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.
Once-daily oral infigratinib (0.25 mg per kilogram) for 52 weeks increased annualized height velocity in children with achondroplasia by 1.74 cm per year versus placebo (P<0.001), with a height z score gain of 0.32 and no change in the upper-to-lower body segment ratio. In the 114-patient phase 3 trial, adverse events occurred in 96% of infigratinib recipients and 95% of placebo recipients, with no investigator-attributed drug-related serious events. It offers an oral treatment option targeting the FGFR3 pathway underlying achondroplasia.
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.
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.
Liver resection after response to atezolizumab plus bevacizumab prolonged time to treatment failure in advanced hepatocellular carcinoma with macrovascular invasion and no extrahepatic metastasis. In the phase 3 TALENTOP trial, 201 responders were randomised to surgery plus 12 months of the combination or maintenance therapy; median time to treatment failure was 20·4 versus 11·8 months (hazard ratio 0·60, p=0·015). Grade 3 or 4 treatment-related adverse events were more frequent with surgery (39% vs 21%).
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.
Ivonescimab, Akeso's PD-1/VEGF bispecific antibody, has beaten pembrolizumab on overall survival in the phase 3 HARMONi-2 trial, according to a company announcement on September 3. The predefined OS interim analysis passed review by the independent data monitoring committee, showing statistical significance and clinical benefit. Ivonescimab is the first bispecific antibody to outperform a PD-1 monoclonal antibody on OS in a phase 3 trial, in first-line PD-L1-positive (TPS ≥1%) locally advanced or metastatic NSCLC.
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.
Adding 177Lu-PSMA-617 to androgen deprivation therapy plus an androgen receptor pathway inhibitor reduced the relative risk of radiographic progression or death by 28% in PSMA-positive metastatic APMN/S prostate cancer, meeting the primary endpoint of prolonged radiographic progression-free survival. In the phase 3 PSMAddition trial, 572 patients per arm were randomised; radiographic progression or death occurred in 24% of the 177Lu-PSMA-617 arm versus 30% of the control arm. Grade 3 or worse adverse events occurred in 51% versus 43%, with dry mouth the most common event in the 177Lu-PSMA-617 arm.
Ivonescimab from Akesf outperformed pembrolizumab in the phase III HARMONi-2 head-to-head trial, meeting the primary endpoint of progression-free survival at interim analysis with a statistically significant result. Median PFS was 11.14 months with ivonescimab versus 5.82 months with pembrolizumab, hazard ratio 0.51. HARMONi-2 is the first phase III study to show a significant positive result against pembrolizumab.
Ivonescimab, the PD-1xVEGF bispecific from Akeso and Summit, has met its overall survival endpoint in a head-to-head trial against Keytruda. The result follows a progression-free survival win reported about two years ago, which had positioned the drug and its class as the leading candidate to replace Keytruda. The overall survival finding, however, has drawn a far more measured reception.
Etentamig, AbbVie's bispecific T-cell engager, improved response rates and progression-free survival in patients with relapsed/refractory multiple myeloma in a phase 3 trial. The positive data, released Thursday, support the candidate as a treatment option in this setting.
The YEARS algorithm was as safe as direct computed tomographic pulmonary angiography (CTPA) for ruling out acute pulmonary embolism in patients with active cancer. In the per-protocol analysis, 5 of 282 patients (1.8%) managed by YEARS vs 15 of 273 (5.5%) by CTPA only had symptomatic venous thromboembolism or possible PE-related death within 90 days (absolute risk difference, -3.7%; upper bound of 99.9% CI, 1.4%), and 22% of YEARS patients avoided CTPA entirely. This challenges guideline advice to send all cancer patients with suspected PE straight to CTPA.
Ultragenyx's phase 3 Aspire trial of apazunersen in Angelman syndrome missed its primary endpoint of change from baseline in Bayley-4 cognitive raw score and its secondary endpoint of net response on the Multidomain Responder Index. The company is reviewing the program's future and planning significant expense reductions. Shares fell 43% after hours; no trial figures were disclosed.
Ultragenyx reported that GTX-102, its experimental therapy for Angelman syndrome, showed no benefit versus sham treatment in a large Phase 3 trial. The drug had shown powerful results in early trials, raising hopes among families and advocates that it could pioneer medicines improving cognition and communication in intellectual disabilities. The failure also removes a drug investors counted on as Ultragenyx's path to profitability.
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.
