Emicizumab

Emicizumab
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yashasvi Aryaputra[2], Anmol Pitliya, M.B.B.S. M.D.[3]

Disclaimer

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Black Box Warning

THROMBOTIC MICROANGIOPATHY AND THROMBOEMBOLISM See full prescribing information for complete Boxed Warning. *Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate was administered for 24 hours or more to patients receiving Emicizumab prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of Emicizumab if symptoms occur.

Overview

Emicizumab is a bispecific factor IXa- and factor X-directed antibody that is FDA approved for the prevention or reduction of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors. There is a Black Box Warning for this drug as shown here. Common adverse reactions include injection site reactions, headache, and arthralgia.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications:

• Emicizumab is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors.

Recommended Dosage:

• The recommended dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly.

Missed Dose

• If a dose of Emicizumab is not administered on the scheduled day, administer as soon as possible before the day of the next scheduled dose, and then resume usual weekly dosing schedule. Do not double doses to make up for a missed dose.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Emicizumab Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.

Non–Guideline-Supported Use

There is limited information regarding Emicizumab Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Indications:

• Emicizumab is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors.

Recommended Dosage:

• The recommended dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly.

Missed Dose

• If a dose of Emicizumab is not administered on the scheduled day, administer as soon as possible before the day of the next scheduled dose, and then resume usual weekly dosing schedule. Do not double doses to make up for a missed dose.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Emicizumab Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.

Non–Guideline-Supported Use

There is limited information regarding Emicizumab Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.

Contraindications

• None

Warnings

THROMBOTIC MICROANGIOPATHY AND THROMBOEMBOLISM See full prescribing information for complete Boxed Warning. *Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate was administered for 24 hours or more to patients receiving Emicizumab prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of Emicizumab if symptoms occur.

Thrombotic Microangiopathy Associated with Emicizumab and aPCC

• Cases of thrombotic microangiopathy (TMA) were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving Emicizumab prophylaxis. In clinical trials, thrombotic microangiopathy was reported in 1.6% of patients (3/189) and in 8.3% of patients (3/36) who received at least one dose of aPCC. Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity.

• Evidence of improvement was seen within one week following discontinuation of aPCC. One patient resumed Emicizumab following resolution of TMA.

• Consider the benefits and risks if aPCC must be used in a patient receiving Emicizumab prophylaxis. Monitor for the development of TMA when administering aPCC. Immediately discontinue aPCC and interrupt Emicizumab prophylaxis if clinical symptoms and/or laboratory findings consistent with TMA occur, and manage as clinically indicated. Consider the benefits and risks of resuming Emicizumab prophylaxis following complete resolution of TMA on a case-by-case basis.

Thromboembolism Associated with Emicizumab and aPCC

• Thrombotic events were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of aPCC was administered for 24 hours or more to patients receiving Emicizumab prophylaxis. In clinical trials, thrombotic events were reported in 1.1% of patients (2/189) and in 5.6% of patients (2/36) who received at least one dose of aPCC.

• No thrombotic event required anticoagulation therapy. Evidence of improvement or resolution was seen within one month following discontinuation of aPCC. One patient resumed Emicizumab following resolution of thrombotic event.

• Consider the benefits and risks if aPCC must be used in a patient receiving Emicizumab prophylaxis. Monitor for the development of thromboembolism when administering aPCC. Immediately discontinue aPCC and interrupt Emicizumab prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with thromboembolism occur, and manage as clinically indicated. Consider the benefits and risks of resuming Emicizumab prophylaxis following complete resolution of thrombotic events on a case-by-case basis.

Laboratory Coagulation Test Interference

• Emicizumab affects intrinsic pathway clotting-based laboratory tests, including activated clotting time (ACT), activated partial thromboplastin time (aPTT), and all assays based on aPTT, such as one-stage factor VIII (FVIII) activity (TABLE 1). Therefore, intrinsic pathway clotting-based laboratory test results in patients treated with Emicizumab should not be used to monitor Emicizumab activity, determine dosing for factor replacement or anti-coagulation, or measure FVIII inhibitor titers. Laboratory tests affected and unaffected by Emicizumab are shown in TABLE 1.

This image is provided by the National Library of Medicine.

Adverse Reactions

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 the clinical trials of another drug and may not reflect the rates observed in practice.

