On August 30, 2026, ESC Congress 2026 in Munich ran LUMINARA as a Hot Line presentation. Circulation published the primary paper the same day. James L. Januzzi Jr. (Baim Institute for Clinical Research, Massachusetts General Hospital, Harvard Medical School) presented an AstraZeneca-funded Phase 2b test of AZD5462, a once-daily oral agonist of relaxin family peptide receptor 1 (RXFP1), added to standard heart-failure therapy.
AZD5462 is not a peptide drug. Granberg et al. (Journal of Medicinal Chemistry, 2024) call it a selective oral allosteric RXFP1 agonist and a small-molecule pharmacological mimetic of relaxin H2 signaling. It targets the receptor for the pregnancy peptide hormone relaxin. A receptor agonist is not the hormone.
The reduced-ejection-fraction primary approached, and missed, conventional statistical significance. The mid-range ejection-fraction cohort showed vasodilation on a hemodynamic surrogate. The authors say larger outcomes trials are warranted. That is not FDA approval and not a cardiovascular-death or heart-failure-hospitalization win.
This is the 10:07 Research Roundup. It is not an Industry News incretin story. AZD5462 is an investigational AstraZeneca tablet, not a SLU-PP-332 catalog chemical.
What happened on August 30
The ESC press release and the ACC clinical summary describe the same session: Hot Line 6, 30 August 2026, with simultaneous Circulation publication.
Januzzi et al., Circulation, 30 August 2026 (PMID 42668430, doi 10.1161/CIRCULATIONAHA.126.082763), is the primary results paper. PubMed lists it as online ahead of print. This article uses the PubMed abstract plus the ESC and ACC numbers. It does not treat a paywalled full text as fetched.
ClinicalTrials.gov NCT06299826 is the registry record. Status is completed. Actual enrollment is 375. Actual start is 4 June 2024. Actual primary completion and study completion are 10 February 2026. The sponsor is AstraZeneca.
The design paper is Quintana-Hayashi, Connolly, Millegård, and colleagues, ESC Heart Failure, 2026 (PMID 41711202, doi 10.1093/eschf/xvaf007, PMC13232748). ESC cites that rationale paper. Planned size there was about 360 (220 plus 140). The completed trial randomized 235 plus 140.
What AZD5462 is
Relaxin is a peptide hormone of pregnancy. RXFP1 is its main receptor. Circulation's background states that stimulating RXFP1 experimentally reduces systemic vascular resistance and afterload, improves organ perfusion, and fosters reverse cardiac remodeling. That is the trial hypothesis. It is not a LUMINARA outcomes result.
AZD5462 is AstraZeneca's once-daily oral small-molecule selective agonist of that receptor. Granberg et al. (PMID 38502782) identified it by optimizing an earlier tool agonist, AZ7976. The chemistry paper says AZD5462 activates a panel of downstream pathways similar to relaxin H2 and does not modulate relaxin H2-mediated cAMP responsiveness. Those are 2024 dish and animal claims, not the 2026 Phase 2b readout.
Ryberg et al. (Molecular Therapy Advances, 2026, PMID 42137267) also call AZD5462 a novel oral small-molecule RXFP1 agonist designed for chronic use. That paper reports non-human-primate HFrEF work and Phase 1 healthy-volunteer tolerability. Those primate remodeling figures are animal data. They are not LUMINARA.
AZD5462 is not SS-31 (elamipretide). Sharing a heart-failure conversation is not sharing a molecule. It is not ARA-290. It is not a research-vendor "relaxin" vial.
| Thing | What it is | What LUMINARA can show |
|---|---|---|
| Relaxin H2 | Endogenous pregnancy peptide hormone | Class context, not the study drug |
| RXFP1 | Relaxin family peptide receptor 1 | The drug target |
| AZD5462 | Oral small-molecule allosteric RXFP1 agonist (Granberg 2024) | 24-week surrogates on top of HF therapy |
| LUMINARA | Phase 2b, double-blind, placebo-controlled, dose-ranging (NCT06299826) | ESVi and SVRi, plus safety |
| Outcomes win | CV death or HF hospitalization in a powered trial | Not this study |
A COA check can test whether a certificate names a real lab. It cannot turn a catalog chemical into the AstraZeneca tablet. AZD5462 is not approved for human use outside trials.
Study design
LUMINARA is an international, multicenter, double-blind, placebo-controlled, dose-ranging Phase 2b trial. Circulation randomized adults with chronic heart failure and left ventricular ejection fraction of 35% or less (Cohort A) or 41% to 55% (Cohort B), 1:1:1:1, to placebo or AZD5462 20 mg, 80 mg, or 360 mg once daily.
