Novo Nordisk has recently announced positive topline results from its pivotal phase 3 HIBISCUS trial, evaluating the once daily oral PKR activator etavopivat. The trial, which included 385 adults and adolescents with sickle cell disease (SCD), successfully met both co-primary endpoints. The drug demonstrated a superior reduction in vaso-occlusive crises (VOCs) and a significantly improved hemoglobin (Hb) response compared to placebo.

Significant reduction in crises and improved survival of red cells

Etavopivat works by activating the pyruvate kinase-R enzyme, which helps increase energy production and improve the health and survival of red blood cells. In the HIBISCUS trial, patients treated with etavopivat experienced a 27% reduction in the annualized rate of VOCs. Additionally, the time to a patient’s first crisis was nearly doubled, extending from a median of 20.9 weeks in the placebo group to 38.4 weeks for those on etavopivat.

Hemoglobin response and transfusion benefits

The trial also showed a dramatic improvement in hemoglobin levels. Nearly half (48.7%) of participants on etavopivat achieved a hemoglobin increase of more than 1g/dL after 24 weeks of treatment, compared to just 7.2% of those receiving a placebo. Beyond these co-primary endpoints, exploratory analyses indicated that etavopivat significantly reduced the risk of patients needing blood transfusions.

Leadership perspective

Martin Holst Lange, executive vice president and head of R&D at Novo Nordisk, highlighted the potential for the new therapy:

“Sickle cell disease severely impacts the lives of millions of people. We are very excited that etavopivat has the potential to be a first and best-in-class therapy and transform the lives of people with sickle cell disease, who currently have limited therapeutic options. Novo Nordisk remains committed to collaborating with sickle cell disease communities around the world to drive innovation, advance health equity and improve access to treatment and care.”

Regulatory timeline and safety

Throughout the 52 week trial, etavopivat appeared to be well tolerated, with a safety profile consistent with earlier clinical studies. SCD affects approximately 8 million people globally, many of whom face life threatening complications and a significantly shortened lifespan. Based on these successful phase 3 results, Novo Nordisk plans to submit for the first regulatory approval of etavopivat in the second half of 2026.