Mineralys Therapeutics' Hypertension Drug Shows Promise in Late-Stage Trials

Mineralys Therapeutics has reported positive results from two clinical trials of its experimental hypertension drug lorundrostat, potentially setting the stage for a new entrant in the competitive blood pressure medication market. The company's shares surged following the announcement, reflecting investor optimism about the drug's prospects.

Phase II/III Trial Results

In the pivotal Phase III Launch-HTN trial, lorundrostat demonstrated significant efficacy in reducing blood pressure among patients with uncontrolled or resistant hypertension. The study, which enrolled 1,083 participants already taking two to five antihypertensive medications, showed that patients receiving 50 mg of lorundrostat experienced a placebo-adjusted reduction in systolic blood pressure of 9.1 mmHg after six weeks of treatment.

The benefits appeared to increase over time, with patients on the lower dose showing an 11.7 mmHg decrease in blood pressure at 12 weeks when adjusted for placebo. Notably, the efficacy was consistent regardless of whether patients had uncontrolled hypertension (using two background antihypertensives) or resistant hypertension (using three to five antihypertensives).

Concurrently, the Phase II Advance-HTN trial, involving 285 patients with uncontrolled or treatment-resistant hypertension, met its primary endpoint. Patients receiving 50 mg of lorundrostat experienced a placebo-adjusted reduction in blood pressure of 7.9 mmHg, measured using a 24-hour average at week 12.

Safety Profile and Mechanism of Action

Lorundrostat is an inhibitor of aldosterone synthase, the enzyme responsible for producing aldosterone, a hormone linked to hypertension. This mechanism of action distinguishes it from many existing antihypertensive treatments.

The safety profile of lorundrostat appears favorable, with relatively low rates of serious adverse events. In the Launch-HTN trial, only four patients across the two dosing groups reported treatment-related adverse events. The incidence of hyperkalemia, a side effect of particular interest given the drug's mechanism, was 1.1% and 1.5% in the 50 mg and dose escalation arms, respectively.

Market Implications and Industry Context

The positive results for lorundrostat come at a time of significant activity in the hypertension treatment space. In March 2024, Idorsia received FDA approval for Tryvio, an endothelin receptor antagonist, marking the first new mechanism for hypertension treatments in decades. Other companies, including Alnylam and George Medicines, have also recently announced late-stage data for their antihypertensive candidates.

Mineralys CEO Jon Congleton expressed confidence in lorundrostat's potential, stating, "We believe the clinical profile observed for lorundrostat supports the potential regulatory approval of this novel agent and its significant commercial value." The company plans to present more detailed findings at the upcoming American College of Cardiology Scientific Sessions.

Investors reacted positively to the news, with Mineralys' shares climbing by approximately 50% following the announcement. Analysts from Stifel and Evercore ISI have characterized the results as potentially practice-altering and described lorundrostat as a "derisked, almost-commercial stage cardiometabolic asset."

As Mineralys prepares for potential regulatory submissions, the company faces competition from established players like AstraZeneca, which entered the aldosterone synthase inhibitor space through its $1.8 billion acquisition of CinCor Pharma in 2023. The coming months will likely see increased attention on the hypertension market as these new treatment options progress towards commercialization.