New hypertension drugs show no advantage over older generics

Two new drugs for treatment-resistant hypertension, Baxfendy (baxdrostat) and lorundrostat, did not lower blood pressure much more than decades-old generic drugs and are even more expensive than what is considered a standard value in the healthcare market, according to a draft evidence report from the Institute for Clinical and Economic Review (ICER).

ICER released the draft report this week on AstraZeneca’s baxdrostat and Mineralys Therapeutics’ lorundrostat. Both belong to a new drug class called aldosterone synthase inhibitors (ASIs), which lower blood pressure by reducing the body's production of aldosterone rather than blocking its receptor the way older drugs such as Aldactone (spironolactone) and Inspra (eplerenone) do.

The FDA approved baxdrostat in May 2026, and lorundrostat has a Prescription Drug User Fee Act (PDUFA) decision date in December.

Hypertension affects nearly half of U.S. adults, contributes to more than 600,000 U.S. deaths a year and costs an estimated $219 billion annually in medical spending, according to the report. About 7 million Americans have apparent treatment-resistant hypertension, meaning their blood pressure stays above goal despite taking three or more antihypertensive drugs at the maximum tolerated doses.

ICER noted they conduct these reviews to give payers, clinicians and patients an independent assessment of a drug's comparative effectiveness and fair price. The overall draft report is planned to be revised based on public comment ahead of a vote by the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC).

To conduct this study, ICER researchers built a network meta-analysis pooling randomized, placebo-controlled trials of baxdrostat and lorundrostat, most lasting 6 to 26 weeks, comparing the drugs with spironolactone, eplerenone and amiloride, formerly sold as Midamor or Moduretics before it was discontinued. The use of baxdrostat and lorundrostat was also compared with amlodipine in patients on two antihypertensive drugs who had not yet tried a third, since no head-to-head trials exist.

ICER then built an economic model, using a lifetime time horizon and a U.S. healthcare sector perspective, to estimate cost per quality-adjusted life year (QALY) gained for each drug against its comparators.

It was found that in patients with resistant hypertension, baxdrostat and lorundrostat reduced systolic blood pressure by about 11 mmHg and 9 mmHg versus the placebo. Reductions ICER found were not statistically different from the roughly 7-to-10-mmHg reductions produced by spironolactone, eplerenone and amiloride, though this came with much uncertainty. ICER rated the evidence “promising but inconclusive” for both ASIs against those three generics.

In patients earlier in treatment, neither drug beat amlodipine on blood pressure either, and ICER rated the drugs “comparable or inferior” to that far cheaper generic. On cost, ICER’s economic model used $900 for a 30-tablet supply as baxdrostat’s price, citing wholesale acquisition cost (WAC) data from Red Book, and applied the same price as a placeholder for lorundrostat, which is still under FDA review.

Against spironolactone and amiloride, baxdrostat’s cost came to roughly $833,000 and $851,000 per QALY; against eplerenone, it topped $2 million. Lorundrostat’s ratios, using the placeholder price, ranged from about $1.4 million to nearly $1.5 million per QALY, and against eplerenone specifically, it was projected to cost more while delivering less benefit. All of those figures fell significantly above the $100,000-to-$150,000-per-QALY range ICER typically uses to judge value.

The drugs did seem easier to tolerate over spironolactone when it came to hyperkalemia, which occurred in 10.2% of patients on the higher, 2-mg dose of baxdrostat (6.6% at the lower 1-mg dose) and 2.5% of patients on lorundrostat, compared with 17.5% on spironolactone. The report doesn’t include gynecomastia data specific to baxdrostat or lorundrostat, a side effect that has limited spironolactone’s use in some patients, with rates ranging from 3.9% to 6% in observational studies.

ICER also flagged bigger gaps in the evidence: no published trial of either drug has measured its effect on cardiovascular events, the longest baxdrostat trial ran only 26 weeks, and the pivotal trials excluded patients with advanced chronic kidney disease (CKD), a group at elevated risk of hyperkalemia.

“Although there appears to be no statistically significant difference in blood-pressure lowering between agents, there were small differences (2-4 mmHg) between the ASI agents compared with eplerenone or amiloride that, if real, could over years result in clinically significant differences in outcomes,” ICER’s researchers wrote in the report.

ICER is accepting public comments on the draft through Sept. 9, and the Midwest CEPAC will vote on the report’s key questions during a virtual meeting Oct. 29.