- 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.1,2 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.
- 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.
Further information
Media:
NNIMedia@novonordisk.com
Ambre James-Brown
+45
3079 9289
abmo@novonordisk.com
Liz Skrbkova (US)
+1 609 917 0632 (Mobile)
lzsk@novonordisk.com
Alhemo® is a registered trademark of
Novo Nordisk Health Care AG.
Novo Nordisk is a registered trademark of Novo Nordisk A/S.
© 2024 Novo Nordisk All rights reserved. US24AHM00077 December
2024
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