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-profile cardiovascular 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.
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.
