Cablivi
Generic: CAPLACIZUMAB
Basic Information
Manufacturer
Genzyme Corporation
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
FDA Set ID
2348f06e-8004-4040-832e-e9e86a39f905
Indications & Usage
1 INDICATIONS AND USAGE CABLIVI is indicated for the treatment of adult and pediatric patients 12 years of age and older with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
CABLIVI is a von Willebrand factor (vWF)-directed antibody fragment indicated for the treatment of adult and pediatric patients 12 years of age and older with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
( 1 )
CABLIVI is a von Willebrand factor (vWF)-directed antibody fragment indicated for the treatment of adult and pediatric patients 12 years of age and older with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are also discussed in other sections of the labeling: Hemorrhage [see Warnings and Precautions (5.1) ] In adults, the most common adverse reactions (incidence >15%) are epistaxis, headache, and gingival bleeding.
In pediatric patients, the most frequently reported adverse reactions are epistaxis and tachycardia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ablynx US at 1-800-745-4447 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 the clinical trials of another drug and may not reflect the rates observed in practice.
TITAN and HERCULES The safety of CABLIVI was evaluated in two placebo-controlled clinical studies (HERCULES, in which 71 patients received CABLIVI; and TITAN, in which 35 patients received CABLIVI).
The data described below and in the Warnings and Precautions reflect exposure to CABLIVI during the blinded periods of both studies, which include 106 patients with aTTP who received at least one dose, age 18 to 79 years, of whom 69% were female and 73% were White.
The median treatment duration with CABLIVI was 35 days (range 1–77 days).
The most frequently reported adverse reactions (>15%) were epistaxis, headache and gingival bleeding.
Seven patients (7%) in the CABLIVI group experienced an adverse reaction leading to study drug discontinuation.
None of the adverse reactions leading to discontinuation were observed in more than 1% of patients.
Among 106 patients treated with CABLIVI during the TITAN and HERCULES studies, serious bleeding adverse reactions reported in ≥2% patients included epistaxis (4%) and subarachnoid hemorrhage (2%).
Adverse reactions that occurred in ≥2% of patients treated with CABLIVI and more frequently than in those treated with placebo across the pooled data from the two trials are summarized in Table 1.
Urticaria was seen during plasma exchange.
Table 1: Adverse Reactions in ≥2% of Patients Treated with CABLIVI and More Frequent than Placebo During the Blinded Periods of aTTP Studies (HERCULES and TITAN) Adverse Reaction by Body System CABLIVI (N=106) n (%) Placebo (N=110) n (%) Gastrointestinal disorders Gingival bleeding 17 (16) 3 (3) Rectal hemorrhage 4 (4) 0 (0) Abdominal wall hematoma 3 (3) 1 (1) General disorders and administration site conditions Fatigue 16 (15) 10 (9) Pyrexia 14 (13) 12 (11) Injection site hemorrhage 6 (6) 1 (1) Catheter site hemorrhage 6 (6) 5 (5) Injection site pruritus 3 (3) 0 (0) Musculoskeletal and connective tissue disorders Back pain 7 (7) 4 (4) Myalgia 6 (6) 2 (2) Nervous system disorders Headache 22 (21) 15 (14) Paresthesia 13 (12) 11 (10) Renal and urinary disorders Urinary tract infection 6 (6) 4 (4) Hematuria 4 (4) 3 (3) Reproductive system and breast disorders Vaginal hemorrhage 5 (5) 2 (2) Menorrhagia 4 (4) 1 (1) Respiratory, thoracic and mediastinal disorders Epistaxis 31 (29) 6 (6) Dyspnea 10 (9) 5 (5) Skin and subcutaneous tissue disorders Urticaria 15 (14) 7 (6) Pediatric Patients The safety of CABLIVI in patients aged ≤18 years with aTTP was evaluated in an observational, retrospective chart review (OBS17325) [see Clinical Studies (14) ] .
