AXS25 DigitalGuide V2 04.18 pages - Flipbook - Page 37
Alhemo ® (concizumab-mtci) injection
Rx Only
BRIEF SUMMARY: Please consult package insert
for full prescribing information.
INDICATIONS AND USAGE: Alhemo ® is indicated for
routine prophylaxis to prevent or reduce the frequency of
bleeding episodes in adult and pediatric patients 12 years
of age and older with: hemophilia A (congenital factor VIII
deficiency) with FVIII inhibitors; hemophilia B (congenital
factor IX deficiency) with FIX inhibitors
CONTRAINDICATIONS: Alhemo ® is contraindicated in
patients with a history of known serious hypersensitivity
to Alhemo ® or its components or the inactive ingredients
[see Warnings and Precautions].
WARNINGS AND PRECAUTIONS: Thromboembolic
Events: Venous and arterial thromboembolic events were
reported in 1.3% of patients (4/320) in Alhemo® clinical
trials. These cases occurred in patients with multiple risk
factors for thromboembolism, including the use of high doses
or prolonged treatment with factor product or bypassing
agent (2 of 4 events). Risk factors for thromboembolism may
include the use of high and/or frequent doses of breakthrough
bleed treatments (factor products or bypassing agents) or
conditions in which tissue factor is overexpressed (e.g.,
atherosclerotic disease, crush injury, cancer, disseminated
intravascular coagulation, thrombotic microangiopathy,
or septicemia). Inform Alhemo ® treated patients of signs
and symptoms of thromboembolic events. Monitor
patients for thromboembolic events. In case of suspicion
of thromboembolic events, discontinue Alhemo ® and
initiate further investigations and management strategies.
Hypersensitivity Reactions: Alhemo® is contraindicated
in patients with a history of known serious hypersensitivity
to Alhemo ® or its components or the inactive ingredients.
Hypersensitivity reactions including erythema, rash, pruritus,
and abdominal pain have occurred in Alhemo ® treated
patients. One patient (less than 1% of patients treated in the
clinical studies) experienced anaphylaxis which resolved
after treatment with antihistamines and corticosteroids.
Instruct patients of the signs of acute hypersensitivity
reactions. Instruct patients to contact their healthcare
provider for mild reactions and to seek urgent medical
attention for moderate to severe reactions. Discontinue
Alhemo ® if severe hypersensitivity symptoms occur, and
initiate medical management. Increased Laboratory
Values of Fibrin D-dimer and Prothrombin Fragment
1+2: Increased levels of fibrin D-dimer and increased levels
of prothrombin fragment 1.2 were seen in 29 (9.1%) and 18
(5.6%) of patients, respectively. The plasma concentration of
concizumab-mtci is positively correlated with fibrin D-dimer
and prothrombin fragments 1.2 indicating a hemostatic
effect of concizumab-mtci. For patients taking Alhemo ®,
these coagulation biomarkers may not be reliable predictive
markers for clinical decision-making with suspicion of
thrombosis such as deep vein thrombosis (DVT) and
pulmonary embolism (PE).
ADVERSE REACTIONS: The following clinically significant
adverse reactions are discussed in greater detail in other
sections of the labeling: Thromboembolic Events [see
Warnings and Precautions]; Hypersensitivity Reactions [see
Warnings and Precautions]; Increased Laboratory Values
of Fibrin D-dimer and Prothrombin Fragment 1+2 [see
Warnings and Precautions] Clinical Trials Experience:
Because clinical trials are conducted under widely varying
conditions, adverse reaction rates observed in the clinical
trials of a drug cannot be directly compared to rates in
clinical trials of another drug and may not reflect the rates
observed in clinical practice. The data in the WARNINGS
AND PRECAUTIONS reflect exposure to Alhemo® based
on pooled data from clinical trials explorer3 (phase 1b),
explorer4 (phase 2), explorer5 (phase 2), explorer7 (phase
3) and explorer8 (phase 3), in which a total of 320 male
patients with hemophilia A with and without inhibitors and
hemophilia B with and without inhibitors received at least
one dose of Alhemo ® as routine prophylaxis. The patients
were exposed for a total of 475 exposure years. Patients with
HAwI (hemophilia A with inhibitors) and HBwI (hemophilia B
with inhibitors): The data described below reflect exposure of
52 patients with HAwI and HBwI who were previously treated
on-demand therapy and who were randomized in explorer7
to arm 1 to receive on- demand treatment with bypassing
agents (n = 19) or arm 2 to receive Alhemo® prophylaxis
(n = 33) at the recommended dosing regimen. The median
duration of treatment was 31.1 weeks (range 3.9, 72.9 weeks)
in arm 1 (on- demand arm) and 40.1 weeks (range 3.1, 56.3
weeks) in arm 2 (Alhemo ® prophylaxis). Serious adverse
reactions were reported in 6.1% of patients who received
Alhemo®. These serious adverse reactions were renal infarct
and hypersensitivity reaction. Permanent discontinuation of
Alhemo ® due to an adverse reaction occurred in 1 patient
due to a renal infarct. Dosage interruptions of Alhemo ®
due to an adverse reaction occurred in 1 patient (3%)
and was a hypersensitivity reaction. The most common
adverse reactions (≥5%) were injection site reactions and
urticaria (see Table 1).
