Novartis' del-desiran (delpacibart etedesiran) missed the primary endpoint of video hand opening time (vHOT) versus placebo in the 150-patient Phase III HARBOR study in myotonic dystrophy type 1. The company reports evidence of activity in secondary and exploratory measures, including muscle strength and daily living activities, but has not disclosed numerical results or a presentation date. Four upcoming DMPK-targeting readouts will now test whether other candidates can translate molecular effects into clinical benefit.
Why it matters: The Phase III miss for the most advanced DMPK-targeting therapy leaves the mechanism's clinical translatability unresolved ahead of four readouts.
Adding atezolizumab to neoadjuvant taxane-carboplatin-anthracycline chemotherapy did not significantly improve event-free survival in stage II-III triple-negative breast cancer, with an HR of 0.80 (95% CI, 0.62-1.03; P = 0.083) and a 4-year EFS difference of 3.3%. Prespecified subgroup analysis suggested benefit in patients with clinical lymph node involvement (P interaction = 0.039), and an exploratory mRNA subset analysis pointed to basal-like immune-activated tumors as potential responders. Immune-related adverse events occurred in 27.6% with atezolizumab versus 11.4% with placebo.
A next-generation CD3×CD19 bispecific T cell engager given intravenously was well tolerated in patients with active systemic lupus erythematosus in a phase 1 trial, and most patients showed improvements in disease activity scores. The findings support further testing of B cell-directed T cell engagers in systemic lupus erythematosus.
Ivonescimab, from Akeso and Summit, cut the risk of death by 27% versus Keytruda in the phase 3 Harmoni-2 trial, which tested the drug as first-line treatment for PD-L1-positive non-small cell lung cancer. The survival benefit was especially pronounced in patients with high PD-L1 expression, strengthening the case for a challenger to pembrolizumab in this setting.
Tozorakimab is the first biologic to show statistically and clinically meaningful improvement in reducing moderate-to-severe exacerbations in a broad COPD population that still exacerbates despite standard inhaled therapy, based on full positive results from the OBERON and TITANIA trials. Clinical benefit was seen across blood eosinophil levels. Full results were published in the New England Journal of Medicine and reported at the European Respiratory Society annual congress.
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.
Inhaled siRNA directed against RAGE was safe and well tolerated in a first-in-human randomized trial, its first test in people after preclinical development. The lung-epithelium-targeted therapy reduced RAGE levels in both serum and bronchoalveolar lavage fluid, supporting gene silencing delivered by inhalation as a route to treating pulmonary inflammation.
AstraZeneca's injectable drug tozorakimab reduced COPD exacerbations by about 30% across all patients over a year in a pair of Phase 3 trials, with data presented at the European Respiratory Society conference and published in the New England Journal of Medicine. The trials included participants not eligible for other new COPD drugs, potentially giving the company a market segment to itself, with analysts projecting billions in annual sales if approved.
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.
A pivotal trial of Bristol Myers Squibb's GPRC5D-directed CAR-T cell therapy in multiple myeloma has met its primary endpoint. The result advances Bristol Myers Squibb's effort to compete with Johnson & Johnson for the post-BCMA multiple myeloma market. No outcome figures were disclosed in the announcement.
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.
Del-desiran, Novartis' experimental drug for myotonic dystrophy type 1, failed the Phase 3 HARBOR trial, missing its primary endpoint of outperforming placebo on video hand opening time (vHOT), a measure of the hand's ability to relax after squeezing. It is Novartis' second major trial failure within days, following a cardiovascular miss, and the stock fell as much as 10% in early Swiss trading, intensifying concern about the pipeline ahead of a patent cliff.
Novartis' del-desiran missed the primary endpoint in the phase 3 Harbor trial, undermining the centerpiece asset of its $12 billion acquisition of Avidity Biosciences. The readout gives Novartis one win and two failures across its recent run of key clinical trial results.
First-line osimertinib plus chemotherapy extended median progression-free survival to 34.0 months versus 15.6 months with osimertinib alone in treatment-naive advanced NSCLC patients with EGFR-sensitizing mutations and concurrent TP53 mutations, cutting the risk of progression or death by 56% (HR=0.44). The randomized phase 3 trial, led by researchers at Sun Yat-sen University Cancer Center and published in JAMA, is described as the first prospective trial dedicated to this co-mutated population, giving clinicians a biomarker-defined basis for adding chemotherapy to osimertinib.
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.
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.
Adding induction and consolidation atezolizumab to stereotactic body radiation therapy did not improve overall survival in patients with high-risk, inoperable, early-stage non-small-cell lung cancer in the SWOG/NRG S1914 phase 3 randomised trial. This was the first fully reported phase 3 cooperative group trial of immunotherapy in this setting, and the combination produced more grade 3 or higher adverse events than radiation alone. The results argue against adding atezolizumab to SBRT in this population.