• The following adverse reactions are based on pooled data from a randomized trial (HAVEN 1), single-arm trial (HAVEN 2), and a dose-finding trial, in which a total of 189 male patients with hemophilia A received at least one dose of Emicizumab as routine prophylaxis. Ninety-four patients (50%) were adults (18 years and older), 38 (20%) were adolescents (12 years up to less than 18 years), 55 (29%) were children (2 years up to less than 12 years), and two (1%) were infants (1 month up to less than 2 years). Seven of the 189 patients (4%) included in the safety population were patients without FVIII inhibitors from the dose-finding trial. The median duration of exposure across the studies was 38 weeks (0.8 to 177.2 weeks).

• The most frequently reported adverse reactions observed in ≥ 10% of patients treated with at least one dose of Emicizumab were injection site reactions, headache, and arthralgia.

• Four patients (2.1%) in the clinical trials receiving Emicizumab prophylaxis withdrew from treatment due to adverse reactions, which were thrombotic microangiopathy, skin necrosis and superficial thrombophlebitis, and injection site reaction.

• Adverse reactions observed in patients who received Emicizumab are shown in TABLE 2.

This image is provided by the National Library of Medicine.

Characterization of aPCC treatment in pooled clinical trials

• There were 125 instances of aPCC treatment in 36 patients, of which 13 instances (10.4%) consisted of on average a cumulative amount of >100 U/kg/24 hours of aPCC for 24 hours or more; two of the 13 were associated with thrombotic events and three of the 13 were associated with TMA (TABLE 3). No TMA or thrombotic events were associated with the remaining instances of aPCC treatment.

This image is provided by the National Library of Medicine.

Injection Site Reactions

• In total, 35 patients (19%) reported injection site reactions (ISRs). All ISRs observed in Emicizumab clinical trials were reported as mild to moderate intensity and 88% resolved without treatment. The commonly reported ISR symptoms were injection site erythema (7.4%), injection site pruritus (5.3%), and injection site pain (5.3%).

Immunogenicity

• As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to Emicizumab-kxwh in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

• The immunogenicity of Emicizumab was evaluated using an enzyme-linked immunosorbent assay (ELISA) or an electrochemiluminescence (ECL) assay. No patients tested positive for anti-Emicizumab antibodies in HAVEN 1 and HAVEN 2 (n = 171). Four patients tested positive for anti-Emicizumab antibodies in the dose-finding trial (n = 18). The anti-Emicizumab antibody positive rate may be under-reported due to the limitation of the assay.

Postmarketing Experience

There is limited information regarding Emicizumab Postmarketing Experience in the drug label.

Drug Interactions

• Hypercoagulability with Concomitant Use of aPCC, rFVIIa, or FVIII
• Drug-Laboratory Test Interactions

Hypercoagulability with Concomitant Use of aPCC, rFVIIa, or FVIII

• Clinical experience suggests that a drug interaction exists with Emicizumab and aPCC.

• There is a possibility for hypercoagulability with rFVIIa or FVIII with Emicizumab based on preclinical experiments.

Drug-Laboratory Test Interactions

• Emicizumab restores the tenase cofactor activity of missing activated factor VIII (FVIIIa). Coagulation laboratory tests based on intrinsic clotting (i.e., aPTT) measure the total clotting time including time needed for activation of FVIII to FVIIIa by thrombin. Such intrinsic pathway-based tests will yield overly shortened clotting times with Emicizumab, which does not require activation by thrombin. The overly shortened intrinsic clotting time will then disturb all single-factor assays based on aPTT, such as the one-stage FVIII activity assay; however, single-factor assays utilizing chromogenic or immuno-based methods are unaffected by Emicizumab and may be used to monitor coagulation parameters during treatment, with specific considerations for FVIII chromogenic activity assays as described below.

• Chromogenic FVIII activity tests may be manufactured with either human or bovine coagulation proteins. Assays containing human coagulation factors are responsive to Emicizumab but may overestimate the clinical hemostatic potential of Emicizumab. In contrast, assays containing bovine coagulation factors are insensitive to Emicizumab (no activity measured) and can be used to monitor endogenous or infused FVIII activity, or to measure anti-FVIII inhibitors.

