Novo Nordisk announced on April 20, 2026, that its Phase 3 HIBISCUS clinical trial for etavopivat successfully met both co-primary endpoints in patients with sickle cell disease (SCD). The topline results demonstrated that the once-daily oral treatment significantly reduced the frequency of vaso-occlusive crises (VOCs) and improved hemoglobin (Hb) response compared to a placebo.
The HIBISCUS trial was a randomized, double-blind, 52-week study involving 385 participants aged 12 and older. According to the data, patients treated with 400 mg of etavopivat experienced a 27% reduction in the annualized rate of VOCs. Furthermore, the treatment significantly prolonged the median time to a patient's first VOC to 38.4 weeks, compared to 20.9 weeks for those in the placebo group.
On the second co-primary endpoint, etavopivat showed a superior hemoglobin response. At week 24, 48.7% of participants in the treatment arm achieved a hemoglobin increase of greater than 1 g/dL from baseline. In contrast, only 7.2% of the placebo group reached this threshold, representing an adjusted rate difference of 41.2%. Exploratory analyses also indicated a reduced risk of blood transfusions for those on the therapy.
Etavopivat functions as a selective pyruvate kinase-R (PKR) activator. By activating this enzyme, the drug increases adenosine triphosphate (ATP) levels to improve red blood cell health and membrane stability. Simultaneously, it decreases 2,3-diphosphoglycerate (2,3-DPG) levels, which enhances hemoglobin-oxygen affinity and reduces the sickling of red blood cells.
Martin Holst Lange, Executive Vice President and Head of Research and Development at Novo Nordisk, stated that the results position etavopivat as a potential first-in-class therapy that could transform the lives of those with limited treatment options. Lange emphasized the company's commitment to advancing health equity and innovation within the sickle cell community.
The safety profile in the HIBISCUS trial was reported as well-tolerated and consistent with previous Phase 2 findings. Common adverse events included headache and nausea, with no new safety signals identified during the 52-week period.
Novo Nordisk acquired etavopivat through its $1.1 billion acquisition of Forma Therapeutics in 2022. This move was part of a strategic expansion into rare blood disorders, complementing the company's established presence in diabetes and obesity care. Following these positive results, Novo Nordisk plans to submit regulatory filings for etavopivat in the United States and Europe during the second half of 2026. The drug currently holds Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the U.S. Food and Drug Administration.