Novo Nordisk's semaglutide injection, Wegovy, has been approved in China for metabolic dysfunction-associated steatohepatitis (MASH), the first and only approval for this indication there. The decision rests on primary results from part 1 of the ESSENCE outcomes trial in semaglutide-treated MASH patients with moderate to severe hepatic fibrosis, which enrolled 1,197 patients with biopsy-confirmed MASH and F2 or F3 stage fibrosis. The approval extends the product's evidence base from weight management and cardiovascular health into liver health.
Impaired lactate processing in the liver drives lactic acidosis in skeletal muscle, and this emerges as a fundamental cause of sarcopenia in aged mice. Systemic lactate tolerance fell in aged mice, and lactic acidosis lowered nicotinamide adenine dinucleotide levels, disrupting skeletal muscle function. Pharmacological activation of hypoxia-inducible factor or liver-specific activation of HIF1α restored lactate tolerance, resolved muscle lactic acidosis, and improved sarcopenia.
Kura Oncology is spinning off its menin inhibitor programme into a new company, Caspian Therapeutics, which launches with $50 million in financing led by BVF Partners and joined by Eli Lilly. Animal studies of Kura's menin-targeting leukemia therapy showed the approach also helped control blood sugar, so Caspian will develop menin inhibitors for diabetes and other cardiometabolic diseases, taking its lead small molecule into an early-phase diabetes trial and backing a second candidate. Kura retains about 50% ownership, Kura CEO Troy Wilson becomes executive chair, and Robert Spencer was named to lead Caspian.
Mitiperstat, a myeloperoxidase inhibitor targeting the neutrophil–MPO inflammatory pathway, did not improve symptoms or exercise function in patients with heart failure with preserved or mildly reduced ejection fraction in a phase 2 randomized clinical trial. The finding argues against this anti-inflammatory approach as a symptomatic therapy in this population.
Caloric restriction reduces the accumulation of somatic mutations across the genome during aging in mice. Grońska-Pęski et al. measured mutation burdens genome-wide in mice under caloric restriction and found reduced mutation loads across several tissues and cell types. The work establishes that diet can alter genome-wide mutation accumulation during aging.
Pelacarsen, Novartis' antisense oligonucleotide targeting LPA, failed to improve cardiovascular outcomes in the Phase III HORIZON secondary prevention trial in patients with elevated Lp(a) levels. The miss undermines the company's first-in-class Lp(a) ambitions. Depending on the full data and on the fate of subsequent programs, the outcome could carry implications for antisense oligonucleotides, other RNA modalities and cardiovascular R&D more broadly.
Why it matters: A Phase III failure for the first-in-class Lp(a)-lowering antisense pelacarsen could reshape RNA-directed cardiovascular drug development.
Roivant's mosliciguat met all goals in a 16-week Phase 2 study in pulmonary hypertension, cutting pulmonary vascular resistance by a statistically significant 56% versus placebo. The drug also produced a 35-meter placebo-adjusted gain in six-minute walk distance and a 53% placebo-adjusted reduction in NT-proBNP, a blood marker of heart failure, supporting a new treatment approach for the lung disease.
Add-on tozorakimab, an interleukin-33 inhibitor, cut the annualized rate of moderate or severe COPD exacerbations by roughly 30% in two replicate phase 3 trials, OBERON and TITANIA, with no eosinophil-count eligibility criteria. Among former smokers, rates fell from 1.90 to 1.34 events per year (rate ratio 0.71) in OBERON and from 2.07 to 1.37 (rate ratio 0.66) in TITANIA. It offers a biologic option for exacerbation prevention independent of eosinophil status.
Novartis's pelacarsen lowered Lp(a) levels but failed to reduce cardiovascular event risk in a Phase III trial of 8323 patients that missed its primary endpoint. The miss forces the Lp(a) field, now a popular global drug development target, to confront whether lowering Lp(a) translates into cardiovascular benefit.
Novartis reported on September 4 that the Lp(a)HORIZON trial of pelacarsen missed its primary endpoint. The trial enrolled 8323 patients across 42 countries and was the first outcome trial designed to test whether lowering Lp(a) reduces cardiovascular events; Lp(a) fell, but cardiovascular events were not significantly reduced, despite earlier studies showing pelacarsen can lower Lp(a) by up to about 80%. The result forces a revaluation of the entire Lp(a)-lowering field, showing that lowering the lipid does not itself translate into fewer events.
