Pelacarsen

Novartis said Tuesday a Phase III study evaluating delpacibart etedesiran (del-desiran) in people living with myotonic dystrophy type 1 (DM1) fell short on its key efficacy goal, with the company's shares down nearly 13% in premarket trading. Del-desiran was one of three antibody–oligonucleotide conjugate (AOC) therapies gained via the $12-billion buyout of Avidity Biosciences and had been touted as a potential blockbuster.The failure marks another setback for Novartis' pipeline, which has been hit by recent disappointment for pelacarsen in a late-stage cardiovascular outcomes trial and a temporary pause on early- and mid-stage studies of the CD19-directed CAR-T cell therapy rapcabtagene autoleucel due to patient deaths.The HARBOR study randomised approximately 150 individuals with DM1 to receive del-desiran or placebo every eight weeks. Del-desiran comprises a muscle-targeting anti-TfR1 monoclonal antibody linked to an siRNA designed to degrade toxic DMPK messenger RNA.Top-line results showed that the trial failed to meet its primary endpoint, with del-desiran failing to demonstrate a statistically significant improvement over placebo on video hand opening time (vHOT), a novel measure of hand myotonia. However, Novartis said that evidence of clinical activity was seen on secondary goals and exploratory analyses. The drugmaker said it will review the full dataset and engage with regulators on next steps."Developing therapies for a complex disease like DM1 remains challenging, and setbacks are part of scientific progress," said Shreeram Aradhye, chief medical officer of Novartis, adding that the company remains committed to "identifying the most appropriate development path for the del-desiran programme."Commenting on the news, Vontobel analyst Stefan Schneider said the failure of del-desiran — which Novartis CEO Vas Narasimhan recently forecast could generate $5 billion in peak sales — represents a "major pipeline setback" that "has not helped our confidence" in other therapies gained via the Avidity deal.The other two Avidity-sourced AOC candidates have shown promise in early and mid-stage testing. Last year, the Duchenne muscular dystrophy (DMD) hopeful delpacibart zotadirsen (del-zota) delivered 'unprecedented' functional benefits in the Phase I/II EXPLORE44 trial, prompting Novartis to seek accelerated FDA approval (.for more, see – KOL Views Q&A: Novartis’ neuromuscular splash — Avidity’s del-zota may redefine DMD exon-skipping). More recently, delpacibart braxlosiran (del-brax) met its primary and key secondary goals in a Phase II facioscapulohumeral muscular dystrophy study, supporting the dose selected for its ongoing late-stage trial.

iStock, Mohammed Haneefa Nizamudeen After the failure of Novo Nordisk’s IL-6 inhibitor ziltivekimab sent waves through the industry, the company has terminated two other studies of the asset, bringing the total number of high-pro flops to six over nine weeks. Novo Nordisk is ending two more late-stage studies for its investigational IL-6 inhibitor, citing expected futility and dimming prospects for the class as a whole in cardiovascular disease. The early discontinuations are for a pair of Phase 3 heart failure studies called HERMES and ATHENA , a spokesperson told BioSpace in a Tuesday email. The Danish pharma’s decision to shutter the studies early was “based on a recommendation from the Data Monitoring Committee on the totality of the data (including the low likelihood of a different outcome from ZEUS),” the spokesperson added. At the end of July, Novo’s IL-6 inhibitor ziltivekimab failed to reduce the risk of cardiovascular events in the late-stage ZEUS trial, dashing the pharma’s hopes for the heart inflammation program while also shaking other industry players working on the same pathway. “IL-6 now looks like an invalid target in chronic cardiovascular disease,” Oppenheimer analysts wrote on Tuesday. The industry had held out hope that the futility in ZEUS was potentially related to the trial’s population, which included patients with cardiovascular disease, chronic kidney disease and inflammation. Now, however, the futility terminations of both HERMES and ATHENA “remove the population-selection defense,” Oppenheimer said. HERMES enrolled nearly 5,000 patients with heart failure with mildly reduced ejection fraction and systemic inflammation, while ATHENA recruited 680 patients for the same type of heart failure. Immunology and inflammation Novo’s late-stage IL-6 stumble shakes inflammation space Novo Nordisk was banking on the inflammatory benefits of its investigational therapy ziltivekimab to improve cardiovascular outcomes. Last week’s Phase 3 failure dashed not just the Danish pharma’s hopes but that of other drugmakers working on the same pathway. August 3, 2026 · 2 min read · Tristan Manalac Read more With the addition of the two new trial fails, six total cardiovascular studies have flopped in just nine weeks, according to Oppenheimer. Beyond Novo’s three studies, AstraZeneca and Ionis Pharmaceuticals’ antisense oligonucleotide Wainua failed to significantly help patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), shaking the field’s confidence in the transthyretin silencer drug class. Most recently, Novartis’ antisense therapy pelacarsen showed no significant benefit on cardiovascular risk in a late-stage study. This outcome, analysts said, raises questions about a popular target for heart disease. When including Tenax Therapeutics’ late-stage flop for oral levosimendan in pulmonary hypertension due to heart failure with preserved ejection fraction, the findings have produced a narrative that cardiovascular outcome trials “are becoming unwinnable,” Oppenheimer said. But the analysts believe a deeper framing is needed, pointing to differences across the trials, such as attempts to treat different aspects of heart conditions and population variances. As for Novo, the obesity heavyweight is still waiting on results for another Phase 3 trial called ARTEMIS , which is testing ziltivekimab in the acute setting after heart attack. The study will continue as planned, with a readout slated for the first half of next year. “ARTEMIS remains active with lower expectations for success,” BMO analysts wrote Tuesday. The firm pointed to Novo’s Capital Markets Day, which will take place Sept. 21, as a near-term focus for investors. Novo’s stock has dipped 2% to $45.59 per share since market open on Tuesday. While Oppenheimer analysts were not entirely surprised about the new HERMES and ATHENA discontinuations, they did say they expect Novo shares “to be mildly pressured” by the announcement. Earnings Novo CEO sees innovation as a matter of survival amid pipeline setbacks Novo Nordisk CEO Maziar Mike Doustdar on a second quarter earnings call argued that failure is par for the course in the drug development business. The Danish pharma is focused on building out its pipeline to move past recent clinical roadblocks. August 5, 2026 · 3 min read · Tristan Manalac Read more