Novo Nordisk to present new data highlighting innovative rare blood disorders pipeline at ASH 2024

• Clinical data include analyses of novel, investigational therapies with the potential to help address unmet needs in sickle cell disease and hemophilia
• New data from the HIBISCUS phase 2 trial evaluating the efficacy and safety of etavopivat will be featured in ASH press briefing
• Key findings from one phase 3 trial evaluating the efficacy and safety of Mim8 prophylaxis and two phase 3 trials evaluating the impact of concizumab on hemophilia A and B with inhibitors supports Novo Nordisk's ongoing commitment to rare blood disorders

PLAINSBORO, N.J., Dec. 3, 2024 /PRNewswire/ -- Novo Nordisk today announced the presentation of 13 abstracts at the upcoming 66^th Annual Meeting and Exposition of the American Society of Hematology (ASH), which will take place from 7 to 10 December 2024 in San Diego, California.  

New results from the phase 2/3 HIBISCUS trial of investigational etavopivat in patients with sickle cell disease will be presented to determine the dose for the phase 3 part of the trial, as well as examine the safety and efficacy of etavopivat. This includes the incidence of vaso-occlusive crises, which occur when sickled red blood cells block blood flow, causing extreme pain. The HIBISCUS data will be highlighted in the ASH Annual Meeting Press Program session: Reading Up on the Classics: Treating Not-So-Benign Hematology Conditions on 7 December at 08:30 PST.

There are two oral presentations of note from Novo Nordisk's investigational hemophilia portfolio. The first explores the efficacy and safety results of an interim analysis from FRONTIER4, a phase 3 open-label, multi-center extension study of Mim8 in people living with hemophilia A with and without inhibitors (HA/HAwI). Additionally, new data from the phase 3 explorer7 study assesses the efficacy of concizumab in people with hemophilia A or B with inhibitors (HAwI/HBwI), with or without recurring bleeds into the same joint (or target joints) at baseline.

"There is a significant unmet need for novel treatment options that have the potential to transform care for people with rare blood disorders globally," said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. "I am particularly excited that we at the ASH congress will present new data from our pipeline in sickle cell disease, a first for Novo Nordisk. Sickle cell disease affects approximately eight million people worldwide with big consequences for the individual patient, yet there are few treatment options available. Our sickle cell research builds on our legacy in hemophilia, where we continue to advance research to address the unmet needs of patients."

Summary of presentations
Accepted data at the 66^th ASH annual meeting includes the following poster and oral presentations. Accepted abstracts include preliminary data that may be subject to change in final manuscripts which will be published in the journal Blood following the congress. Dates and times of the presentations can be found on the ASH website.

Sickle cell disease
Investigational etavopivat

• Etavopivat reduces incidence of vaso-occlusive crises in patients with sickle cell disease: HIBISCUS trial phase 2 results through 52 weeks (179-O)
• Etavopivat increases arterial hemoglobin-oxygen saturation during moderate and severe hypoxia: a mechanistic phase 1 trial in healthy volunteers (2461-P)

General sickle cell disease

• Large scale analysis of the real-world association between fetal hemoglobin and vaso-occlusive crises in sickle cell disease (1124-P)
• Characterizing people with sickle cell disease who share attitudes regarding clinical trial participation: findings from the global LISTEN survey (1135-P)
• How people with sickle cell disease rate motivators is associated with the likelihood of wanting to participate in a clinical trial: findings from the global LISTEN survey (1137-P)
• Motivators and barriers for people with sickle cell disease participating in clinical trials: United States findings from the LISTEN survey (1139-P)
• Noninvasive, accessible, smartphone app for at home hemoglobin monitoring in sickle cell disease (2248-P)

Hemophilia
Investigational Mim8

• Safety and efficacy of Mim8 prophylaxis administered once every two weeks for patients with hemophilia A with or without inhibitors: interim analysis of the FRONTIER4 open-label extension study (718-O)
• Mim8 prophylaxis beyond bleeding: investigating multifaceted, patient-reported outcomes for hemophilia A in the FRONTIER2 study (1212-P)

Investigational concizumab

• Annualized bleeding rates in patients with hemophilia A or B and inhibitors with and without target joints at baseline: results from the concizumab phase 3 explorer7 study (715-O)
• Unmet needs of patients with hemophilia A/B with or without inhibitors: real-world end-of-study results from the explorer6 non-interventional study (2585-P)

General hemophilia

• Burden of treatment on people with hemophilia: global real-world data (5077-P)
• Physical and psychological burden on people with hemophilia: global real-world data (2318-P)

About sickle cell disease
Sickle cell disease (SCD) is a debilitating, life-threatening group of rare, inherited red blood cell disorders, caused by a mutation in the hemoglobin gene.¹ This mutation causes red blood cells to become stiff and half-moon or 'sickle' shaped.¹ Sickle cells are less effective at carrying oxygen, don't last as long as healthy cells and risk getting stuck in blood vessels, leading to blockages known as vaso-occlusion.^2,3-7 Sickle cell disease is characterized by acute and chronic pain, anemia and fatigue alongside vaso-occlusive crises (VOCs), which can require hospitalization and can lead to complications including organ damage.^4,7 Globally, there are almost 8 million people living with sickle cell disease.⁸

