Novo submits etavopivat, an investigational once-daily therapy for adolescents and adults living with sickle cell disease, to the FDA and EMA for approval

• The FDA New Drug Application (NDA) and EMA Marketing Authorization Application (MAA) submissions for etavopivat are based on data from the Phase 3 HIBISCUS trial showing efficacy and safety results in adolescents and adults living with sickle cell disease¹
• Sickle cell disease is a progressive, life-threatening, debilitating blood disease with limited disease-modifying therapeutic options that affects an estimated 100,000 Americans, 110,000 Europeans – and around 8 million people worldwide^2-4
• Etavopivat is designed to help reduce the sickling of red blood cells and is being evaluated for potential improvement of hemoglobin response (>1 g/dL) rate at week 24 and the reduction of annualized 'vaso-occlusive crises' (VOCs) rates at week 52¹

PLAINSBORO, N.J. and BAGSVÆRD, Denmark, Nov. 13, 2026 /PRNewswire/ -- Novo Nordisk today announced the submissions of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for etavopivat, an investigational, once-daily, orally available, selective activator of pyruvate kinase red blood cell isozyme (PKR), for the treatment of adolescents and adults (aged 12 years and older) living with sickle cell disease (SCD). If approved, etavopivat could offer a new approach to treating SCD as a disease-modifying therapy.

The FDA has previously granted etavopivat Fast Track, Rare Pediatric Disease and Orphan Drug designations and is expected to take action on the NDA in 2027. Etavopivat was also granted Orphan Drug designation by the European Commission who is expected to take action on the MAA in 2027. A MAA is the formal application for seeking approval to market a medicine in the European Union (EU).

"For people living with sickle cell disease, severe vaso-occlusive crises and other symptoms can have a profound impact on everyday life, and treatment options remain limited," said Martin Holst Lange, executive vice president, chief scientific officer and head of Research & Development at Novo. "If approved, we are hopeful that etavopivat can provide a new disease-modifying treatment option for people living with sickle cell disease, and we will continue to work alongside the community to help advance health equity and overcome the longstanding disparities that impact those affected by this disease."

The NDA and MAA submissions are grounded in the results from the HIBISCUS study program, which was designed to establish the efficacy and safety profile of etavopivat, and evaluated the annualized rate of vaso-occlusive crises (VOCs) at week 52 and hemoglobin response (>1 g/dL) rate at week 24 compared to placebo, in adults and adolescents living with SCD. Participants were also allowed to receive standard of care treatment throughout the trial.¹ In topline results announced in April 2026, etavopivat showed a 27% reduction in VOCs and a ~4-month delay to the first VOC compared to placebo. More detailed results from the HIBISCUS phase 3 trial will be presented at a future scientific conference and published in a peer-reviewed journal.

What is sickle cell disease?
Sickle cell disease (SCD) is driven by polymerization of mutated sickle hemoglobin (HbS) in red blood cells. The two main hallmarks of SCD are hemolytic anemia and vaso-occlusive crises (VOCs). Around 8 million people worldwide live with SCD, with the majority in low and middle-income countries.⁴ Approximately 100,000 people living with SCD are in the United States, as well as approximately 110,000 in Europe, 5.7 million in sub-Saharan Africa, 1.28 million in India, and 618,000 in the Middle East and North Africa.^3-5 The disease is characterized by several associated acute and chronic symptoms and complications such as acute chest syndrome, stroke and kidney, liver and heart disease.³ Despite recent advances in treatment, many people with SCD experience significant levels of pain and reduced lifespan by approximately 20 years compared to the general population.³

What is etavopivat?
Etavopivat is an investigational, once-daily, orally available, selective activator of pyruvate kinase red blood cell isozyme (PKR), a key enzyme in glycolysis. In SCD, PKR activation reduces 2,3-diphosphoglycerate (2,3-DPG) levels and increases adenosine triphosphate (ATP) production. Reduction of 2,3-DPG improves hemoglobin (Hb)-oxygen affinity, averting sickle hemoglobin polymerization and subsequent sickling. The increase in ATP production helps preserve RBC membrane integrity and deformability, improving RBC survival. These disease-modifying effects have the potential to reduce VOC events and improve Hb levels.

The US Food and Drug Administration 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.

Etavopivat was acquired by Novo as part of the 2022 acquisition of Forma Therapeutics.

What is the HIBISCUS program?
The HIBISCUS clinical development program investigates etavopivat as a disease-modifying treatment for people with SCD. The pivotal program includes:

HIBISCUS (NCT04624659) - a 52-week efficacy and safety design phase 2/3 trial, comparing once-daily etavopivat versus placebo, enrolling approximately 440 people aged 12 years and over with SCD who had 2 to 15 VOCs within 12 months prior to enrollment. Participants were allowed to receive standard of care treatment throughout the trial. Following the completion of the 12-week phase 2 interim readout, the phase 3 dose was selected, and participants were randomized to the phase 3 main phase of the trial, which continued for 52 weeks.¹

HIBISCUS 2 (NCT06612268) - a 52-week efficacy and safety phase 3b trial, comparing once-daily etavopivat versus placebo, with expected enrollment of 510 people aged 12 years and older with SCD.¹

FLORAL (NCT06609226) – an open-label extension following participation in etavopivat trials. The study allows the collection of long-term safety data.¹

Novo is the global healthcare company that believes lasting health starts now. For over a century, we've combined leading scientific expertise with a deep understanding of people's lives. We develop treatments and support that help millions of people make progress they can see, feel and sustain now and in the future. Every day, over 66,500 employees around the world advance our purpose to drive change for lasting health. Through our partnerships, programs and investments, we're working to prevent disease, expand access to treatments and reduce our environmental impact to help even more people live healthier lives. In the United States, Novo has a 40-year presence, is headquartered in New Jersey and employs approximately 10,000 people. For more information, visit novonordisk.com and novonordisk-us.com and follow us on Instagram, LinkedIn, TikTok, Facebook, X and YouTube.

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References

1. HIBISCUS Trial. Novo Nordisk Data on file. [Primary analysis of VOC based on negative binomial regression model with exposure time as offset variable. Primary analysis of Hb response based on exact Cochran-Mantel-Haenszel test with missing data ascribed as non-responders. Time to VOC based on Kaplan-Meier estimates and a stratified log-rank test.]
2. Belfer I, Chen W, Weber W, Edwards E, Langevin HM. Unmet need: mechanistic and translational studies of sickle cell disease pain as a whole-person health challenge. J Pain. 2024;25(10):104603. doi:10.1016/j.jpain.2024.104603 2. ASH sickle cell disease research priorities. American Society of Hematology. Accessed October 2026.
3. Centers for Disease Control and Prevention. Data and statistics on sickle cell disease. Sickle Cell Disease (SCD). Published May 15, 2024. Reviewed August 7, 2026. Accessed October 2026.
4. GBD 2021 Sickle Cell Disease Collaborators. 2023. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systemic analysis from the Global Burden of Disease Study 2021. The Lancet Haematology, 10, e585-e599. https://doi.org/10.1016/S2352-3026(23)00118-7
5. European Medicines Agency. EU/3/14/1263: Public summary of opinion on orphan designation. https://www.ema.europa.eu/en/documents/orphan-designation/eu3141263-public-summary-opinion-orphan-designation-autologous-cd34-haematopoietic-stem-cells-transduced-lentiviral-vector-encoding-human-beta-t87q-globin-gene-treatment-sickle-cell-dise_en.pdf. Accessed October 2026.

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SOURCE Novo Nordisk