Post-hoc analysis supports association of BMI, reduced blood pressure with lorundrostat
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Key takeaways:
- Researchers found a median reduction in systolic blood pressure of 32 mm Hg.
- Results are consistent with pre-specified categorical analysis from the Target-HTN trial.
PHILADELPHIA — Obesity-associated dysregulated aldosterone is an endotype predictive of response to lorundrostat for patients with uncontrolled or treatment-resistant hypertension, according to data presented at ASN Kidney Week.
In a post-hoc analysis of the Target-HTN phase 2 trial, researchers identified a population of responders to lorundrostat (Mineralys), an orally administered, highly selective aldosterone synthase inhibitor for patients with uncontrolled hypertension and resistant hypertension. Lorundrostat was designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production.
Researchers found a median reduction in systolic blood pressure of 32 mm Hg. Consistent with the pre-specified categorical analysis from the Target-HTN trial that demonstrated an enhanced treatment response in patients with an elevated BMI, a post-hoc linear regression analysis demonstrated a statistically significant association between BMI and reduction in systolic blood pressure in patients with a BMI ranging from 22.5 kg/m2 to 40 kg/m2. The modeled reduction in observed systolic blood pressure was approximately 12 mm Hg at a BMI of 30 kg/m2 and 19 mm Hg at a BMI of 40 kg/m2.
The Target-HTN phase 2 randomized trial demonstrated treatment with lorundrostat at doses of 50 mg and 100 mg once daily led to a statistically and clinically significant reduction of systolic blood pressure in uncontrolled hypertensive patients who are on at least two background antihypertensive medications.
“We teach medical students that hyperaldosteronism, or increased aldosterone production causing hypertension, is due to adrenal tumors and nests of abnormal adrenal cortical cells, and this syndrome can often be detected by a simple blood test showing a low level of the kidney protein renin. In the Target-HTN trial, we tested this hypothesis and found the low renin approach was no longer very useful,” David M. Rodman, MD, chief medical officer of Mineralys, told Healio.
Rodman said categorizing patients by weight into obese or non-obese groups was a better predictor of treatment response as patients with obesity had a greater blood pressure reduction when taking lorundrostat.
According to a company press release, endotype identification from Target-HTN may represent a shift toward targeted, precision-directed therapy for the management of hypertension in future treatment paradigm. Additionally, the Ongoing Advance-HTN trial will further characterize hypertensive endotype for enhanced response to lorundrostat treatment.
“We believe that obesity is an important predictor of response, but we do not think that is the entire story. We continue to explore the characteristics of patients with exceptional response to lorundrostat and believe that we will be able to provide clinicians with a useful ‘toolkit’ to predict who should receive lorundrostat,” Rodman said.
References:
Cizman B, et al. TH-PO1121. Presented at: ASN Kidney Week; Nov. 1-5, 2023; Philadelphia.
Laffin LJ, et al. JAMA. 2023;doi:10.1001/jama.2023.16029.
Mineralys Therapeutics presents new post-hoc analysis from Target-HTN phase 2 trial of lorundrostat in late-breaking poster session at ASN Kidney Week 2023 Meeting. https://ir.mineralystx.com/news-events/press-releases/detail/31/mineralys-therapeutics-presents-new-post-hoc-analysis-from. Published Nov. 2, 2023. Accessed Nov. 2, 2023.
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