• Emicizumab remains active in the presence of inhibitors against FVIII, so it will produce a false-negative result in clotting-based Bethesda assays for functional inhibition of FVIII. Instead, a chromogenic Bethesda assay utilizing a bovine-based FVIII chromogenic test that is insensitive to Emicizumab may be used.

• Due to the long half-life of Emicizumab, effects on coagulation assays may persist for up to 6 months after the last dose.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Risk Summary

• There are no available data on Emicizumab use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies have not been conducted with Emicizumab-kxwh. It is not known whether Emicizumab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Emicizumab should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus.

• All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Emicizumab in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Emicizumab during labor and delivery.

Nursing Mothers

Risk Summary

• There is no information regarding the presence of Emicizumab-kxwh in human milk, the effects on the breastfed child, or the effects on milk production. Human IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Emicizumab and any potential adverse effects on the breastfed child from Emicizumab or from the underlying maternal condition.

Pediatric Use

• The safety and efficacy of Emicizumab have been established in pediatric patients. Use of Emicizumab in pediatric patients with hemophilia A with FVIII inhibitors is supported by a randomized trial (HAVEN 1) and a single-arm trial (HAVEN 2). HAVEN 1 included pediatric patients in the following age group: 38 adolescents (12 years to less than 18 years). HAVEN 2 included pediatric patients in the following age groups: 55 children (2 years up to less than 12 years) and two infants (1 month up to less than 2 years). No differences in efficacy were observed between the different age groups.

• In general, the adverse reactions in Emicizumab-treated pediatric patients were similar in type to those seen in adult patients with hemophilia A with FVIII inhibitors.

• The steady-state plasma trough concentrations of Emicizumab-kxwh were comparable in adult and pediatric patients at equivalent weight-based doses.

Geriatic Use

• Clinical studies of Emicizumab did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

Gender

There is no FDA guidance on the use of Emicizumab with respect to specific gender populations.

Race

There is no FDA guidance on the use of Emicizumab with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Emicizumab in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Emicizumab in patients with hepatic impairment.

Females of Reproductive Potential and Males

Contraception

• Women of childbearing potential should use contraception while receiving Emicizumab.

Immunocompromised Patients

There is no FDA guidance one the use of Emicizumab in patients who are immunocompromised.

Administration and Monitoring

Administration

Preparation and Administration

• Emicizumab is intended for use under the guidance of a healthcare provider. After proper training in subcutaneous injection technique, a patient may self-inject, or the patient's caregiver may administer Emicizumab, if a healthcare provider determines that it is appropriate. Self-administration is not recommended for children aged less than 7 years old. The Emicizumab "INSTRUCTIONS FOR USE" contains more detailed instructions on the preparation and administration of Emicizumab.

• Visually inspect Emicizumab for particulate matter and discoloration before administration. Emicizumab for subcutaneous administration is a colorless to slightly yellow solution. Do not use if particulate matter is visible or product is discolored.

• A syringe, a transfer needle, and an injection needle are needed to withdraw Emicizumab solution from the vial and inject it subcutaneously.

• Refer to the Emicizumab "INSTRUCTIONS FOR USE" for handling instructions when combining vials. Do not use different Emicizumab vials of different concentrations when combining vials to administer prescribed dose.

• Administer doses of Emicizumab up to 1 mL with a 1 mL syringe. A 1 mL syringe fulfilling the following criteria may be used: Transparent polypropylene or polycarbonate syringe with Luer-Lok™ tip, graduation 0.01 mL, sterile, for injection only, single-use, latex-free and non-pyrogenic, commercially available in the US.

• Administer doses of Emicizumab greater than 1 mL and up to 2 mL with a 2 mL or 3 mL syringe. A 2 mL or 3 mL syringe fulfilling the following criteria may be used: Transparent polypropylene or polycarbonate syringe with Luer-Lok™ tip, graduation 0.1 mL, sterile, for injection only, single-use, latex-free, and non-pyrogenic, commercially available in the US.

• A transfer needle fulfilling the following criteria may be used: Stainless steel needle with Luer-Lok™ connection, sterile, 18 gauge, length 1½ inch, semi-blunted tip, single-use, latex-free, and non-pyrogenic, commercially available in the US.

• An injection needle fulfilling the following criteria may be used: Stainless steel with Luer-Lok™ connection, sterile, 26 gauge, maximal length ½ inch, single-use, latex-free and non-pyrogenic, including needle safety feature, commercially available in the US.