About etavopivat
Etavopivat is an investigational, oral, small-molecule activator of erythrocyte pyruvate kinase (PKR) in development for the treatment of sickle cell disease and other hemoglobinopathies.⁹ Etavopivat-mediated activation of PKR lowers levels of 2,3 diphosphoglycerate (2,3 DPG) and raises adenosine triphosphate (ATP) levels, which has the potential to increase oxygen affinity, reduce hemolysis and decrease vaso-occlusive crises (VOCs).^9,10

About hemophilia
Hemophilia is a rare inherited bleeding disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding.¹¹ It is estimated to affect approximately 1,125,000 people worldwide.¹² There are different types of hemophilia, which are characterized by the type of clotting factor protein that is defective or missing.¹¹ Hemophilia A is caused by a missing or defective clotting Factor VIII (FVIII), and hemophilia B is caused by a missing or defective clotting Factor IX (FIX).¹¹ Hemophilia is often treated by replacing the missing clotting factor via intravenous infusions, also known as replacement therapy.¹³ However, sometimes the body can produce inhibitors as an immune response to the clotting factors in the therapy, which means replacement therapy does not work and limits overall treatment options.¹⁴

About Mim8
Mim8 is a FVIIIa mimetic bispecific antibody being investigated for once-weekly, once biweekly, and once-monthly prophylaxis for people living with hemophilia A, with and without inhibitors.¹⁵ Administered subcutaneously, Mim8 is designed to bridge Factor IXa/X (FIXa/FX) together upon activation, thereby replacing missing FVIII, which helps to restore thrombin generation capacity, and blood clotting.^15,16 The use of Mim8 in people living with HA/HAwI is investigational and not approved by any regulatory authority.

About concizumab
Concizumab is an investigational tissue factor pathway inhibitor (TFPI) antagonist designed to block a protein in the body that stops blood from clotting.¹⁷ By blocking TFPI, concizumab encourages the production of thrombin, which helps to clot the blood and prevent bleeding.¹⁷

About Novo Nordisk
Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 72,000 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com, Facebook, Instagram, X, LinkedIn, and YouTube.

Contacts for further information

References

1. American Society of Hematology. Sickle Cell Disease. Accessed November 2024. Available at: https://www.hematology.org/education/patients/anemia/sickle-cell-disease.
2. VCU Health. About sickle cell disease. Accessed November 2024. Available at https://www.vcuhealth.org/services/sickle-cell-program/about-sickle-cell-disease#:~:text=Sickle%20cell%20anemia%20is%20a,for%20days%20or%20even%20weeks. 
3. Safo MK, Kato GJ. Therapeutic strategies to alter the oxygen affinity of sickle hemoglobin. Hematol Oncol Clin North Am. 2014;28(2):217–231.
4. Jang T, Poplawska M, Cimpeanu E, et al. Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events. J Transl Med. 2021;19(1):397.
5. National Heart, Lung, and Blood Institute. What Is Sickle Cell Disease? Accessed November 2024. Available at https://www.nhlbi.nih.gov/health/sickle-cell-disease. 
6. Bailey M, Abioye A, Morgan G, et al. Relationship between vaso-occlusive crises and important complications in sickle cell disease patients. Blood. 2019; 134 (Supplement_1): 2167.
7. National Organization for Rare Disorders (NORD). Sickle cell disease. Rare Diseases. Accessed November 2024. Available at https://rarediseases.org/rare-diseases/sickle-cell-disease/.
8. Thomson, AM, et al. GBD 2021 Sickle Cell Disease Collaborators. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021. Lancet Haematol. 2023;10(8):e585–e599.
9. Saraf SL, Hagar R, Idowu M, et al. Multicenter, phase 1 study of etavopivat (FT-4202) treatment for up to 12 weeks in patients with sickle cell disease. Blood Adv. 2024;8(16):4459-4475. doi:10.1182/bloodadvances.2023012467.
10. Schroeder, P et al. Etavopivat for the treatment of sickle cell disease. J Pharmacol Exp. 2022; 380(3):210-219.
11. MedlinePlus. Hemophilia. Accessed: November 2024. Available at: https://medlineplus.gov/genetics/condition/hemophilia.
12. Iorio A, Stonebraker JS, Chambost H, et al; Data and demographics committee of the World Federation of Hemophilia. Establishing the prevalence and prevalence at birth of hemophilia in males: a meta-analytic approach using national registries. Ann Intern Med. 2019;171(8):540–546.
13. Centers for Disease Control and Prevention (CDC). Treatment of Hemophilia. Accessed: November 2024. Available at: https://www.cdc.gov/hemophilia/treatment/index.html.
14. Kim JY, You CW. The prevalence and risk factors of inhibitor development of FVIII in previously treated patients with hemophilia A. Blood Res. 2019 Sep;54(3):204-209. doi: 10.5045/br.2019.54.3.204.
15. Østergaard H, Lund J, Greisen PJ, et al. A factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice. Blood. 2021;138(14):1258-1268. doi:10.1182/blood.2020010331
16. U.S. National Library of Medicine. F8 gene. MedlinePlus Genetics. Accessed November 2024. Available at https://medlineplus.gov/genetics/gene/f8/ 
17. Matsushita T, Shapiro A, Abraham A, et al. Phase 3 Trial of concizumab in hemophilia with inhibitors. N Engl J Med. 2023;389:783–794.

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