The FDA has approved Eli Lilly's Mounjaro (tirzepatide) to reduce the risk of major adverse cardiovascular events (MACE-3), including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke, in adults with type 2 diabetes at high risk of cardiovascular events. The approval rests on the phase 3 SURPASS-CVOT trial, which showed Mounjaro was noninferior to active comparator Trulicity in reducing MACE-3 risk.
Novo Nordisk has halted two cardiovascular trials of ziltivekimab, the HERMES and ATHENA studies, after a data monitoring committee judged them unlikely to succeed. The decision follows the earlier failure of the same anti-inflammatory drug in the ZEUS trial, where it lowered markers of inflammation but did not reduce the risk of major clinical complications, including deaths and heart attacks. The stop is another setback for targeting inflammation to improve cardiovascular health.
The recombinant shingles vaccine was associated with a 9% decrease in cardiovascular burden over 7 years compared with the live attenuated vaccine (RMTL ratio = 0.91, 95% CI: 0.88-0.95) among US adults aged ≥60 years. Using the rapid transition between vaccines as a natural experiment, the study found reductions for ischemic heart disease (10%) and heart failure (12%) in both sexes, and ischemic stroke in males (12%). The authors say the results justify trials of potential cardioprotective effects.
Balanced crystalloid fluid did not improve outcomes over 0.9% saline in children with septic shock. In the PRoMPT BOLUS trial, conducted at 47 emergency departments in five countries, a major adverse kidney event occurred in 3.4% of the balanced-fluid group (137 of 4235 patients) versus 3.0% of the saline group (124 of 4247 patients) (risk ratio, 1.10; 95% CI, 0.88 to 1.40). Hyperchloremia was more frequent with saline, 49.0% versus 31.4%, without affecting the primary outcome.
In the double-blind, sham-controlled PVI-SHAM-AF trial, real catheter ablation was more effective than sham procedure at reducing atrial fibrillation recurrence, but at 6 months it did not provide a significant additional improvement in atrial fibrillation-specific quality of life over sham. Reported by Rolf Wachter at ESC 2026, the finding separates rhythm control from symptomatic benefit in a rigorously controlled design.
Inhaled mosliciguat, a soluble guanylate cyclase activator Roivant licensed from Bayer, hit the primary endpoint in the phase 2 PHocus trial: a placebo-adjusted 56.3% reduction in pulmonary vascular resistance at Week 16 among 135 patients with PH-ILD across 20 countries. Six-minute walk distance improved by 35.2 meters and NT-proBNP fell 53.2%, with cough in 12.1% of drug recipients versus 18.2% on placebo. Pulmovant has moved the once-daily therapy into phase 3.
A heat-wide association study of 916,904 acute-care visits among 372,140 adults across four Chicago health systems (2011 to 2023) identifies diagnoses linked to extreme heat beyond the usual restricted categories. After quasi-Poisson screening and case-crossover modeling, 33 clinically reportable diagnoses showed elevated cumulative odds over lags 0 to 3, including fluid-balance and renal disorders, dermatologic conditions, multiple sclerosis, and injuries. The full-diagnostic-spectrum approach broadens the clinical picture of heat-associated morbidity.
Pelacarsen, Novartis's antisense drug targeting Lp(a), significantly lowered Lp(a) but failed to translate that into reduced cardiovascular risk in a pivotal trial, the first to test whether lowering Lp(a) cuts cardiovascular risk. Novartis shares fell 5% after the news and Ionis fell 9%. The result clouds the most closely watched lipid target after PCSK9, where several small nucleic acid drugs and small molecules are in late-stage trials.
Novartis reported topline results from the Lp(a)HORIZON phase III trial of pelacarsen, an Lp(a)-targeting oligonucleotide therapy, in patients with elevated Lp(a) and established cardiovascular disease. Pelacarsen did not improve cardiovascular events compared with placebo. The result adds new evidence on the relationship between Lp(a) lowering and cardiovascular outcomes.
Fumarate covalently modifies SERCA2b at Cys875, inhibiting ER calcium uptake and disrupting calcium homeostasis. A Cys875Ser mutant resists fumarate-induced inhibition, and Drosophila knock-in flies carrying the corresponding mutation preserve ER calcium homeostasis and are protected from hyperglycemia, glucose intolerance, and reduced survival on a high-sugar diet. Pharmacological fumarate reduction or allosteric SERCA activation phenocopies these protective effects.
Why it matters: Identifies a specific covalent mechanism, SERCA2b Cys875 succination, linking glucose metabolism to calcium homeostasis and metabolic dysfunction.
