authors declared being employees of Corcept Therapeutics. Some other authors reported receiving fees, grants, or research support; serving as consultants, speakers, or advisers; and holding other ties with various pharmaceutical companies, including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.