• Administer each injection at a different anatomic location (upper outer arms, thighs, or any quadrant of abdomen) than the previous injection. An injection should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Administration of Emicizumab in the upper outer arm should only be performed by a caregiver or healthcare provider.

• Discard any unused Emicizumab remaining in the single-dose vial.

Monitoring

• Prevention or reduction of bleeding events in patients with hemophilia A may indicate efficacy.

• Extrinsic pathway clotting-based laboratory tests to determine Emicizumab-kxwh activity; determine dosing for factor replacement or anticoagulation, or measure FVIII inhibitor titers; do not use intrinsic pathway clotting-based laboratory test results, including activated clotting time (ACT), activated partial thromboplastin time (aPTT), and all assays based on aPTT such as one-stage factor VIII (FVIII) activity.

• Thrombotic microangiopathy and thrombotic events: In patients concomitantly receiving activated prothrombin complex concentrate.

IV Compatibility

There is limited information regarding the compatibility of Emicizumab and IV administrations.

Overdosage

There is limited information regarding Emicizumab overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Emicizumab?
Therapeutic monoclonal antibody
Source	zu
Target	Activated factor IX, factor X
Identifiers
CAS number	1610943-06-0
ATC code	B02BX06
PubChem	?
Chemical data
Formula	?
Mol. mass	?
Synonyms	ACE910
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	Template:Unicode Prescription only
Routes	Subcutaneous injection

Mechanism of Action

• Emicizumab bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective hemostasis.

Structure

There is limited information regarding Emicizumab Structure in the drug label.

Pharmacodynamics

There is limited information regarding Emicizumab Pharmacodynamics in the drug label.

Pharmacokinetics

• Emicizumab-kxwh exhibited dose-proportional pharmacokinetics over a dose range of 0.3 mg/kg (0.1 times approved recommended starting dosage) to 3 mg/kg once weekly following subcutaneous administration. Following multiple subcutaneous administrations of 3 mg/kg once weekly for the first 4 weeks in hemophilia A patients, mean (± SD) trough plasma concentrations of Emicizumab-kxwh increased to achieve 54.6 ± 14.3 μg/mL at Week 5. Trough plasma concentrations above 50 μg/mL were sustained thereafter with the recommended weekly dosage of 1.5 mg/kg; the mean (± SD) trough plasma concentrations of Emicizumab-kxwh at steady-state was 52.8 ± 13.5 µg/mL.

Absorption

• Following subcutaneous administration, the mean (± SD) absorption half-life was 1.7 ± 1 day.

• The absolute bioavailability following subcutaneous administration of 1 mg/kg was between 80.4% and 93.1%. Similar pharmacokinetic profiles were observed following subcutaneous administration in the abdomen, upper arm, and thigh.

Distribution

• The mean apparent volume of distribution was 11.4 L (95% confidence interval (CI) [10.6, 12.1]).

Elimination

• The mean apparent clearance (95% CI) was 0.24 L/day (0.22, 0.26) and the mean elimination apparent half-life (± SD) was 27.8 ± 8.1 days.

Specific Populations

• The pharmacokinetics of Emicizumab-kxwh are not influenced by age (3 years to 75 years), race (White 54%, Asian 30.5% and Black 8.5%), inhibitor status (inhibitor present, 92%), mild hepatic impairment (defined as total bilirubin 1× to ≤ 1.5× the upper limit of normal (ULN) and any aspartate transaminase (AST) level) and moderate hepatic impairment (defined as total bilirubin 1.5× to ≤ 3× the ULN and any AST level).

• Body weight: The apparent clearance and volume of distribution of Emicizumab-kxwh increased with increasing body weight (14.2 kg to 131 kg). Dosing in mg/kg provides similar Emicizumab-kxwh exposure across body weight range.

Drug Interaction Studies

• No drug-drug interaction studies have been conducted with Emicizumab.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• Studies in animals investigating the carcinogenic effects of Emicizumab-kxwh have not been conducted. In vitro and in vivo testing of Emicizumab-kxwh for genotoxicity was not conducted.

• Animal fertility studies have not been conducted; however, Emicizumab-kxwh did not cause any toxicological changes in the reproductive organs of male or female cynomolgus monkeys at doses of up to 30 mg/kg/week in subcutaneous general toxicity studies of up to 26-week duration and at doses of up to 100 mg/kg/week in a 4-week intravenous general toxicity study.

