Novo Nordisk reports positive Phase 3 HIBISCUS trial results for etavopivat in sickle cell disease, showing reduced vaso-occlusive crises and improved haemoglobin response.
Written By: Dr. Anuja Badgujar, BDS
Reviewed By: Pharmacally Editorial Team
Novo Nordisk reported positive topline results from the pivotal Phase 3 HIBISCUS trial (NCT04624659) of etavopivat, an oral, once-daily therapy for sickle cell disease (SCD), demonstrating that the study met both co-primary endpoints with significant reductions in vaso-occlusive crises (VOCs) and improvements in haemoglobin (Hb) levels compared to placebo.
The randomized, double-blind, 52-week trial enrolled 385 patients aged 12 years and older, allowing standard of care treatment alongside etavopivat 400 mg or placebo. Patients receiving etavopivat showed a 27% reduction in annualized VOC rates and a prolonged median time to first VOC of 38.4 weeks versus 20.9 weeks for placebo.
The therapy also demonstrated a clinically meaningful haemoglobin response, with 48.7% of patients achieving an Hb increase greater than 1 g/dL at week 24 compared to 7.2% in the placebo group, alongside a reduced risk of blood transfusion in exploratory analyses. Etavopivat was generally well tolerated, with a safety profile consistent with previous studies.
Mechanism wise, etavopivat acts as a pyruvate kinase-R activator, improving red blood cell function by reducing 2,3-diphosphoglycerate levels and increasing ATP production, thereby enhancing haemoglobin oxygen affinity and limiting sickling.
Commenting on the results, Martin Holst Lange executive vice president, chief scientific officer and head of Research and Development at Novo Nordisk stated that the therapy has the potential to address a significant unmet need in SCD, a disease that severely affects patient quality of life and has limited treatment options, while reaffirming the company’s focus on improving access and advancing care globally.
Novo Nordisk plans to submit etavopivat for regulatory approval in the second half of 2026, with detailed trial data expected to be presented at a scientific conference the same year. The therapy has received Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the U.S. Food and Drug Administration, as well as Orphan Drug designation from the European Commission.
Sickle cell disease is a genetic blood disorder affecting around 8 million people worldwide and is associated with haemolytic anaemia, recurrent pain crises, organ damage, and a significantly reduced lifespan.
The HIBISCUS programme, which includes ongoing Phase 3 and extension studies, is designed to evaluate etavopivat as a potential disease-modifying therapy in this setting.
Notably, the clinical progress of etavopivat aligns with prior validation of the same mechanism class, as mitapivat, developed by Agios Pharmaceuticals, has already received approval from the U.S. Food and Drug Administration for the treatment of pyruvate kinase deficiency. While indicated for a different rare hemolytic anemia, mitapivat’s approval supports the therapeutic potential of pyruvate kinase-R activation in improving red blood cell function, thereby reinforcing the rationale for etavopivat’s development in sickle cell disease.
Reference
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, 20 April 2026, News Details
A Study of Etavopivat in Adults and Adolescents with Sickle Cell Disease (HIBISCUS) (HIBISCUS), ClinicalTrials.gov ID NCT04624659, ClinicalTrials.gov
About the Writer
Dr. Anuja Badgujar, BDS is a dentist with expertise in US healthcare data and medical data annotation. With four years of experience handling US healthcare datasets, she brings strong domain knowledge and precision to her work. She is also deeply passionate about medical writing, with a focus on translating complex medical information into clear and structured content.