Phase 3 HIBISCUS: Etavopivat Cuts VOC Events, Improves Hemoglobin in SCD

Etovopivat showed a 27% reduction in vaso-occlusive crisis events and ~4-month delay to first vaso-occlusive crisis event on top of standard of care in patients with sickle cell disease, according to topline results from the phase 3 HIBISCUS trial.1

Novo Nordisk announced the results on April 20, 2026, with etabopivat meeting both co-primary endpoints, substantially reducing vaso-occlusive crisis events and improving haemoglobin response, 48.7% of people on treatment achieved an increase of >1g/dL after 24 weeks compared to 7.2% with placebo.1

“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,” said Martin Holst Lange, executive vice president, chief scientific officer and head of Research and Development at Novo Nordisk, in a company statement. “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.”

What is Etavopivat?

Etavopivat is an investigational, once-daily, orally bioavailable, selective Pyruvate kinase red blood cell (RBC) isozyme (PKR) activator. By activating PKR, it enhances glycolysis, leading to increased adenosine triphosphate (ATP) levels (improving RBC health/membrane stability) and decreased 2,3-diphosphoglycerate (2,3-DPG) levels, which increases hemoglobin-oxygen affinity and reduces sickle RBC sickling.1,2

Previously, in phase 2 HIBISCUS, etavopivat was well-tolerated in people with sickle cell disease and daily use resulted in improvements in vaso-occlusive crises, improvements in fatigue and hemolysis, and increases in hemoglobin levels compared to placebo.

In the randomized, double-blind phase 3 HIBISCUS trial, 400mg etavopivat was evaluated for efficacy and safety compared with placebo. The trial included 385 people ≥ 12 years of age with sickle cell disease.1,2

Further, as an exploratory analysis, etavopivat significantly reduced the risk of blood transfusion. Further, as an exploratory analysis, etavopivat significantly reduced the risk of blood transfusion.1

The US Food and Drug Administration (FDA) has granted etavopivat Fast Track, Rare Pediatric Disease and Orphan Drug designations. Additionally, etavopivat was granted Orphan Drug designation by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products of the European Medicines Agency for the treatment of patients with SCD.

In the second half of 2026, the company plans to submit for the first regulatory approval of etavopivat, while detailed results from HIBISCUS will be presented at a scientific conference in 2026.

References

1. Novo Nordisk A/S. Novo Nordisk: Etavopivat is the first in a new class of drugs to meet both co-primary endpoints in the phase 3 HIBISCUS trial, substantially reducing vaso-occlusive crisis events and improving haemoglobin response in sickle cell disease. GlobeNewswire News Room. Published April 20, 2026. Accessed April 20, 2026. https://www.globenewswire.com/news-release/2026/04/20/3276770/0/en/novo-nordisk-etavopivat-is-the-first-in-a-new-class-of-drugs-to-meet-both-co-primary-endpoints-in-the-phase-3-hibiscus-trial-substantially-reducing-vaso-occlusive-crisis-events-and.html

2. Wu G, Dhayakar P. Hibiscus 2 (Trial-in-Progress): A global, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of etavopivat in adolescents and adults with sickle cell disease. Blood. 2025;146(Supplement 1):2976-2976. doi:https://doi.org/10.1182/blood-2025-2976

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