Novo Nordisk has reported the mixed midphase results behind its push to enter a heart disease market served by Alnylam Pharmaceuticals, BridgeBio and Pfizer.
The phase 2 trial compared two doses of Novo’s coramitug to placebo in 104 people with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Coramitug, which Novo bought from Prothena for $100 million upfront in 2021, is designed to clear the TTR aggregates that drive the disease. The mechanism differentiates coramitug from existing drugs that stabilize native TTR or reduce synthesis of the protein.
Participants received infusions every four weeks. After 52 weeks, neither coramitug cohort performed better than the placebo arm on the six-minute walk test (6MWT), causing the trial to miss one of its two primary endpoints.
The other co-primary endpoint looked at changes in NT-proBNP, a biomarker for heart failure. Novo saw a statistically significant 48% reduction in the peptide in the high-dose cohort compared to the placebo arm. The drugmaker also linked the high dose of coramitug to improved functional echocardiographic parameters.
In a presentation at the American Heart Association’s (AHA's) 2025 Scientific Sessions, researchers said improvements in echocardiographic parameters suggested changes in the heart’s size and shape. Reversing detrimental changes to the organ can improve outcomes in heart failure patients.
Novo exited the phase 2 trial without evidence that improved functional echocardiographic parameters translate into clinical gains. But the AHA presenter said the failure on the 6MWT may reflect the small sample size and relatively short study duration. Those factors could have limited detection of significant changes.
Most participants received coramitug on top of an approved disease-modifying therapy. Tafamidis, which Pfizer sells as Vyndaqel and Vyndamax, was the main contaminant therapy, with 84% of patients taking the TTR stabilizer. A further 6% of patients were taking a TTR silencer from Alnylam.
Despite the mixed midphase data, Novo is working to establish coramitug as another option for ATTR-CM patients. The company committed to moving into phase 3 in August, one month after finishing the midstage trial. At that time, Novo aimed to start a phase 3 trial this year.