Novartis' pelacarsen failed to reduce the risk of cardiovascular death or emergencies such as heart attack or stroke compared with placebo in the Phase 3 HORIZON trial, despite earlier trials showing it drastically lowered Lp(a), a lipid-and-protein particle linked to severe heart problems. The outcome is a setback for Novartis and for the broader effort to target Lp(a), where Amgen and Eli Lilly are also developing therapies.
Novartis' Ionis-partnered Lp(a)-lowering drug failed to reduce patients' risk of heart attack, stroke, or other major cardiovascular events in its first late-stage trial. The result comes in the first phase 3 test of a drug aimed at Lp(a), a known cardiovascular risk factor, and undermines the strategy of targeting the molecule to cut cardiovascular risk. What changes is the outlook for Lp(a) reduction as a cardioprotective approach.
Italy's Menarini has signed its first obesity licensing deal with Beijing-based Gan & Lee Pharmaceuticals for bofanglutide, a twice-monthly GLP-1R agonist whose efficacy data were competitive with Zepbound and Wegovy. The agreement is Gan & Lee's first major out-licensing deal to a Western biopharma from its metabolic-disease-focused innovative pipeline. Further deal terms and development steps were not disclosed.
The ITACS trial is an international, double blind, placebo controlled randomised trial evaluating intravenous iron for treating anaemia before cardiac surgery.
The ITACS trial evaluated the efficacy of intravenous iron in patients with anaemia before cardiac surgery, using an international, multicentre, double blind, placebo controlled randomised design.
JAMA published a study on evolocimab and cardiovascular events in patients with diabetes without known significant atherosclerosis. The study examined evolocumab in this patient population.
Menarini Group will pay Gan & Lee Pharmaceuticals €62 million ($72 million) up front under a deal worth up to $771 million to register and commercialize Gan & Lee's GLP-1 bofanglutide in Europe. The Italian company takes the Chinese insulin maker's drug to the European market. Registration and commercialization work under the collaboration follows.
EMA's Pharmacovigilance Risk Assessment Committee has begun a review of all injectable iron-containing medicines over risks of hypophosphataemia and related bone problems such as osteomalacia. The review was triggered by reports questioning the effectiveness of current risk-minimisation measures for ferric carboxymaltose products, including serious cases after only one or two doses in people without recognised risk factors. PRAC will assess the benefit-risk balance and decide whether changes to marketing authorisations are needed.
Microfluidic-engineered glucose-responsive microspheres, using glucose oxidase as the sensing unit in a PLGA and acetalated dextran carrier, release insulin in response to glucose. Fabrication gave uniform, controllable microsphere size with stable batch-to-batch reproducibility. In STZ-induced diabetic mice, a single injection kept blood glucose normal for at least 20 hours, with no organ toxicity, no systemic inflammation and a low hypoglycemic index.
An orally bioavailable small molecule, 5-tetradecyloxy-2-furoic acid (TOFA), alleviated obesity, abnormal glucose homeostasis and fatty liver-related disease without affecting food intake or muscle mass. TOFA inhibits acetyl-CoA carboxylases 1 and 2 and activates PPARalpha/delta, raising energy expenditure and rebalancing lipid synthesis. It also acted more than additively with the incretin analogs semaglutide and tirzepatide to improve obesity, dyslipidemia and insulin resistance.
A subanalysis of the phase 3 Vesalius-CV trial in more than 12,000 high-risk adults without prior heart attack or stroke ties Repatha (evolocumab), added to statins or other LDL-C-lowering medicines, to a 20% reduction in all-cause mortality, with the benefit emerging within 18 months. Myocardial infarction risk fell 36%, with apparent benefit within six months. Results, published in Circulation, accompanied real-world data showing patients surviving a first cardiovascular event are 63% more likely to suffer a second heart attack, stroke or revascularization.
Once-weekly survodutide, a glucagon receptor-GLP-1 receptor dual agonist, produced mean body-weight reductions of 12.2% at 3.6 mg and 13.0% at 6.0 mg at week 76, versus 5.4% with placebo, in 725 adults with obesity but no diabetes. Weight loss of at least 5% occurred in 72.6% and 71.9% of the survodutide groups versus 46.3% on placebo (P<0.001). Gastrointestinal symptoms were the most common adverse events, and no deaths were reported.
