Skip to main content

FDA Approves Alhemo

FDA Approves Alhemo (concizumab-mtci) to Prevent or Reduce Bleeding Episodes in People with Hemophilia A or B with Inhibitors

PLAINSBORO, N.J., Dec. 20, 2024 /PRNewswire/ -- Novo Nordisk announced today that the U.S. Food and Drug Administration (FDA) approved Alhemo (concizumab-mtci) injection as a once-daily prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or B with inhibitors, continuing its more than 35-year commitment to those living with rare bleeding disorders.1,2 Alhemo is a tissue factor pathway inhibitor (TFPI) antagonist that is dosed in a prefilled, premixed pen for subcutaneous injection (60 mg/1.5 mL, 150 mg/1.5 mL, or 300 mg/3 mL) via a thin 32 gauge, 4 mm needle, which is provided separately.1,3 Currently, many treatments for hemophilia A or B with inhibitors are administered via intravenous infusions, and Alhemo is the first subcutaneous injection treatment of its kind for this population.1,4,5

Alhemo is designed to block a protein called TFPI in the body that stops blood from clotting. By blocking TFPI, Alhemo improves the production of thrombin, a protein that helps to clot the blood and prevent bleeding, when the other clotting factors are missing or deficient in the presence of inhibitors.3,5

An estimated 30% of patients living with severe hemophilia A and 5-10% of those with severe hemophilia B develop inhibitors, which makes treatment of hemophilia in some patients significantly more challenging.4,6 While treatments have improved the lives of many living with hemophilia, those with hemophilia B with inhibitors still experience a disease and treatment burden due to limited prophylactic treatment options to prevent bleeding.4 Because of the unmet medical needs in this population, and based on the Phase 2 clinical trial results, the FDA granted Breakthrough Therapy designation for Alhemo in hemophilia B with inhibitors.3

"The approval of Alhemo signifies a remarkable achievement in prophylactic hemophilia treatment for individuals with inhibitors aged 12 years and older who, in some cases, currently have few options," said Anna Windle, SVP Clinical Development, Novo Nordisk. "As the first treatment of its kind for this population, Alhemo represents a significant step in helping to address the unmet needs of patients with hemophilia with inhibitors, highlighting Novo Nordisk's commitment to patient-centric innovations in rare diseases."

The primary objective from the pivotal Phase 3 explorer7 study compared the number of treated spontaneous and traumatic bleeding episodes, as measured by annual bleeding rate (ABR), showed an 86% reduction of ABR in patients randomized to receive Alhemo prophylaxis compared to no prophylaxis (ABR ratio of 0.14, 95% confidence interval [CI], 0.07 to 0.29, p-value <0.001). The estimated mean ABR was 1.7 for patients on Alhemo prophylaxis compared to 11.8 for patients with no prophylaxis and the overall median ABR was zero for treated spontaneous and traumatic bleeds compared with 9.8 ABR in patients with no prophylaxis.5 As a supportive secondary efficacy endpoint, 64% of the patients randomized to receive Alhemo prophylaxis treatment experienced zero treated spontaneous and traumatic bleeds during the first 24 weeks of treatment vs. 11% with no prophylaxis.5 In the explorer7 study, the most common adverse reactions reported in ≥5% of patients randomized to receive Alhemo were injection site reactions (18%) and urticaria (6%). Serious adverse reactions were renal infarct and hypersensitivity reaction.1

"The development of inhibitors remains the most serious treatment-related complication for people living with hemophilia. For patients with inhibitors, especially in hemophilia B, their hemophilia may remain poorly controlled and pose a life-threatening risk," said Amy Shapiro, MD, CEO and co-medical director at the Indiana Hemophilia & Thrombosis Center, Inc. "The approval of Alhemo – a first-of-its-kind, prophylaxis, subcutaneous injection pen for adults and children 12 years and older with hemophilia A and B with inhibitors – provides a much-needed alternative to the current standard of care in hemophilia B with inhibitors, while offering patients with hemophilia A with inhibitors more treatment options, ultimately providing more patients with inhibitors the opportunity to personalize their care and address current treatment gaps."

In addition to the U.S., Alhemo is currently approved in Australia, Japan, Switzerland and the EU, with specific indications varying by country.

