Concizumab
FDA Drug Information • Also known as: Alhemo
- Brand Names
- Alhemo
- Drug Class
- Tissue Factor Pathway Inhibitor Antagonist [EPC]
- Route
- SUBCUTANEOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Concizumab-mtci, is a humanized IgG4 monoclonal antibody produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells with an approximate molecular weight of 149 kDa. Alhemo (concizumab-mtci) injection is a clear to slightly opalescent, and colorless to slightly yellow solution that may contain translucent to white particles. Alhemo is supplied as a single-patient-use prefilled pen for subcutaneous injection. Each 1 mL of Alhemo single-patient-use prefilled pen (60 mg/1.5 mL) contains 40 mg active ingredient concizumab-mtci. Each 1 mL of Alhemo single-patient-use prefilled pen (150 mg/1.5 mL) contains 100 mg active ingredient concizumab-mtci. Each 1 mL of Alhemo single-patient-use prefilled pen (300 mg/3 mL) contains 100 mg active ingredient concizumab-mtci. Each 1 mL of Alhemo single-patient-use prefilled pen contains the following excipients: arginine hydrochloride (5.27 mg), histidine (5.12 mg), phenol (3.5 mg), polysorbate 80 (0.25 mg), sodium chloride (1.46 mg), sucrose (51.3 mg), and water for injection. Hydrochloric acid and sodium hydroxide may be added to adjust the pH to 6.0.
What Is Concizumab Used For?
1 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 or without FVIII inhibitors hemophilia B (congenital factor IX deficiency) with or without FIX inhibitors Alhemo is a tissue factor pathway inhibitor (TFPI) antagonist 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 or without FVIII inhibitors hemophilia B (congenital factor IX deficiency) with or without FIX inhibitors ( 1 )Dosage and Administration
2 DOSAGE AND ADMINISTRATION Administer Alhemo by subcutaneous injection to the abdomen or thigh with daily rotation of injection sites. ( 2.2 ) Recommended dosing regimen:
Day 1: Loading dose of 1 mg/kg Day 2: Once daily dose of 0.2 mg/kg until individualization of maintenance dose ( 2.1 ) o 4 weeks after initiation of treatment: For dose optimization, measure concizumab‑mtci plasma concentration by Concizumab Enzyme-Linked Immunosorbent Assay (ELISA) prior to administration of next scheduled dose using an FDA-authorized test for the measurement of concizumab-mtci concentration in plasma. See full Prescribing Information for important preparation and administration instructions and dosage adjustment. ( 2.1 , 2.3 , 2.4 ) 2.1 Recommended Dosage For subcutaneous use only. Alhemo should be administered once daily. Avoid missed doses. Recommended dosing regimen: Day 1: Loading dose of 1 mg/kg Day 2: Once daily dose of 0.2 mg/kg until individualization of maintenance dose (see below) 4 weeks after initiation of treatment: For dose optimization measure concizumab-mtci plasma concentration by Concizumab Enzyme-Linked Immunosorbent Assay (ELISA) prior to administration of next scheduled dose using an FDA-authorized test. Information on the FDA-authorized test for the measurement of concizumab-mtci plasma concentration is available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm. Once the concizumab-mtci concentration result is available, individualize the maintenance dose of Alhemo no later than 8 weeks after initiation of treatment, based on the following concizumab-mtci plasma concentrations: o Less than 200 ng/mL: adjust to a once daily dose of 0.25 mg/kg o 200 to 4,000 ng/mL: continue once daily dose of 0.2 mg/kg o Greater than 4,000 ng/mL: adjust to a once daily dose of 0.15 mg/kg The calculated dose is rounded off to the nearest injectable dose as follows: 60 mg/1.5 mL (40 mg/mL) in increments of 0.4 mg (brown label) 150 mg/1.5 mL (100 mg/mL) in increments of 1 mg (gold label) 300 mg/3 mL (100 mg/mL) in increments of 1 mg (white label) Additional measurements of concizumab-mtci plasma concentration should be taken at routine clinical follow-ups provided the patient has been on the same maintenance dose for 8 weeks of treatment to ensure steady state plasma concentration. Maintenance of concizumab plasma concentration above 200 ng/mL is important to decrease the risk of bleeding episodes. If concizumab-mtci plasma concentration remains below 200 ng/mL at two consecutive measurements, evaluate the benefits of continued Alhemo treatment versus the potential risk of bleeding events, and consider alternative therapies if available. As Alhemo is dosed by body weight (mg/kg), it is important to recalculate the dose when patients experience body weight changes. Missed Dose Adherence to daily dosing of Alhemo is important to maintain protection against bleeding. This is especially important during the initial 4 weeks...Side Effects (Adverse Reactions)