Table 1. Adverse Reactions Reported in ≥5%
HAwI and HBwI Patients Randomized to
Alhemo ® in Explorer7
Alhemo ® On-demand
Prophylaxis Treatment
Adverse Reaction
N=19
N=33
(%)
(%)
Injection site reactions
18%
0%
Urticaria
6%
0%
Injection site reactions included: Injection site bruising,
Injection site erythema, Injection site hematoma, Injection site
hemorrhage, Injection site reaction and Injection site urticaria.
Urticaria included: Urticaria and Injection site urticaria.
DRUG INTERACTIONS: Bypassing Agents: Take
appropriate precautions when treating break-through
bleeding events in hemophilia patients receiving Alhemo ®
prophylaxis and a bypassing agent. For mild and moderate
bleeds that require additional treatment with bypassing
agents (e.g., rFVIIa or aPCC), the lowest-approved dose
in the approved product labeling is recommended. For
aPCC, a maximum dose of 100 units/kg body weight within
24 hours is recommended. For severe bleeds, follow the
dosing instructions provided in the approved labeling for
the specific product based on clinical judgement. Additive
and sometimes synergistic increase in thrombin peak as
quantified in the thrombin generation assay has been
observed in plasma from hemophilia patients who were
on prophylactic treatment with concizumab-mtci with
concomitant presence of rFVIII, rFIX or bypassing agents
including rFVIIa and aPCC.
USE IN SPECIFIC POPULATIONS: Pregnancy: Risk
Summary: Based on its mechanism of action, Alhemo ®
may cause fetal harm when administered to a pregnant
woman. There are no available data on Alhemo ® use in
pregnant women to evaluate for a drug-associated risk of
major birth defects, miscarriage or other adverse maternal
or fetal outcomes. Animal reproduction studies have not
been conducted with Alhemo ®. Although there are no data
on concizumab-mtci, monoclonal antibodies can be actively
transported across the placenta, and concizumab-mtci may
cause fetal harm. It is unknown whether Alhemo® can affect
reproductive capacity. Alhemo® should only be used during
pregnancy if the potential benefit for the mother outweighs
the potential risk to the fetus. The estimated background risk
of birth defects and miscarriage for the indicated population
is unknown. All pregnancies have a background risk of birth
defect, loss, or other adverse outcomes. In the U.S. general
population, the estimated background risk of major birth
defect and miscarriage in clinically recognized pregnancies
is 2 to 4% and 15 to 20%, respectively. Lactation: Risk
Summary: There is no information regarding the presence
of Alhemo® in either human or animal milk, the effect on the
breastfed child, or the effects on milk production. Clinical
Considerations: Human IgGs are known to be excreted in
breast milk during the first few days after birth, decreasing
to low concentrations soon afterwards; consequently, a
risk to the breast-fed infant cannot be excluded during this
short period. Afterwards, Alhemo ® could be used during
breast-feeding if clinically needed. Females and Males of
Reproductive Potential: Pregnancy Testing: Pregnancy
testing is recommended for females of reproductive potential.
Contraception: Women of childbearing potential should use
a highly effective form of contraception during treatment
with Alhemo ® and for 7 weeks after ending treatment.
The benefits and thromboembolic risks of the type of
contraceptives used should be evaluated by the treating
physician. Pediatric Use: The safety and effectiveness
of Alhemo ® for hemophilia A and B with inhibitors have
been established in pediatric patients aged 12 years and
older. Use of Alhemo ® for this indication is supported by
evidence from adequate and well-controlled studies in adult
and pediatric patients aged 12 years and older [see Adverse
Reactions]. The safety and effectiveness of Alhemo ® for
hemophilia A and B with inhibitors have not been established
in pediatric patients younger than 12 years of age. Geriatric
Use: Clinical studies of Alhemo® did not include sufficient
numbers of patients 65 years of age and older to determine
whether they respond differently from younger adult patients.
Increased Body Weight: The apparent clearance and
volume of distribution of concizumab-mtci decreased with
increasing body weight. However, patients should receive
the approved recommended Alhemo ® dosage titration
and concizumab-mtci plasma concentration monitoring
regardless of body weight.
More detailed information is available upon
request.
For information about Alhemo ® contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536
1-844-668-6732
Manufactured by:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536
U.S. License No. 1261
At: Novo Nordisk A/S
Novo Allé 1
2880 Bagsvaerd
Denmark
PATENT INFORMATION: http://novonordisk-us.com/
products/product-patents.html
Alhemo® is a registered trademark of Novo Nordisk
Health Care AG.
Novo Nordisk® is a registered trademark of Novo Nordisk
A/S.
© 2025 Novo Nordisk
US24AHM00200 January 2025
