Phase 2 Study Shows Mixed Efficacy for Coramitug
Novo Nordisk has released results from a midstage study evaluating coramitug, its investigational therapy for transthyretin amyloidosis with cardiomyopathy (ATTR-CM), showing a mixed outcome in efficacy measures.
Trial Design and Endpoints
The phase 2 study included 104 participants diagnosed with ATTR-CM who received intravenous doses of coramitug or placebo every four weeks for a year. Coramitug, acquired by Novo Nordisk from Prothena in 2021 for $100 million upfront, is intended to remove the transthyretin (TTR) aggregates that cause the disease. This approach differs from currently available treatments that work by stabilizing native TTR or reducing its production.
The trial assessed two primary endpoints: the six-minute walk test (6MWT) and changes in NT-proBNP levels, a biomarker linked to heart failure. After 52 weeks, neither of the coramitug dose groups demonstrated improvement over placebo on the 6MWT, leading to a missed primary endpoint. However, the higher dose of coramitug showed a statistically significant 48% reduction in NT-proBNP levels compared with placebo, meeting the other primary endpoint.
Additional Findings and Context
Researchers also reported favorable trends in cardiac structure and function among patients receiving the higher dose. These changes, observed through echocardiographic measures, suggested potential reversal of harmful alterations in the heart’s size and shape. Novo Nordisk exited the phase 2 trial without evidence that these improvements translated into clinical gains.
At the American Heart Association’s 2025 Scientific Sessions, where the data were presented, investigators highlighted that the lack of improvement on the 6MWT might be linked to the limited sample size and relatively short follow-up period. The presenter stated that these factors may have reduced the study’s ability to capture significant differences between treatment groups.
Most participants were already receiving approved disease-modifying therapies for ATTR-CM in addition to the study drug. The majority, 84%, were taking tafamidis, Pfizer’s TTR stabilizer sold under the brand names Vyndaqel and Vyndamax. Another 6% of participants were on a TTR silencing therapy developed by Alnylam Pharmaceuticals.
Future Plans for Coramitug
Despite the mixed results, Novo Nordisk remains committed to advancing coramitug in ATTR-CM. The company announced in August that it would proceed to a phase 3 study following the completion of this phase 2 trial. Novo indicated plans to initiate the phase 3 program within the same year.
Commenting on the trial outcomes during the presentation, the AHA speaker noted, “The failure on the six-minute walk test may reflect the small sample size and relatively short study duration.” Novo Nordisk continues to evaluate the findings as it prepares for the next stage of clinical testing.
Coramitug works by clearing TTR aggregates instead of stabilizing or suppressing the protein. Novo Nordisk aims to expand treatment options for patients with ATTR-CM, a condition currently treated with therapies from Pfizer, Alnylam, and BridgeBio.
Additional Findings and Context
Researchers also reported favorable trends in cardiac structure and function among patients receiving the higher dose. These changes, observed through echocardiographic measures, suggested potential reversal of harmful alterations in the heart’s size and shape. Novo exited the Phase 2 trial without evidence that these improvements translated into clinical gains.
At the American Heart Association’s 2025 Scientific Sessions, where the data were presented, investigators highlighted that the lack of improvement on the 6MWT might be linked to the limited sample size and relatively short follow‑up period. The presenter stated that these factors may have reduced the study’s ability to capture significant differences between treatment groups.
Most participants were already receiving approved disease‑modifying therapies for ATTR‑CM in addition to the study drug. The majority, 84%, were taking Tafamidis (sold by Pfizer as Vyndaqel / Vyndamax). Another 6% of participants were on a TTR silencing therapy developed by Alnylam Pharmaceuticals.