About the explorer7 study
Explorer7 is a clinical trial that established the efficacy and safety of Alhemo for adults and pediatric patients 12 years of age and older living with hemophilia A or B with inhibitors.1,5 In explorer7, 52 males were randomly assigned in a 1:2 ratio to receive no prophylaxis (arm 1, n=19), or Alhemo prophylaxis (arm 2, n=33) and 81 males were nonrandomly assigned to receive Alhemo prophylaxis (arms 3 and 4).1,5 The initial loading dose of Alhemo was 1 mg per kilogram of body weight, followed by 0.2 mg per kilogram daily, and potentially individualized on the basis of concizumab-mtci plasma concentration as measured at week 4.1,5 The primary analysis was carried out when all patients in arms 1 and 2 completed at least 24 or 32 weeks, respectively, and compared the number of treated spontaneous and traumatic bleeding episodes, measured as ABR, between arms one and two.1,5 Supportive secondary endpoints, such as percent of patients experiencing zero bleeds, are reported as descriptive results only.5

About hemophilia with inhibitors
Hemophilia is a rare bleeding disorder that affects approximately 800,000 people worldwide and 32,000 people in the US, that impairs the body's ability to make blood clots, a process needed to stop bleeding.7-9 It is caused by a mutation in a gene that provides instructions for making the clotting factor proteins needed to form a blood clot.9 This change can prevent the clotting protein from working properly or be missing altogether.9 There are different types of hemophilia, which are characterized by the type of clotting factor protein that is defective or missing. Hemophilia A is caused by low levels of clotting factor VIII (FVIII), while hemophilia B is caused by low levels of clotting factor IX (FIX).9 Hemophilia is often treated by replacing the missing clotting factor via intravenous infusions, also known as replacement therapy.9 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.9,10

About Alhemo (concizumab-mtci) injection
Alhemo is a tissue factor pathway inhibitor (TFPI) antagonist, a protein in the body that helps to stop blood from clotting. By inhibiting TFPI, Alhemo enhances factor Xa (FXa) production during the initiation phase of coagulation, leading to improved thrombin generation and clot formation in patients with hemophilia A or B with inhibitors. The effect of Alhemo is not influenced by the presence of inhibitory antibodies to FVIII or FIX and Alhemo does not induce or enhance the development of direct inhibitors to FVIII or FIX. Alhemo is approved as a once-daily prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients 12 years of age and older with hemophilia A or B with inhibitors in the US.1

What is Alhemo?
Alhemo (concizumab-mtci) injection 60 mg, 150 mg, or 300 mg is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children 12 years of age and older with hemophilia A with factor VIII inhibitors or hemophilia B with factor IX inhibitors.

Important Safety Information

What is the most important information I should know about Alhemo?

Do not use Alhemo if you are allergic to concizumab-mtci or any of the ingredients in Alhemo.

Before using Alhemo, tell your HCP about all of your medical conditions, including if you:

Females who are able to become pregnant

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your HCP and pharmacist when you get a new medicine.

How should I use Alhemo?

What are the possible side effects of Alhemo?
Alhemo may cause serious side effects, including:

The most common side effects of Alhemo include: bruising, redness, bleeding, or itching at the site of injection, and hives.

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.

References

  1. Alhemo (concizumab-mtci) injection, for subcutaneous use [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
  2. Hedner U. History of rFVIIa therapy. Thromb Res. 2010;125 Suppl 1:S4-S6. doi:10.1016/j.thromres.2010.01.021
  3. Shapiro AD. Concizumab: a novel anti-TFPI therapeutic for hemophilia. Blood Adv. 2021;5(1):279
  4. Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition [published correction appears in Haemophilia. 2021 Jul;27(4):699]. Haemophilia. 2020;26 Suppl 6:1-158. doi:10.1111/hae.14046
  5. Matsushita T, Shapiro A, Abraham A, et al. Phase 3 trial of concizumab in hemophilia with inhibitors. N Engl J Med. 2023; 389(9): 783-794.
  6. Male C, Andersson NG, Rafowicz A, et al. Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study. Haematologica. 2021 106(1):123-129. doi: 10.3324/haematol.2019.239160. PMID: 31919092; PMCID: PMC7776246.
  7. World Federation of Hemophilia. Annual Global Survey 2021. Accessed December 2024. Available at https://www1.wfh.org/publications/files/pdf-2399.pdf.
  8. Centers for Disease Control and Prevention (CDC). Factor VIII and Factor IX. Accessed December 2024. Available at https://www.cdc.gov/hemophilia-community-counts/php/data-research/2024-march-factor-viii-and-factor-ix.html.
  9. Centers for Disease Control and Prevention (CDC). About Hemophilia. Accessed December 2024. Available at https://www.cdc.gov/hemophilia/about/?CDC_AAref_Val=https://www.cdc.gov/ncbddd/hemophilia/facts.html.
  10. 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.

SOURCE Novo Nordisk

Posted: December 2024

Alhemo (concizumab-mtci) FDA Approval History

More news resources

Subscribe to our newsletter

Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.