Patients were already on stable, maximally tolerated standard-of-care therapy. Circulation calls baseline guideline-directed medical therapy excellent. ESC says the same setup: on top of existing therapies, not instead of them.
| Item | Published figure | Source |
|---|---|---|
| Phase | 2b, dose-ranging | NCT06299826, Circulation, ESC |
| Randomization | 1:1:1:1, double-blind, placebo-controlled | Circulation, ESC, NCT |
| Cohort A | LVEF ≤35%, n = 235 randomized | Circulation |
| Cohort B | LVEF 41-55%, n = 140 randomized | Circulation |
| Total N | 375 actual | Circulation, NCT |
| Sites | 57 sites, 10 countries (Circulation). ESC press release said 69 sites. | Circulation abstract vs ESC |
| Treatment | Once-daily oral tablets for 24 weeks | ESC, design paper, NCT arms |
| Primary analysis window | Change from baseline to week 25 | Circulation, NCT |
| Cohort A primary | Change in end-systolic volume index (ESVi) | Circulation, ESC, ACC |
| Cohort B primary | Change in systemic vascular resistance index (SVRi) | Circulation, ESC, ACC |
| Mean age | 65 years (A), 70 years (B) | Circulation |
| Sex | 88% male (A), 69% male (B) | Circulation |
The design paper named echocardiographic parameters, health status, cardiorenal biomarkers, and pharmacokinetics as secondaries. ESC says secondary effects, including LVEF change, were also greatest at the lowest dose. Circulation's fetched abstract does not print those numbers. This article does not invent them.
What the numbers show
Cohort A (LVEF ≤35%). Circulation reports that AZD5462 20 mg produced a placebo-adjusted ESVi change from baseline of −5.4 mL/m² at week 25 (95% CI −10.9 to 0.1; P=0.054). The confidence interval crosses zero. The P value does not meet the conventional 0.05 threshold. ESC and ACC repeat the 5.4 mL/m² figure and the 0.054 P value. ESC says the lowest dose had the most beneficial effects on cardiac function, and that secondary effects including LVEF change were also greatest at that dose. Circulation's fetched abstract does not publish a dose-response table for 80 mg or 360 mg on ESVi. Do not read a missed primary as reverse-remodeling proof.
Cohort B (LVEF 41-55%). Circulation says AZD5462 produced significant placebo-adjusted SVRi reductions at week 25 across all dose groups (all P<0.05). ESC gives the percentages: about 19%, 21%, and 15% at 20 mg, 80 mg, and 360 mg, all p≤0.021. Those percentages are the ESC press-release figures. They are hemodynamic surrogates, not hospitalization or death rates.
Safety, as reported. Circulation says treatment was well tolerated compared with placebo. ESC and ACC say the incidence of adverse events was low, with no evidence for an excess among people on AZD5462. Mild blood-pressure lowering was noted. Significant hypotension was not higher than placebo. ESC says there was no evidence for significant volume overload of the kind previously seen with higher doses of relaxin-like drugs. That last clause is the authors' comparison, not a named prior trial table in the fetched texts.
Januzzi's on-stage line, carried by ESC and ACC: target engagement was demonstrated in both cohorts, with signs of improved cardiac function at the lowest dose on top of standard care, and larger randomized trials focused on outcomes are now warranted. ACC also quotes a related editorial by Andrew P. Ambrosy and Adrian F. Hernandez calling LUMINARA informative and saying the findings establish biological plausibility. That is editorial language, not an outcomes result.
Trial doses
AZD5462 is not approved for human use outside clinical trials. The table reports what LUMINARA assigned. It is not a dosage guide and it is not a consumer protocol.
| Setting | Reported exposure | Source |
|---|---|---|
| Cohort A and B, low | AZD5462 20 mg once daily, oral tablet, 24 weeks | Circulation, ESC, ACC |
| Cohort A and B, medium | AZD5462 80 mg once daily, oral tablet, 24 weeks | Circulation, ESC, ACC |
| Cohort A and B, high | AZD5462 360 mg once daily, oral tablet, 24 weeks | Circulation, ESC, ACC |
| Control | Matching placebo once daily, 24 weeks | Circulation, NCT |
| NCT arm language | Low, medium, and high film-coated tablets, once daily, 24 weeks (milligrams named in the results papers, not in the public arm titles) | NCT06299826 |
Every dose section in this article is a trial assignment. AZD5462 is not approved for human use outside trials. That does not make 20 mg an approved dose. It also does not make 80 mg or 360 mg an approved dose.
What this does not mean
- It is not an outcomes win. LUMINARA measured ESVi and SVRi. It did not publish a powered effect on cardiovascular death or heart-failure hospitalization.
- It is not FDA approval. AZD5462 remains investigational. It is not approved for heart failure or any other use.
- Cohort A is not definitive reverse remodeling. The 20 mg ESVi change was −5.4 mL/m², 95% CI −10.9 to 0.1, P=0.054. That approaches, and does not meet, the conventional significance line.
- Cohort B vasodilation is not a clinical-outcomes claim. A lower SVRi is a hemodynamic signal. ESC's 19% / 21% / 15% figures are not mortality reductions.
- A lowest-dose hint is not a labeled regimen. ESC said the lowest dose looked best on cardiac function. That is still a Phase 2b reading.
- AZD5462 is not a peptide. Relaxin is the peptide hormone. The tablet is a small-molecule receptor agonist.
- Monkey or Phase 1 packages are not this readout. Granberg 2024 and Ryberg 2026 are chemistry and translational context.
- This is not medical advice, and it is not a consumer dosing protocol.
- This is not a GLP-1, GIP, or amylin rewrite.
