MLYS lorundrostat

Uncontrolled or resistant hypertension · Mineralys · NDA

Of 100 applications in this same position, about 88 get approved.

Until the FDA deadline78d

Base rate76%

Gap+12pts

PDUFA target date 2026-12-22the FDA may act earlier or later

Summary

FDA approval of lorundrostat in this review cycle is put at 88%, above the 76% base rate for first-time applications from smaller companies. Both pivotal trials met their primary endpoints, lowering systolic pressure 9.1 and 7.9 mmHg more than placebo. In May 2026 FDA approved baxdrostat, the first drug of the same class, for an almost identical indication on blood-pressure data alone, without an advisory committee or special restrictions. Raised potassium, low sodium and reduced kidney function are known class effects that FDA has handled through labeling. The main unknown is manufacturing: this is the company's first product, its contract manufacturers are not named, and no inspection results are public. The FDA goal date is 22 December 2026.

Recorded 2026-10-05 08:21 UTC · v1Proof ↓

Evidence · 7 items

Why 88%, not 76%

Indication

Hypertension in adults, in combination with other antihypertensive drugs (uncontrolled or resistant hypertension)

76% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast differs.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▲ SupportsLarge FDA approved the first drug of this class in May 2026 for almost the same indication

On 15 May 2026 FDA approved AstraZeneca's Baxfendy (baxdrostat), the first aldosterone synthase inhibitor, for "the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adults who are not adequately controlled on other agents". Lorundrostat's application seeks "the treatment of adult patients with hypertension in combination with other antihypertensive drugs". The baxdrostat approval rested on blood-pressure lowering in one phase 3 trial (BaxHTN, 794 patients randomized): seated systolic pressure at week 12 fell 9.8 mmHg (2 mg) and 8.7 mmHg (1 mg) more than on placebo, both p<0.0001. The label states that no controlled trial shows fewer cardiovascular events with the drug itself. It has no boxed warning and no contraindications; hyperkalemia and hyponatremia are warnings managed by blood tests. The approval letter says the application was not referred to an advisory committee because it "did not raise significant public health questions" and there were "no controversial issues"; the studies it requires after approval cover only children, lactation and pregnancy. The letter was signed by the director of FDA's Office of Cardiology, Hematology, Endocrinology, and Nephrology, whose remit includes hypertension drugs. Limits of the precedent: baxdrostat came from a large company under priority review, and its approval says nothing about how lorundrostat is manufactured.

Source: FDA approval letter, NDA 219878, signed 2026-05-15: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/219878Orig1s000ltr.pdf; Baxfendy prescribing information, revised 5/2026: https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219878Orig1s000lbl.pdf; Mineralys 8-K, 2026-03-09: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000048/mlys-20260306.htm; HCPLive, 2025-12-02 (priority review): https://www.hcplive.com/view/fda-accepts-priority-review-nda-of-baxdrostat-for-uncontrolled-hypertension
02▲ SupportsMedium Both pivotal trials met their primary endpoints clearly

Launch-HTN (phase 3; 1,083 adults taking 2 to 5 blood-pressure medicines, 159 sites in 13 countries; JAMA 2025): at week 6, automated office systolic pressure fell 16.9 mmHg on lorundrostat 50 mg and 7.9 mmHg on placebo, a difference of 9.1 mmHg (95% CI 4.9 to 13.3; P<.001). At week 12 the difference was 11.6 mmHg for 50 mg (p<0.0001) and 8.4 mmHg for the arm allowed to increase to 100 mg (p=0.0016). Advance-HTN (phase 2, designated pivotal; 285 adults still hypertensive on a standardized regimen; NEJM 2025): 24-hour ambulatory systolic pressure at week 12 fell 7.9 mmHg more than on placebo with 50 mg (97.5% CI 2.6 to 13.3) and 6.5 mmHg more in the dose-adjustment arm (97.5% CI 1.2 to 11.8). Supporting trials point the same way: Target-HTN (200 patients; 9.6 mmHg for 50 mg, P=.01) and Explore-CKD (59 patients with kidney disease; 7.5 mmHg with 25 mg, p=0.0024). Explore-OSA missed its primary endpoint, a sleep-apnea measure that is not part of this application; blood pressure still fell 6.2 mmHg more than on placebo. These effects are in the same range as baxdrostat's. The 100 mg dose added nothing over 50 mg; the company has said it is seeking 25 mg and 50 mg.