6 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 ( 5.1 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1.2 [see Warnings and Precautions ( 5.3 )] The most frequently reported adverse reactions (incidence ≥5%) were injection site reactions, headache and urticaria. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 [see Clinical Studies ( 14.1 )] . 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 Adverse Reaction Alhemo Prophylaxis N=33 (%) On-demand Treatment N=19 (%) 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. Patients with HA (hemophilia A without inhibitors) and HB (hemophilia B without inhibitors) The data described below reflect exposure of 63 patients with HA and HB who were previously treated on-demand therapy and who were randomized in explorer8 to arm 1 to receive on- demand treatment with factor product (n = 21) or arm 2 to receive Alhemo prophylaxis (n = 42) at the recommended dosing regimen [see Clinical Studies ( 14.2 )] . The median duration of treatment was 24.1 weeks (range 23.6, 56.1 weeks) in arm 1 (on- demand arm) and 32.1 weeks (range 3.9, 33.6 weeks) in arm 2 (Alhemo prophylaxis). The most common adverse reactions (≥5%) were injection site reactions and headache (see Table 2 ). Table 2. Adverse Reactions Reported in ≥5% HA and HB Patients Randomized to Alhemo in Explorer8 Adverse Reaction Alhemo Prophylaxis N=42 (%) On-demand Treatment N=21 (%) Injection site reactions 7% 0% Headache 7% 0% Injection site reactions included: injection site reaction, injection site rash, and...Drug Interactions
7 DRUG INTERACTIONS Breakthrough Bleeding Treatment: While treatment with all bypassing agents (e.g., rFVIIa or aPCC) can be used for breakthrough bleeds, high and/or frequent doses of FVIII, FIX, or bypassing agents with Alhemo increases the risk of thromboembolism. ( 7.1 ) 7.1 Breakthrough Bleeding Treatment Take appropriate precautions when treating breakthrough bleeding events in hemophilia patients receiving Alhemo prophylaxis and FVIII or FIX or a bypassing agent [see Dosage and Administration ( 2.1 )] . For mild and moderate bleeds that require additional treatment with FVIII or FIX or 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 [see Clinical Pharmacology ( 12.2 )] .
Contraindications
4 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 ( 5.1 )and Description ( 11 )]. Alhemo is contraindicated in patients with a history of known serious hypersensitivity to Alhemo or its components or the inactive ingredients. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on its mechanism of action, Alhemo may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Alhemo (concizumab-mtci) injection is a clear to slightly opalescent, colorless to slightly yellow liquid, that may contain translucent to white particles. Alhemo is available as one single-patient-use prefilled pen per carton in the following presentations (see Table 4 ): Table 4. Alhemo Presentations Presentation Label NDC Number 60 mg/1.5 mL (40 mg/mL) Brown 0169-2084-15 150 mg/1.5 mL (100 mg/mL) Gold 0169-2080-15 300 mg/3 mL (100 mg/mL) White 0169-2081-03 Storage and Handling Before first use: Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. Do not freeze. After first use: Store in a refrigerator at 36℉ to 46˚F (2℃ to 8˚C) or at room temperature below 86˚F (30˚C) for up to 28 days. Write the date of first use in the space provided on the carton. Discard the unused portion of the pen 28 days after first opening. Store Alhemo with the cap on and in the original carton to protect from light. Alhemo should not be stored in direct sunlight, and the Alhemo pen should be kept away from direct heat. Do not freeze or store it close to a cooling element in a refrigerator (the part that cools the refrigerator). Do not use Alhemo if it has been frozen or stored at temperatures above 86˚F (30˚C).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.