Clinical Studies

• The efficacy of Emicizumab for routine prophylaxis in patients with hemophilia A with FVIII inhibitors was evaluated in two clinical trials [an adult and adolescent study (HAVEN 1) and a pediatric study (HAVEN 2)].

HAVEN 1

• The HAVEN 1 study (NCT02622321) was a randomized, multicenter, open-label, clinical trial in 109 adult and adolescent males (aged 12 to 75 years and > 40 kg) with hemophilia A with FVIII inhibitors who previously received either episodic (on-demand) or prophylactic treatment with bypassing agents. Patients received weekly Emicizumab prophylaxis (Arms A, C, and D), 3 mg/kg once weekly for the first 4 weeks followed by 1.5 mg/kg once weekly thereafter, or no prophylaxis (Arm B). Dose up-titration to 3 mg/kg once weekly was allowed after 24 weeks on Emicizumab prophylaxis in case of suboptimal efficacy (i.e., ≥ 2 spontaneous and clinically significant bleeds). During the study, two patients underwent up-titration of their maintenance dose to 3 mg/kg once weekly.

• Fifty-three patients previously treated with episodic (on-demand) bypassing agents were randomized in a 2:1 ratio to receive Emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B), with stratification by prior 24-week bleed rate (< 9 or ≥ 9). Patients randomized to Arm B could switch to Emicizumab prophylaxis after completing at least 24 weeks without prophylaxis.

• Forty-nine patients previously treated with prophylactic bypassing agents were enrolled into Arm C to receive Emicizumab prophylaxis. Seven patients previously treated with episodic (on-demand) bypassing agents who had participated in a non-interventional study (NIS) prior to enrollment, but were unable to enroll into HAVEN 1 prior to the closure of Arms A and B, were enrolled into Arm D to receive Emicizumab prophylaxis.

• Efficacy was evaluated based on the annualized bleeding rate (ABR) requiring treatment with coagulation factors (minimum of 24 weeks or date of discontinuation) among patients previously treated with episodic bypassing agents who were randomized to Emicizumab prophylaxis (Arm A) compared with those receiving no prophylaxis (Arm B). The trial also evaluated the randomized comparison of Arms A and B for the efficacy of weekly Emicizumab prophylaxis in reducing the number of all bleeds, spontaneous bleeds, joint bleeds, and target joint bleeds, as well as patient-reported symptoms and physical functioning.

• The study also evaluated the efficacy of weekly Emicizumab prophylaxis compared with previous episodic (on-demand) and prophylactic bypassing agents in patients who had participated in the NIS prior to enrollment (Arms A and C, respectively). Only patients from the NIS were included in this comparison, because bleed and treatment data were collected with the same level of granularity in both periods.

• The efficacy results of Emicizumab prophylaxis compared with no prophylaxis in bleed rate for treated bleeds, all bleeds, treated spontaneous bleeds, treated joint bleeds and treated target joint bleeds are shown in TABLE 4.

This image is provided by the National Library of Medicine.

• In the intra-patient analysis, Emicizumab prophylaxis resulted in a statistically significant (p = 0.0003) reduction (79%) in bleed rate for treated bleeds compared with previous bypassing agent prophylaxis collected in the NIS prior to enrollment (TABLE 5).

This image is provided by the National Library of Medicine.

• The study evaluated patient-reported hemophilia-related symptoms (painful swellings and presence of joint pain) and physical functioning (pain with movement and difficulty walking far) using the Physical Health Score of the Haemophilia-specific Quality of Life (Haem-A-QoL) questionnaire for patients aged ≥ 18 years. The weekly Emicizumab prophylaxis arm (Arm A) showed an improvement compared with the no prophylaxis arm (Arm B) in the Haem-A-QoL Physical Health Subscale score at the Week 25 assessment (TABLE 6). The improvement in the Physical Health Score was further supported by the Total Score as measured by the Haem-A-QoL at Week 25.

This image is provided by the National Library of Medicine.