Source: Launch-HTN, JAMA 2025;334:409-418: https://pubmed.ncbi.nlm.nih.gov/40587141/; Advance-HTN, N Engl J Med 2025;392:1813-1823: https://pubmed.ncbi.nlm.nih.gov/40267417/; Target-HTN, JAMA 2023;330:1140-1150: https://pubmed.ncbi.nlm.nih.gov/37690061/; Explore-CKD, Kidney Int 2026: https://pubmed.ncbi.nlm.nih.gov/42778148/; Mineralys 10-K filed 2026-03-12: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000056/mlys-20251231.htm; Mineralys 8-K, 2026-03-09 (Explore-OSA): https://www.sec.gov/Archives/edgar/data/1933414/000193341426000048/mlys-20260306.htm; Investing.com report of the Wells Fargo conference, 2026-09-09 (doses sought): https://in.investing.com/news/stock-market-news/mineralys-at-wells-fargo-conference-lorundrostat-launch-takes-shape-93CH-5587269
03▲ SupportsSmall No cortisol suppression, and a safety database at least as large as the one described in the first approval's label

The long-standing worry with this class is that it also blocks cortisol production. In Launch-HTN no participant on lorundrostat had glucocorticoid deficiency confirmed by stimulation testing, and Target-HTN reported no cortisol insufficiency; Baxfendy's label likewise reports no effect on stimulated cortisol. In Launch-HTN serious adverse events were less frequent on lorundrostat (2.2% and 0.7%) than on placebo (3.0%), and the only death was in the placebo arm. The two pivotal trials randomized 1,001 patients to lorundrostat (811 + 190), and 1,076 patients entered the Transform-HTN extension study, which offers up to 52 weeks of open-label treatment, includes a randomized withdrawal phase and supported the application. For comparison, Baxfendy's label describes 12-week controlled data from 774 treated patients and long-term data from 192 and 172 patients. How many lorundrostat patients in the application were treated for a year or more has not been published; long-term results are due at the American Heart Association meeting on 8 November 2026.

Source: Launch-HTN, JAMA 2025 (full text, Table 3): https://pmc.ncbi.nlm.nih.gov/articles/PMC12210145/; Target-HTN, JAMA 2023: https://pubmed.ncbi.nlm.nih.gov/37690061/; Advance-HTN, N Engl J Med 2025: https://pubmed.ncbi.nlm.nih.gov/40267417/; Mineralys 10-K filed 2026-03-12: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000056/mlys-20251231.htm; ClinicalTrials.gov NCT05968430 (Transform-HTN): https://clinicaltrials.gov/study/NCT05968430; Baxfendy prescribing information, sections 6.1 and 12.2: https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219878Orig1s000lbl.pdf; Mineralys press release, 2026-09-23: https://ir.mineralystx.com/news-events/press-releases/detail/116/mineralys-therapeutics-transform-htn-open-label
04▼ AgainstSmall Potassium, sodium and kidney-function effects, more marked in the higher-risk trial

Lorundrostat raises potassium, lowers sodium and reduces measured kidney function more often than placebo. In Launch-HTN the published adverse events of special interest were hyperkalemia in 2.0% and 2.6% of the lorundrostat arms against 0.4% on placebo, hyponatremia in 6.9% and 10.4% against 3.3%, and reduced kidney function in 3.0% and 3.3% against 0.7%; fewer than 1% stopped treatment for any one of these. Potassium above 6.0 mmol/L was measured in 1.1% and 1.5% (0.6% and 1.1% after repeat testing). In Advance-HTN, where every patient was on an optimized regimen that included a diuretic and an angiotensin receptor blocker, potassium above 6.0 mmol/L occurred in 5.3% and 7.4% of the lorundrostat arms and in no one on placebo (2.1% and 3.2% after repeat testing), and serious adverse events were more frequent (6.4% and 8.4% against 2.1%); one death in the dose-adjustment arm was judged unrelated to the drug. In Explore-CKD confirmed hyperkalemia occurred in 3 of 58 patients (5%) on 25 mg and in none on placebo. Published pooled analyses of the same trials put the relative risk of hyperkalemia between 3.19 and 11.63. FDA dealt with the same effects for baxdrostat through warnings and monitoring, so these findings are more likely to shape the label than to block approval. Open points are how FDA counts potassium readings that were not confirmed on repeat testing, and whether the 25 mg dose, studied mainly in a 59-patient, four-week trial, is adequately supported.