What did not change
AZD5462's unapproved status did not change on 10 September 2026. No PeptidePrices research page was created or updated. No research-vendor listing became the trial tablet. Heart-failure standard care did not gain a new approved oral RXFP1 agonist.
Earlier RXFP1 and relaxin programs had tolerability and dose problems. ESC says earlier attempts were unsuccessful in part because of side effects possibly related to supra-physiological dosing. Ryberg 2026 says prior clinical studies using injectable short- or long-acting relaxin analogues have not delivered sustained benefits. Those sentences are the sourced history used here. This article does not invent a named prior-trial table beyond that.
Limitations
The Circulation full text was not fetched. Numbers that appear only in figures or supplements are omitted. ESC and Circulation disagree on site count (69 versus 57). This article keeps both and treats Circulation as the peer-reviewed count.
Cohort A is 235 people. Cohort B is 140. Those samples are too small for outcomes. The trial was funded by AstraZeneca. Multiple Circulation authors list AstraZeneca affiliations. ESC discloses that Januzzi received significant grant support and modest consulting income from the sponsor. Sponsorship does not erase the P=0.054 interval.
The 24-week treatment window and the week-25 analysis are not the same clock. ESC and the design paper describe 24 weeks of dosing. Circulation and NCT analyze change to week 25. This article reports that split.
What to watch next
- A powered outcomes protocol. Januzzi asked for larger randomized trials focused on outcomes. Until one reads out, LUMINARA stays a surrogate study.
- Whether 20 mg remains the dose taken forward. ESC said the lowest dose looked best on cardiac function. That choice is not a label.
- How later papers treat the Cohort A miss. P=0.054 with a confidence interval that includes zero is not a win to relabel later as "significant remodeling."
- Independent confirmation that is not AstraZeneca-funded. The primary paper, the design paper, and the chemistry paper share the sponsor's footprint.
- Named comparisons to earlier injectable relaxin analogs. ESC and Ryberg give the class overhang. They do not reprint those older tables here.
FAQs
Is AZD5462 a peptide?
No. It is an oral small-molecule allosteric agonist of RXFP1, the receptor for the pregnancy peptide hormone relaxin. Granberg 2024 is the chemistry source for that identity.
Did LUMINARA prove AZD5462 treats heart failure?
No. It is a Phase 2b surrogate and hemodynamic study. Authors say larger outcomes trials are warranted. That is not proof of fewer deaths or hospitalizations.
What did the primary endpoints show?
In Cohort A, 20 mg changed ESVi by −5.4 mL/m² versus placebo (95% CI −10.9 to 0.1; P=0.054). In Cohort B, Circulation reports significant SVRi reductions at all doses (all P<0.05). ESC gives about 19%, 21%, and 15% at 20, 80, and 360 mg (all p≤0.021).
What dose was used?
LUMINARA assigned 20 mg, 80 mg, or 360 mg once daily, or placebo, as oral tablets for 24 weeks. AZD5462 is not approved for human use outside trials. That does not make 20 mg an approved dose.
Is AZD5462 FDA-approved?
No. It is investigational. It is not approved for heart failure or any other use.
Who funded LUMINARA?
AstraZeneca. ESC states the funding and discloses Januzzi's grant support and consulting income from the sponsor. Several Circulation authors list AstraZeneca affiliations.
This article is for general informational purposes only and is not medical advice. Talk to a licensed clinician about personal medical decisions. AZD5462 is an investigational small-molecule RXFP1 agonist studied in a Phase 2b heart-failure trial. Nothing here is a dosing protocol, an availability claim, or a recommendation to obtain an unapproved product.
Continue your research
- SLU-PP-332 is also not a peptide
- ARA-290 human trial doses
- SS-31 (elamipretide)
- COA Authenticity Checker
Sources
- ESC Press Office. Novel drug shows promise in an early phase trial in heart failure. ESC Congress 2026. 30 August 2026
- American College of Cardiology. LUMINARA: oral relaxin receptor agonist AZD5462 in treating chronic HF. 30 August 2026
- Januzzi JL Jr, et al. Oral relaxin receptor agonist AZD5462 in participants with chronic heart failure: primary results from the LUMINARA trial. Circulation. 2026 Aug 30. doi 10.1161/CIRCULATIONAHA.126.082763. PMID 42668430
- ClinicalTrials.gov NCT06299826. Phase IIb two-cohort dose-ranging study of AZD5462 in stable chronic heart failure
- Quintana-Hayashi MP, et al. Phase 2b trial of an oral relaxin family peptide receptor 1 agonist in patients with chronic heart failure: rationale and design. ESC Heart Fail. 2026;13(3):xvaf007. doi 10.1093/eschf/xvaf007. PMID 41711202
- Granberg KL, et al. Discovery of clinical candidate AZD5462, a selective oral allosteric RXFP1 agonist for treatment of heart failure. J Med Chem. 2024;67(6):4419-4441. PMID 38502782
- Ryberg E, et al. The first oral relaxin receptor RXFP1 agonist for heart failure treatment: translational studies from non-human primates to humans. Mol Ther Adv. 2026;34(1):201674. PMID 42137267