Mineralys Therapeutics Announces Phase 2 Explore-CKD Trial Met Its Primary Endpoint; Publishes Full Results In The Journal 'Kidney International'

The Explore-CKD trial evaluated the efficacy and safety of lorundrostat, an aldosterone synthase inhibitor, added to guideline-directed background therapy in 59 participants with uncontrolled hypertension, stage 1 to 3b CKD and albuminuria (albumin loss in the urine), an early manifestation of kidney damage.

Key Findings from Explore-CKD

Explore-CKD randomized 59 participants at 42 sites in the United States. Participants had a mean age of 64.6 years and a mean body mass index of 33.1 kg/m2, and 76% had type 2 diabetes. Of the participants, 30.5% were female, 16.9% were Black or African American and 42.4% were Hispanic or Latino. At baseline, mean automated office systolic blood pressure (AOSBP) was 149 mmHg, UACR (urinary albumin-to-creatinine ratio, an indicator of kidney protein loss) was 516.8 mg/g and mean estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73m2 based on cystatin C. Overall, 64.4% of participants were taking three or more antihypertensive medications.

The primary efficacy endpoint was the change from baseline in systolic blood pressure at week four in the active versus placebo treatment period. At week four, lorundrostat 25 mg once daily achieved a 9.3 mmHg reduction in AOSBP, compared with a 1.8 mmHg reduction for placebo, yielding a placebo-adjusted reduction of 7.5 mmHg (95% CI, -12.3 to -2.7; p=0.0024). Automated office diastolic blood pressure was reduced by 3.9 mmHg with lorundrostat and 1.4 mm Hg with placebo.

Lorundrostat also reduced UACR by 30.5% from baseline and by 25.6% placebo-adjusted (p=0.0015) at week four. The placebo-adjusted reductions were also significant for 24-hour UACR (26.1%; p<0.0001) and 24-hour urine protein-to-creatinine ratio (22.1%; p=0.0002).

Serum aldosterone decreased by 41.5% with lorundrostat and increased by 1.8% with placebo, and plasma renin activity rose by 75.2% and 4.2%, respectively. No clinically meaningful changes in serum cortisol were observed in either treatment sequence.

The nature and incidence of adverse events were similar to those in prior lorundrostat trials and consistent with its mechanism of action.