Source: Launch-HTN, JAMA 2025 (full text, Table 3): https://pmc.ncbi.nlm.nih.gov/articles/PMC12210145/; Mineralys 10-K filed 2026-03-12 (safety results of both pivotal trials and Explore-CKD): https://www.sec.gov/Archives/edgar/data/1933414/000193341426000056/mlys-20251231.htm; Advance-HTN, N Engl J Med 2025: https://pubmed.ncbi.nlm.nih.gov/40267417/; NephJC commentary on Advance-HTN: http://www.nephjc.com/news/advance-htn-lorundrostat; Explore-CKD, Kidney Int 2026: https://pubmed.ncbi.nlm.nih.gov/42778148/; umbrella review, Am J Cardiovasc Drugs 2026;26:603-619: https://pubmed.ncbi.nlm.nih.gov/42489850/; Baxfendy prescribing information, sections 5 and 6.1: https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219878Orig1s000lbl.pdf
05▲ SupportsSmall No advisory committee expected, and the company describes a routine review

Mineralys's quarterly reports of 6 May and 11 August 2026 both describe an advisory committee meeting as "not anticipated currently"; none was held for baxdrostat. The company received pre-submission feedback from FDA in October 2025, submitted the application in December 2025, and was notified of its acceptance on 6 March 2026; the 12-month timetable is that of a standard review, and no priority review was announced. On 11 August 2026 the chief executive called the dialogue with FDA "regular course" with "no surprises" and expected discussions on labeling and post-approval commitments in October or November; on 9 September management said the dialogue continued to be productive. Limits: all of this is the company's own account. No FDA document on this review is public, the outcomes of the mid-cycle and late-cycle steps have not been disclosed, and the company has filed no 8-K since 11 August 2026.

Source: Mineralys 10-Q filed 2026-05-06: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000084/mlys-20260331.htm; Mineralys 10-Q filed 2026-08-11: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000114/mlys-20260630.htm; Mineralys press release, 2025-11-10: https://www.sec.gov/Archives/edgar/data/1933414/000193341425000139/mlys2025q38kex991.htm; Mineralys 8-K, 2026-01-06: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000002/mlys-20260106.htm; Mineralys 8-K, 2026-03-09: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000048/mlys-20260306.htm; Q2 2026 results call transcript, 2026-08-11: https://www.fool.com/earnings/call-transcripts/2026/08/18/mineralys-mlys-q2-2026-earnings-call-transcript/; Investing.com report of the Wells Fargo conference, 2026-09-09: https://in.investing.com/news/stock-market-news/mineralys-at-wells-fargo-conference-lorundrostat-launch-takes-shape-93CH-5587269; FDA approval letter for Baxfendy: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/219878Orig1s000ltr.pdf; SEC EDGAR filing list for Mineralys (CIK 1933414), as of 2026-10-05
06▼ AgainstMedium Manufacturing cannot be checked, and this is the company's first product

Mineralys has never had a product approved and owns no manufacturing facilities; the active ingredient and the tablets are made entirely by contract manufacturers. None of them is named in the company's SEC filings, so their FDA inspection histories cannot be looked up. The annual report filed on 12 March 2026 says the company had no long-term supply agreements with any manufacturer, had not arranged redundant supply or a second source for all the raw materials it needs, and that the process used for current clinical material differs from the one used in earlier trials. The same report notes that FDA inspects the manufacturing facilities after an application is submitted. No inspection result, Form 483 or warning letter connected with lorundrostat is on public record, and the company has not commented on the manufacturing part of the review. On the other side, the product is a conventional once-daily tablet of a small molecule, a comparatively simple kind of product to make. This is the part of the application about which the least is publicly known.