The FDA has approved Eli Lilly's tirzepatide to reduce the risk of cardiovascular events in adults with type 2 diabetes who are at high cardiovascular risk. Tirzepatide, a GIP/GLP-1 receptor agonist, is described as the first and currently only agent of its class shown to lower the risk of myocardial infarction, stroke or cardiovascular death in this population, while also providing glycemic control and weight management. The indication has not yet been approved in China.
Semaglutide treatment of 20-month-old female C57BL/6 mice for 3 months improved physiological function, attenuated hallmarks of ageing and extended lifespan. In a longitudinal comparison with matched calorie restriction, semaglutide preserved baseline function and outperformed calorie restriction in exploratory drive, spatial memory and glucose control. The work frames GLP-1R activation as a calorie restriction mimetic acting partly through mechanisms beyond reduced food intake.
In the EPIDAURUS open-label randomized trial in patients with atrial fibrillation and acute coronary syndrome, 1 month of a DOAC plus a potent P2Y12 inhibitor (prasugrel or ticagrelor) was compared with DOAC plus clopidogrel and in-hospital aspirin. The trial stopped early after 602 of 1,474 planned patients on Data and Safety Monitoring Board safety concerns. Exploratory analyses showed higher BARC type ≥2 and ≥3 bleeding with potent inhibitors and no clear reduction in ischemic events.
A review by Royer, Grimsey and colleagues in the Biochemical Journal synthesizes evidence that p38 MAPKs, especially the p38α isoform, can be activated through atypical mechanisms independent of the upstream kinases MKK3 and MKK6. It compares interactors including TAB1, ZAP-70, the hepatitis C virus core protein and Toxoplasma gondii GRA24, and links this activation mode to cardiac ischemia, infection, inflammation and vascular dysfunction. The authors frame atypical p38 signaling as a distinct regulatory paradigm within MAPK signaling.
Allogeneic human induced pluripotent stem cell-derived cardiomyocytes injected into the myocardium during CABG met the safety primary endpoint in the HEAL-CHF trial (n = 20): no sustained ventricular tachycardia in the 1- to 6-month window and no tumorigenicity at 12 months. All 10 cell-treated patients developed accelerated idioventricular rhythm within 4 weeks, and 2 had ventricular tachycardia over 140 bpm that resolved after cardioversion. Cell therapy improved 6-min walk distance, myocardial perfusion and relative wall thickening beyond CABG alone, but not ejection fraction, ventricular volumes, scar size, NYHA class or quality-of-life scores.
Prime editing combined with somatic cell nuclear transfer produced pigs expressing proofreading-deficient POLG, the catalytic subunit of DNA polymerase gamma. The pigs accumulated elevated somatic mitochondrial DNA mutation loads and showed premature aging phenotypes, including weight loss, anemia, increased apoptosis, up-regulation of senescence-associated markers, and shortened life span. The model offers a large-animal platform for studying mtDNA mutations in aging and testing therapies.
A prespecified secondary analysis of the phase 3 VESALIUS-CV trial found that Repatha (evolocumab) added to standard statins or other LDL-C-lowering therapy reduced the risk of all-cause death by a significant 20% in more than 12,000 high-risk adults with no history of myocardial infarction or stroke. Amgen reports this makes Repatha the first and only PCSK9 inhibitor shown in a phase 3 trial to reduce all-cause death, including cardiovascular death, in high-risk primary prevention patients.
Pulmonary artery denervation (PADN) added to guideline-directed medical therapy (GDMT) reduced the risk of clinical worsening by 51% (HR 0.49, 95% CI 0.30-0.82; P=0.006) in patients with pulmonary hypertension due to left heart disease (PH-LHD). In the 264-patient, 25-center randomized PADN-HF-PH trial, presented at ESC 2026 and published in the New England Journal of Medicine, the combination also cut the annualized recurrence of clinical worsening events by 35.5% and lowered the risk of exercise-capacity decline by 63%, with a net 24.8-meter gain in six-minute walk distance. It is the first device randomized trial to show a positive primary endpoint in PH-LHD.
