A single subcutaneous dose of Kylo-11, a very long-acting small interfering RNA targeting lipoprotein(a), cut median serum lipoprotein(a) by up to -97% at 48 weeks in healthy adults with elevated concentrations, with reductions of -53% at 9 mg and -96% in participants above 200 nmol/L given 225 mg. In the 70 dosed participants, adverse events occurred in 53%, mostly grade 1-2 and deemed unrelated; there were no serious or drug-related events. The findings support durable lipoprotein(a) lowering from one dose.
Cytokinetics said on Friday that aficamten met both primary endpoints, symptom improvement and exercise capacity, in the pivotal ACACIA trial in non-obstructive hypertrophic cardiomyopathy (nHCM). The company plans to submit a marketing application to the FDA by the end of the year; if approved, it could become the first dedicated treatment for nHCM, though some experts consider the benefit limited.
Why it matters: Aficamten met both primary endpoints in an nHCM pivotal trial and could be the first approved drug for the indication, though some experts see limited benefit.
ICD implantation did not reduce the composite of sudden cardiac death or hemodynamically significant ventricular arrhythmia in patients with LVEF of 36% to 50% and CMR-defined myocardial scar. In the randomized trial of 353 patients followed for a median of 6.3 years, the composite occurred in 7.8% with an ICD vs 9.2% with an implantable loop recorder (HR 0.76; 95% CI, 0.37-1.58), though sudden cardiac death alone was lower with ICDs (1.7% vs 5.8%; HR 0.26). A scar-based selection strategy beyond the LVEF 35% cutoff did not change the primary outcome overall.
Aficamten, a cardiac myosin inhibitor, improved both exercise capacity and symptoms in symptomatic nonobstructive HCM, a condition with no previously proven medical therapy. In the phase 3 ACACIA-HCM trial, 258 patients received aficamten and 259 received placebo; at 36 weeks, peak oxygen uptake differed by a least-squares mean of 0.67 ml per kilogram per minute (P = 0.003) and KCCQ-CSS by 3.0 points (P = 0.02) in favor of aficamten. Reversible ejection fraction reductions below 50% occurred in 10.5% of aficamten patients versus 0.8% on placebo.
Upadacitinib 15 mg once daily produced clinically meaningful repigmentation in non-segmental vitiligo, a disease with no approved systemic therapies. In two phase 3 placebo-controlled trials, T-VASI 50 at week 48 was reached by 19% and 21% of patients on upadacitinib versus 6% on placebo in each study, and F-VASI 75 by 25% and 23% versus 6% and 7%; both coprimary endpoints met p<0·001. Safety was consistent with the known upadacitinib profile, with no new signals.
Once-weekly subcutaneous zenagamtide, a unimolecular GLP-1, amylin and calcitonin receptor agonist, lowered HbA1c in adults with type 2 diabetes on metformin with or without an SGLT2 inhibitor in a 36-week phase 2 dose-finding trial. Across doses of 0·4 to 40 mg, HbA1c fell from a baseline mean of 7·8% by up to -1·7%, with a treatment difference versus placebo of -1·56% at the highest dose (p<0·0001). Adverse events were mostly mild to moderate gastrointestinal effects; 21 of 261 exposed participants had serious adverse events and no deaths occurred.
Intravenous arginine did not shorten time to crisis resolution in sickle cell disease acute pain episodes in a phase 3 trial of 271 patients aged 3 to 21 across 10 US children's hospitals. Median time to crisis resolution was 60.8 hours with arginine vs 65.8 hours with placebo (absolute difference, 7.2 hours; 95% CI, -21.6 to 35.9 hours), and the trial was halted early for futility. Opioid use, pain scores, patient-reported outcomes, and safety events did not differ, overturning positive earlier phase 2 findings.
Akeso announced that its PD-1/VEGF bispecific antibody ivonescimab plus chemotherapy met the OS primary endpoint at an interim analysis assessed by the IDMC in the HARMONi-GI1 study in first-line advanced biliary tract cancer, and also met key secondary endpoints of PFS and ORR. The control arm was durvalumab plus chemotherapy, the guideline-recommended optimal first-line immunotherapy regimen. Akeso shares rose as much as 8.72% on the news.
Akeso's ivonescimab met the primary endpoint in a late-stage head-to-head trial in biliary tract cancer. On the news, Akeso shares rose as much as over 8% in morning trading, lifting its market value above HK$86.7 billion. Biliary tract cancer is a recognized refractory gastrointestinal tumor with limited first-line options; ivonescimab previously achieved a breakthrough in lung cancer, and this trial extends its scope. The report gives no trial name, hazard ratio, or confidence interval.
Why it matters: Ivonescimab met the primary endpoint in a head-to-head design where first-line biliary tract cancer options are limited, letting readers compare with existing data.
Sodium bicarbonate did not improve sustained return of spontaneous circulation in adults with in-hospital cardiac arrest. In this double-blind trial at 21 Danish hospitals, 372 patients given up to 100 mmol of sodium bicarbonate and 407 given placebo achieved sustained ROSC at similar rates (39% vs 37%; risk ratio 1.05, P = .62), with no significant differences in 30-day survival or favorable neurologic outcome. The findings do not support routine administration of sodium bicarbonate during in-hospital cardiac arrest, and alkalosis and hypernatremia were more common with it.
