FDA

Hemlibra

Approved 16 Nov 2017InjectionInjectable

The FDA lists this product in 4 strengths and forms.

Indications

HEMLIBRA is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors. HEMLIBRA is a bispecific factor IXa- and factor X-directed antibody indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors.

( 1 )

Contraindications

None. None ( 4 )

Warnings and precautions

Immunogenicity: Anti-emicizumab antibodies (including neutralizing antibodies) have developed in HEMLIBRA-treated patients. In case of clinical signs of loss of efficacy, promptly assess the etiology and consider a change in treatment if neutralizing antibodies are suspected. ( 5.3 , 12.6 , 14.3 ) Laboratory Coagulation Test Interference: HEMLIBRA interferes with activated clotting time (ACT), activated partial thromboplastin time (aPTT), and coagulation laboratory tests based on aPTT, including one-stage aPTT-based single-factor assays, aPTT-based Activated Protein C Resistance (APC-R), and Bethesda assays (clotting-based) for factor VIII (FVIII) inhibitor titers.

Intrinsic pathway clotting-based laboratory tests should not be used. ( 5.4 , 7.2 )

5.1Thrombotic Microangiopathy Associated with

HEMLIBRA 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 HEMLIBRA prophylaxis. In clinical trials, thrombotic microangiopathy was reported in 0.8% of patients (3/391) and in 8.1% of patients (3/37) 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 HEMLIBRA following resolution of TMA. Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Due to the long half-life of HEMLIBRA, the potential for an interaction with aPCC may persist for up to 6 months after the last dose.

At a glance

Brand name: Hemlibra
Active substance: emicizumab
Route: Injection
Dosage form: Injectable
Applicant: Genentech Inc
Status: Prescription
FDA approval: 16 Nov 2017
Application: BLA761083-003

Indications

( 1 )

Warnings and precautions

Intrinsic pathway clotting-based laboratory tests should not be used. ( 5.4 , 7.2 )

5.1Thrombotic Microangiopathy Associated with

Adverse reactions

The following serious adverse reactions are described elsewhere in the labeling: Thrombotic Microangiopathy Associated with HEMLIBRA and aPCC [see Warnings and Precautions (5.1) ] Thromboembolism Associated with HEMLIBRA and aPCC [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥ 10%) are injection site reactions, headache, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 two randomized trials in adult and adolescent patients (HAVEN 1 and HAVEN 3), one single-arm trial in adult and adolescent patients (HAVEN 4), one single-arm trial in pediatric patients (HAVEN 2), and one dose-finding trial, in which a total of 391 male patients with hemophilia A received at least one dose of HEMLIBRA as routine prophylaxis.

Two hundred eighty-one patients (72%) were adults (18 years and older), 50 (13%) were adolescents (12 years up to less than 18 years), 55 (14%) were children (2 years up to less than 12 years), and five (1%) were infants (1 month up to less than 2 years). The median duration of exposure across the studies was 34.1 weeks (0.1 to 224.4 weeks). The most frequently reported adverse reactions observed in ≥ 10% of patients treated with HEMLIBRA were injection site reactions, headache, and arthralgia.

Four patients (1%) in the clinical trials receiving HEMLIBRA prophylaxis withdrew from treatment due to adverse reactions, which were thrombotic microangiopathy, skin necrosis and superficial thrombophlebitis, headache, and injection site reaction. Adverse reactions observed in patients who received HEMLIBRA are shown in Table 2 . Table 2 Adverse Reactions Reported in ≥ 5% of Patients from Pooled Clinical Trials with HEMLIBRA Body System Adverse Reaction Number of Patients n (%) (N = 391) General Disorders and Administration Site Conditions Injection site reaction Includes injection site bruising, injection site discomfort, injection site erythema, injection site hematoma, injection site induration, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling, injection site urticaria, and injection site warmth. 85 (22%) Pyrexia 23 (6%) Nervous System Disorders Headache 57 (15%) Gastrointestinal Disorders Diarrhea 22 (6%) Musculoskeletal and Connective Tissue Disorders Arthralgia 59 (15%) Characterization of aPCC treatment in pooled clinical trials There were 130 instances of aPCC treatment in 37 patients, of which 13 instances (10%) 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. Table 3 Characterization of aPCC Treatment An instance of aPCC treatment is defined as all doses of aPCC received by a patient, for any reason, until there was a 36-hour treatment-free break. in Pooled Clinical Trials Duration of aPCC treatment Average cumulative amount of aPCC over 24 hours (U/kg/24 hours) < 50 50 – 100 > 100 < 24 hours 11 76 18 24 – 48 hours 0 6 3 Thrombotic event. > 48 hours 1 5 10 , Thrombotic microangiopathy. , , Injection Site Reactions In total, 85 patients (22%) reported injection site reactions (ISRs).

All ISRs observed in HEMLIBRA clinical trials were reported as mild to moderate intensity and 93% resolved without treatment. The commonly reported ISR symptoms were injection site erythema (11%), injection site pain (4%), and injection site pruritus (4%). Other Less Common (<1%) Reactions Rhabdomyolysis Rhabdomyolysis was reported in two adult patients with asymptomatic elevations in serum creatine kinase without associated renal or musculoskeletal symptoms.

In both instances, the event occurred following an increase in physical activity.

6.2Postmarketing Experience

The following adverse reactions have been identified during post-approval use of HEMLIBRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and subcutaneous tissue disorders : rash, urticaria, angioedema. Immune system disorders : hypersensitivity.

Hemlibra

Indications

Contraindications

Warnings and precautions

5.1Thrombotic Microangiopathy Associated with

At a glance

Two medicines in one question?

Hemlibra

Indications

Contraindications

Warnings and precautions

5.1Thrombotic Microangiopathy Associated with

At a glance

Two medicines in one question?

5.2Thromboembolism Associated with

5.3Immunogenicity Treatment with

5.4Laboratory Coagulation Test Interference

Interactions

7.1Hypercoagulability with Concomitant Use

7.2Drug-Laboratory Test Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information