Source: Mineralys 10-K filed 2026-03-12 (Manufacturing; risk factors on third-party manufacturers): https://www.sec.gov/Archives/edgar/data/1933414/000193341426000056/mlys-20251231.htm; Mineralys 10-Q filed 2026-08-11: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000114/mlys-20260630.htm; ClinicalTrials.gov NCT05968430 (tablet, administered orally): https://clinicaltrials.gov/study/NCT05968430
07▲ SupportsSmall The company is committing money and people on the assumption of approval

In June 2026 Mineralys paid Tanabe $200.0 million upfront to end its royalty obligations on lorundrostat and arranged a loan facility of up to $500.0 million. It drew $100.0 million; a further $150.0 million is to be drawn by 30 April 2027 once FDA approves the application, and the whole loan must be repaid early if approval has not come by 30 September 2027. Cash and investments were $661.4 million on 30 June 2026. In August the company said its commercial leadership was in place, initial sales territories had been identified and the sales organization would be established before the goal date. A new chief medical officer started on 10 August 2026; his predecessor, who led development and the filing, stays on full-time as an adviser. Limits: this shows what management and its lenders expect, not what FDA thinks.

Source: Mineralys 8-K, 2026-06-03 (license amendment and loan agreement): https://www.sec.gov/Archives/edgar/data/1933414/000162828026040024/mlys-20260602.htm; Mineralys 10-Q filed 2026-08-11: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000114/mlys-20260630.htm; Mineralys 8-K and press release, 2026-08-11: https://www.sec.gov/Archives/edgar/data/1933414/000193341426000112/mlys-20260805.htm and https://www.sec.gov/Archives/edgar/data/1933414/000193341426000112/mlys2026q28kex991.htm

What would change this forecast

01
Up: Mineralys reports that discussions with FDA on labeling and post-approval commitments have begun (it expects them in October or November 2026), or that the manufacturing sites have been inspected without significant findings.
02
Down: a Form 483 with significant observations, a warning letter or an adverse inspection classification at a maker of lorundrostat's active ingredient or tablets becomes public, or the company discloses manufacturing questions from FDA.
03
Down: FDA schedules an advisory committee, or the company's next quarterly report (expected in November 2026) no longer calls one "not anticipated" or stops describing the review as routine.
04
Down: the long-term Transform-HTN results on 8 November 2026 show a new safety problem, such as adrenal insufficiency or more severe hyperkalemia with longer treatment, or FDA tightens the safety labeling of Baxfendy.
05
Little change on its own: FDA extends the goal date after a major amendment. The reason given for the extension would matter more than the delay.
06
Void rather than no: Mineralys withdraws the application before FDA acts.

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

Medium

Manufacturing and inspection risk

Medium

Mineralys has no approved product and no manufacturing facilities of its own. The active ingredient and the tablets are made entirely by contract manufacturers that its SEC filings do not name, so their FDA inspection records cannot be checked, and no inspection outcome, Form 483 or warning letter linked to lorundrostat is on public record. The annual report of 12 March 2026 says the company had no long-term supply agreements, had not arranged a second source for all the raw materials it needs, and that the process for current clinical material differs from the one used in earlier trials. In its favour, the product is a conventional once-daily tablet of a small molecule, not a sterile or biological product. What cannot be judged: which sites are named in the application, whether FDA has inspected them and with what result, and whether the manufacturing section has drawn questions from FDA. The level is set at medium because of these unknowns, not because of any reported problem.

Record · version 1

Written on 2026-10-05, 78 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-05 08:21 UTC 88% Current version JSON ↓.ots ↓ ○ Timestamp submitted, awaiting block confirmation

Fingerprint

SHA-256341ca13d3841c5e304fdb66d7d29d55888bf38d0e5da549d7cd8093f7762055b

The fingerprint of the v1 file. It is what the timestamp commits to: change one character of the file and the fingerprint no longer matches.

Verify it yourself

Download the JSON file above and the .ots file of the same name into one folder.
Compute the SHA-256 of the file. It should match the fingerprint above.
Verify with OpenTimestamps. Once the timestamp is in a Bitcoin block, ots verify reports the block time if you run a Bitcoin node; without one, drop both files on the verifier at opentimestamps.org, or run ots info to see the block height and look it up in any block explorer. If the block time is before the FDA’s decision, the file cannot have been written afterwards.

pip install opentimestamps-client
shasum -a 256 v1_20261005T082133Z.json
ots verify v1_20261005T082133Z.json.ots
ots info v1_20261005T082133Z.json.ots

Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-12-20. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.