Sinobioway Seiton announced positive topline results from WS016CT301, the Phase III trial of its self-developed Class 1 polymer-based drug WS016 dry powder for suspension, in adult hyperkalemia in China. In Part A, both the primary endpoint and key secondary endpoints met the prespecified statistical criteria.
Why it matters: Phase III data for a domestic polymer potassium-lowering drug, with 24-hour reduction and over 60% of subjects restored to normal potassium, comparable to approved peers.
In August 2026, AstraZeneca announced it would discontinue eVOLVE-Lung02, a global Phase III study of the PD-1/CTLA-4 bispecific antibody Volrustomig plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer. In the primary analysis of the PD-L1 negative population, the regimen was unlikely to meet the dual primary endpoints of PFS and OS, and no new safety signals were found. The regimen was Volrustomig plus chemotherapy versus pembrolizumab plus chemotherapy head to head.
Why it matters: Reports negative results for Volrustomig plus chemotherapy versus pembrolizumab plus chemotherapy, a reference for same-target bispecifics in first-line NSCLC.
Intravenous deramiocel, a heart-derived cellular therapy, slowed disease progression in advanced Duchenne muscular dystrophy in the phase 3 HOPE-3 trial. Among 106 participants aged 10 years or older, total Performance of the Upper Limb 2.0 percentage change at 12 months significantly favoured deramiocel over placebo, with a safety profile similar to placebo. Quarterly outpatient infusions preserved skeletal muscle function regardless of the underlying genetic lesion.
Adjuvant nivolumab after upfront surgery did not improve disease-free survival in resected non-small cell lung cancer. Median disease-free survival was 71.3 months with nivolumab vs 68.8 months with observation (hazard ratio, 0.97; 1-sided P = .39), and the trial was stopped for futility. This contrasts with the established benefit of preoperative and perioperative nivolumab in this setting.
The Phase 3 randomized, double-blind INTerpath-001 trial of Moderna's personalized neoantigen vaccine intismeran plus pembrolizumab enrolled 1137 post-surgery high-risk patients, randomized 2:1 to intismeran 1 mg every 3 weeks plus pembrolizumab 400 mg every 6 weeks or pembrolizumab alone. Topline results were positive, with the effect size awaiting full unblinding.
Why it matters: First positive Phase 3 readout for a personalized neoantigen therapy, with enrollment size and combination regimen given as a benchmark for comparable pipelines.
In an updated phase III CARTITUDE-4 analysis, the BCMA-targeted CAR-T therapy cilta-cel continued to extend PFS over standard care in patients with lenalidomide-refractory relapsed/refractory multiple myeloma, and the OS difference crossed the prespecified statistical boundary at the second interim analysis. Results, with a median follow-up of 33.6 months, were published in The Lancet Oncology in January 2026.
Why it matters: The second interim OS analysis crossed the prespecified boundary, adding randomized OS evidence for BCMA CAR-T in lenalidomide-refractory multiple myeloma.
Adjuvant selpercatinib for up to 3 years after definitive therapy sharply reduced recurrence in RET fusion-positive NSCLC. In the 109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib versus 61% with placebo (hazard ratio 0.17; P<0.001), and blinded independent central review was consistent. The findings extend selpercatinib from advanced disease into the early-stage, curative-intent setting.
Moderna and Merck jointly announced that their personalized neoantigen mRNA vaccine for melanoma, intismeran autogene (mRNA-4157, V940), met both the primary endpoint of recurrence-free survival and the key secondary endpoint of distant metastasis-free survival in the Phase III INTerpath-001 trial. On the news, Moderna shares closed up 177% in one day, Merck rose more than 12%, and the Nasdaq Biotechnology Index climbed 6.39% to a record high.
Why it matters: Reports that the Phase III INTerpath-001 trial met both the RFS primary endpoint and the DMFS key secondary endpoint, a key benchmark for personalized mRNA cancer vaccine platforms.
Merck and Moderna jointly announced that the Phase III INTerpath-001 trial of intismeran autogene (V940/mRNA-4157) combined with KEYTRUDA (pembrolizumab) as adjuvant therapy for completely resected stage IIB-IV melanoma met both its primary endpoint of recurrence-free survival (RFS) and key secondary endpoint of distant metastasis-free survival (DMFS). The companies plan to present detailed data at an upcoming international medical conference.
Why it matters: INTerpath-001 met both RFS and DMFS in adjuvant melanoma, informing head-to-head comparison of individualized neoantigen mRNA therapy with PD-1 monotherapy adjuvant.
Once-daily oral zenagamtide, a unimolecular GLP-1, amylin and calcitonin receptor agonist, lowered HbA1c in adults with type 2 diabetes on metformin with or without an SGLT2 inhibitor. At week 36, estimated treatment differences versus placebo were -0·5% at 6 mg (p=0·033), -0·99% at 25 mg (p=0·0001), and -1·09% at 50 mg (p<0·0001). Gastrointestinal adverse events, the most common, rose with dose from 26% at 6 mg to 47% at 50 mg.