The most commonly reported events were epistaxis in 4 (13.3%) patients and tachycardia in 4 (13.3%) patients.
One serious bleeding adverse reaction (hemorrhage urinary tract) was reported.
The adverse reaction profile in pediatric patients 12 years and older with aTTP was consistent with that in adults.
6.3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of CABLIVI.
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 caplacizumab-yhdp exposure.
General disorders and administration site conditions: Injection site reactions including injection site pain, injection site bruising and injection site erythema
In pediatric patients, the most frequently reported adverse reactions are epistaxis and tachycardia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ablynx US at 1-800-745-4447 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 the clinical trials of another drug and may not reflect the rates observed in practice.
TITAN and HERCULES The safety of CABLIVI was evaluated in two placebo-controlled clinical studies (HERCULES, in which 71 patients received CABLIVI; and TITAN, in which 35 patients received CABLIVI).
The data described below and in the Warnings and Precautions reflect exposure to CABLIVI during the blinded periods of both studies, which include 106 patients with aTTP who received at least one dose, age 18 to 79 years, of whom 69% were female and 73% were White.
The median treatment duration with CABLIVI was 35 days (range 1–77 days).
The most frequently reported adverse reactions (>15%) were epistaxis, headache and gingival bleeding.
Seven patients (7%) in the CABLIVI group experienced an adverse reaction leading to study drug discontinuation.
None of the adverse reactions leading to discontinuation were observed in more than 1% of patients.
Among 106 patients treated with CABLIVI during the TITAN and HERCULES studies, serious bleeding adverse reactions reported in ≥2% patients included epistaxis (4%) and subarachnoid hemorrhage (2%).
Adverse reactions that occurred in ≥2% of patients treated with CABLIVI and more frequently than in those treated with placebo across the pooled data from the two trials are summarized in Table 1.
Urticaria was seen during plasma exchange.
Table 1: Adverse Reactions in ≥2% of Patients Treated with CABLIVI and More Frequent than Placebo During the Blinded Periods of aTTP Studies (HERCULES and TITAN) Adverse Reaction by Body System CABLIVI (N=106) n (%) Placebo (N=110) n (%) Gastrointestinal disorders Gingival bleeding 17 (16) 3 (3) Rectal hemorrhage 4 (4) 0 (0) Abdominal wall hematoma 3 (3) 1 (1) General disorders and administration site conditions Fatigue 16 (15) 10 (9) Pyrexia 14 (13) 12 (11) Injection site hemorrhage 6 (6) 1 (1) Catheter site hemorrhage 6 (6) 5 (5) Injection site pruritus 3 (3) 0 (0) Musculoskeletal and connective tissue disorders Back pain 7 (7) 4 (4) Myalgia 6 (6) 2 (2) Nervous system disorders Headache 22 (21) 15 (14) Paresthesia 13 (12) 11 (10) Renal and urinary disorders Urinary tract infection 6 (6) 4 (4) Hematuria 4 (4) 3 (3) Reproductive system and breast disorders Vaginal hemorrhage 5 (5) 2 (2) Menorrhagia 4 (4) 1 (1) Respiratory, thoracic and mediastinal disorders Epistaxis 31 (29) 6 (6) Dyspnea 10 (9) 5 (5) Skin and subcutaneous tissue disorders Urticaria 15 (14) 7 (6) Pediatric Patients The safety of CABLIVI in patients aged ≤18 years with aTTP was evaluated in an observational, retrospective chart review (OBS17325) [see Clinical Studies (14) ] .
The most commonly reported events were epistaxis in 4 (13.3%) patients and tachycardia in 4 (13.3%) patients.
One serious bleeding adverse reaction (hemorrhage urinary tract) was reported.
The adverse reaction profile in pediatric patients 12 years and older with aTTP was consistent with that in adults.
6.3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of CABLIVI.
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 caplacizumab-yhdp exposure.
General disorders and administration site conditions: Injection site reactions including injection site pain, injection site bruising and injection site erythema