HAVEN 2

• The HAVEN 2 study (NCT02795767) was a single-arm, multicenter, open-label, clinical study in pediatric males (age < 12 years, or 12 – 17 years who weigh < 40 kg) with hemophilia A with FVIII inhibitors. Patients received Emicizumab prophylaxis at 3 mg/kg once weekly for the first 4 weeks followed by 1.5 mg/kg once weekly thereafter.

• The study evaluated the efficacy of weekly Emicizumab prophylaxis, including the efficacy of weekly Emicizumab prophylaxis compared with previous episodic (on-demand) and prophylactic bypassing agent treatment in patients who had participated in a non-interventional study (NIS) prior to enrollment (intra-patient analysis).

• At the time of the interim analysis, efficacy was evaluated in 23 pediatric patients who were < 12 years old and had been receiving weekly Emicizumab prophylaxis for at least 12 weeks, including 19 patients age 6 to < 12 years and 4 patients age 2 to < 6 years.

• Annualized bleed rate (ABR) and percent of patients with zero bleeds were calculated for 23 patients (TABLE 7). The median observation time for these patients was 38.1 weeks (12.7 – 41.6 weeks).

This image is provided by the National Library of Medicine.

• In the intra-patient analysis, 13 pediatric patients who had participated in the NIS had an ABR of 17.2 (95% CI [12.4, 23.8]) on previous bypassing agent treatment (prophylactic treatment in 12 patients and on-demand treatment for one patient). Weekly Emicizumab prophylaxis resulted in an ABR for treated bleeds of 0.2 (95% CI [0.1, 0.8]) based on negative binomial regression, corresponding to a 99% reduction in bleed rate. On Emicizumab prophylaxis, 11 patients (84.6%) had zero treated bleeds.

How Supplied

• Emicizumab (Emicizumab-kxwh) injection is available as a sterile, preservative-free, colorless to slightly yellow solution in single-dose vials in the following dosage strengths:

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Storage

• Store Emicizumab vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.

• Store Emicizumab vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.

• Prior to administration, if needed, unopened vials of Emicizumab may be stored out of and then returned to refrigeration. The temperature and total combined time out of refrigeration should not exceed 30°C (86°F) and 7 days (at a temperature below 30°C [86°F]), respectively.

• Once removed from the vial, discard Emicizumab if not used immediately.

• Discard any unused Emicizumab.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

Use of Bypassing Agents

• Inform the patient and/or caregiver that Emicizumab increases coagulation potential. Advise the patient and/or caregiver to discontinue prophylactic use of bypassing agents the day before starting Emicizumab prophylaxis. Discuss the use of bypassing agents with the patient and/or caregiver prior to starting Emicizumab prophylaxis.

Thrombotic Microangiopathy Associated with Emicizumab and aPCC

• Inform the patient and/or caregiver of the potential risk of thrombotic microangiopathy if aPCC is administered while receiving Emicizumab prophylaxis. Instruct the patient and/or caregiver to consult their healthcare provider if aPCC is required in cumulative doses exceeding 100 U/kg. Advise the patient and/or caregiver to seek immediate medical attention if any signs or symptoms of thrombotic microangiopathy occur.

Thromboembolism Associated with Emicizumab and aPCC

• Inform the patient and/or caregiver of the potential risk of thromboembolism if aPCC is administered while receiving Emicizumab prophylaxis. Instruct the patient and/or caregiver to consult their healthcare provider if aPCC is required in cumulative doses exceeding 100 U/kg. Advise the patient and/or caregiver to seek immediate medical attention if any signs or symptoms of thromboembolism occur.

Laboratory Coagulation Test Interference

• Inform the patient and/or caregiver that Emicizumab interferes with some laboratory tests that measure blood clotting and may cause a false reading. Advise the patient and/or caregiver that they should notify any healthcare provider about this possibility prior to any blood tests or medical procedures.

Instruction on Injection Technique

• Emicizumab is intended for use under the guidance of a healthcare provider. If a patient or caregiver is to administer subcutaneous Emicizumab, instruct him/her in injection techniques and assess his/her ability to inject subcutaneously to ensure proper administration of subcutaneous Emicizumab and the suitability for home use.

• Advise the patient to follow the recommendations in the FDA-approved patient labeling regarding proper sharps disposal.

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Precautions with Alcohol

Alcohol-Emicizumab interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

• Hemlibra

Look-Alike Drug Names

There is limited information regarding Emicizumab Look-Alike Drug Names in the drug label.

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.