FDA approves Alhemo® injection as once-daily prophylactic treatment to prevent or reduce the frequency of bleeding episodes for adults and children 12 years of age and older with hemophilia A or B with inhibitors

News provided by

Dec 20, 2024, 19:27 ET

FDA approval is based on data from the pivotal phase 3 trial (explorer7) establishing the safety and efficacy of Alhemo^® for daily prevention of bleeds in adults and pediatric patients 12 years of age and older living with hemophilia A or B with inhibitors
Results from the pivotal trial showed an 86% reduction in treated spontaneous and traumatic bleeds in patients using Alhemo^®prophylaxis compared to no prophylaxis¹
This approval marks the first subcutaneous injection treatment of its kind for use in this patient population

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.^1,2Alhemo^® 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.^1,5In 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.⁹There 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.⁹However, 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.

It is not known if Alhemo^® is safe and effective in people receiving ongoing immune tolerance induction (ITI)
It is not known if Alhemo^® is safe and effective for hemophilia A and B with and without inhibitors in children younger than 12 years of age

Important Safety Information

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

It is important to follow the daily dosing schedule of Alhemo^® to stay protected against bleeding. This is especially important during the first 4 weeks of treatment to make sure a correct maintenance dose is established. Use Alhemo^® exactly as prescribed by your healthcare provider (HCP). Do not stop using Alhemo^® without talking to your HCP. If you miss doses, or stop using Alhemo^®, you may no longer be protected against bleeding
Your HCP may prescribe bypassing agents during treatment with Alhemo^®. Carefully follow your HCP's instructions regarding when to use on-demand bypassing agents, and the recommended dose and schedule for breakthrough bleeds

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:

Have a planned surgery. Your HCP may stop treatment with Alhemo^® before your surgery. Talk to your HCP about when to stop using Alhemo^® and when to start it again if you have a planned surgery.
Are pregnant or plan to become pregnant. It is not known if Alhemo^® may harm your unborn baby.

Females who are able to become pregnant

- Your HCP may do a pregnancy test before you start treatment with Alhemo^®.
- You should use an effective birth control (contraception) method during treatment with Alhemo^® and for 7 weeks after ending treatment. Talk to your HCP about birth control methods that you can use during this time
Are breastfeeding or plan to breastfeed. It is not known if Alhemo^® passes into your breast milk. Talk to your HCP about the best way to feed your baby during treatment with Alhemo^®

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^®?

Change (rotate) your injection site with each injection. Do not use the same site for each injection
To determine the right maintenance dose for you, your HCP will do a blood test to check the amount of Alhemo^® in your blood. Your HCP may do additional blood tests during treatment with Alhemo^®
Do not share your Alhemo^® pens and needles with another person, even if the needle has been changed. You may give another person an infection or get an infection from them
If you miss a dose of Alhemo^® during the first 4 weeks of treatment, contact your HCP right away. Your HCP will tell you how much Alhemo^® to inject

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

Blood clots (thromboembolic events). Alhemo^® may cause blood clots to form in blood vessels, such as in your arms, legs, heart, lung, brain, eyes, kidneys, or stomach. You may be at risk for getting blood clots during treatment with Alhemo^® if you use high or frequent doses of factor products or bypassing agents to treat breakthrough bleeds, or if you have certain conditions. Get medical help right away if you have any signs and symptoms of blood clots, including: swelling, warmth, pain, or redness of the skin; headache; trouble speaking or moving; eye pain or swelling; sudden pain in your stomach or lower back area; feeling short of breath or severe chest pain; confusion; numbness in your face; and problems with your vision
Allergic reactions. Alhemo^® can cause allergic reactions, including redness of the skin, rash, hives, itching, and stomach-area (abdominal) pain. Stop using Alhemo^® and get emergency medical help right away if you develop any signs or symptoms of a severe allergic reaction, including: itching on large areas of skin; trouble swallowing; wheezing; pale and cold skin; dizziness due to low blood pressure; redness or swelling of lips, tongue, face, or hands; shortness of breath; tightness of the chest; and fast heartbeat

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

Please click HERE for Alhemo® Prescribing Information and Medication Guide

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

Alhemo^® (concizumab-mtci) injection, for subcutaneous use [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
Hedner U. History of rFVIIa therapy. Thromb Res. 2010;125 Suppl 1:S4-S6. doi:10.1016/j.thromres.2010.01.021
Shapiro AD. Concizumab: a novel anti-TFPI therapeutic for hemophilia. Blood Adv. 2021;5(1):279
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
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.
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.
World Federation of Hemophilia. Annual Global Survey 2021. Accessed December 2024. Available at https://www1.wfh.org/publications/files/pdf-2399.pdf.
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.
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.
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.