Proven effective bleed protection and demonstrated safety
for patients with hemophilia with inhibitors1,2
Royal is a Novo Nordisk employee, has
hemophilia B with inhibitors, and uses Alhemo®
Royal is a Novo Nordisk employee, has hemophilia B with inhibitors, and uses Alhemo®
Study Design:
explorer7 was a multinational, multicenter, open-label, phase 3 trial that investigated the safety and efficacy of Alhemo® for routine prophylaxis in 91 adult (58 HAwI and 33 HBwI) and 42 adolescent (22 HAwI and 20 HBwI) patients who had been prescribed BPAs. Efficacy was evaluated when all patients in arms 1 and 2 had completed at least 24 or at least 32 weeks, respectively, by comparing the number of treated bleeding episodes between Alhemo® prophylaxis (arm 2) and no prophylaxis (arm 1).1
Primary Endpoint: The estimated mean ABR ratio was 0.14 (P<0.001)1
Treated spontaneous and traumatic bleeds1,2
IQR=interquartile range; PPx=prophylaxis.
64% (n=21) of Alhemo® patients experienced 24 bleed free weeks vs 10.5% on no prophylaxis (n=2)2
Supportive secondary endpoint, not alpha controlled.
Safety demonstrated in patients with inhibitors in the explorer7 study1
Adverse reactions reported in ≥5% HAwI and HBwI patients randomized to Alhemo® in explorer7
Adverse Reaction
Alhemo® Prophylaxis n=33 (%)
On-demand Treatment n=19 (%)
Injection site reactionsa
18%
0%
Urticariaa
6%
0%
Majority of injection site reactions were mild.2
Dosage interruptions of Alhemo® due to an adverse reaction occurred in 1 patient (3%) and was a hypersensitivity reaction.
aInjection 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.
The data described reflect exposure of 52 patients with HAwI and HBwI who were previously treated with 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.
Managing use of BPAs and surgeries1
No dose adjustment required
- For breakthrough bleeds
- For minor surgeries
Use the lowest approved dose for mild/moderate bleeds requiring treatment with BPAs (e.g., rFVIIa or aPCC).
- Maximum aPCC dose: 100 units/kg within 24 hours
For severe bleeds, follow the dosing instructions provided in the approved labeling for the specific product, based on clinical judgment.
Management of Alhemo® in major surgeriesb
It is generally recommended to pause Alhemo® at least 4 days prior to major surgery.
Therapy can be resumed 10 to 14 days after surgery with same maintenance dose without a loading dose while considering the overall clinical picture of the patient.
aDose and duration will depend on the location and severity of the bleed.
bThere is limited experience in the perioperative setting.
BPA=bypassing agent; aPCC=activated prothrombin complex concentrate; rFVIIa=recombinant activated factor VIIa.
Alhemo® offers individualized prophylaxis treatment for your hemophilia patients with inhibitors.
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Important Safety Information for Alhemo®
Contraindications
- Alhemo® is contraindicated in patients with a history of known serious hypersensitivity to Alhemo® or its components or the inactive ingredients
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 products or bypassing agents (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 (eg, atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, or septicemia).
Inform patients treated with Alhemo® 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
Indications and Usage
Alhemo® (concizumab-mtci) injection 60 mg, 150 mg, or 300 mg 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 and hemophilia B (congenital factor IX deficiency) with FIX inhibitors.
Important Safety Information cont'd
Warnings and Precautions cont'd
- 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 patients treated with Alhemo®. 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 most frequently reported adverse reactions (incidence ≥5%) were injection site reactions and urticaria
Drug Interactions
- Bypassing Agents: Take appropriate precautions when treating breakthrough bleeding events in hemophilia patients receiving Alhemo® prophylaxis and a bypassing agent. For mild and moderate bleeds that require additional treatment with bypassing agents (eg, 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 judgment.
An 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
Please click here for Alhemo® Prescribing Information.
References:
- Alhemo [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
- 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.