Brand Name
Cablivi
Generic Name
Caplacizumab
View Brand Information FDA approval date: February 06, 2019
Form: Kit
What is Cablivi (Caplacizumab)?
CABLIVI is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura , in combination with plasma exchange and immunosuppressive therapy. CABLIVI is a von Willebrand factor -directed antibody fragment indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura , in combination with plasma exchange and immunosuppressive therapy.
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Brand Information
Cablivi (caplacizumab)
1INDICATIONS AND USAGE
CABLIVI is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
2DOSAGE FORMS AND STRENGTHS
For injection: 11 mg as a white lyophilized powder in a single-dose vial.
3CONTRAINDICATIONS
CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of the excipients. Hypersensitivity reactions have included urticaria
4ADVERSE REACTIONS
The following clinically significant adverse reactions are also discussed in other sections of the labeling:
- Hemorrhage
4.1Clinical 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 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.
4.2Immunogenicity
As with all therapeutic proteins, there is 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 (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to caplacizumab-yhdp in the studies described below, with the incidence of antibodies in other studies, or to other products, may be misleading.
The prevalence of pre-existing antibodies binding to caplacizumab-yhdp observed during clinical studies and during evaluation of commercially available human samples varied between 4% and 63%. In aTTP patients, pre-existing antibodies can be produced by the patient or can originate from donor plasma during plasma exchange. No clinically apparent impact of these pre-existing antibodies on clinical efficacy or safety was found. Treatment-emergent anti-drug antibodies (TE ADA) against caplacizumab-yhdp were detected in 3% of patients treated with CABLIVI in the HERCULES study. In the HERCULES study, TE ADA were further characterized as having neutralizing potential. There was no clinically apparent impact on clinical efficacy or safety
4.3Postmarketing 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
5OVERDOSAGE
In case of overdose, based on the pharmacological action of CABLIVI, there is the potential for an increased risk of bleeding
6DESCRIPTION
Caplacizumab-yhdp is a von Willebrand factor (vWF)-directed antibody fragment that consists of two identical humanized building blocks, linked by a three-alanine linker. Caplacizumab-yhdp is produced in
CABLIVI (caplacizumab-yhdp) for injection is a sterile, white, preservative-free, lyophilized powder. Each single-dose vial delivers 11 mg caplacizumab-yhdp, anhydrous citric acid (0.18 mg), polysorbate 80 (0.10 mg), sucrose (62 mg), and trisodium citrate dihydrate (4.91 mg). After reconstitution with 1 mL of Sterile Water for Injection, USP, the final concentration is 11 mg/mL, at a pH of approximately 6.5.
7CLINICAL STUDIES
The efficacy of CABLIVI for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy was established in a pivotal multicenter, randomized, double-blind, placebo-controlled trial (HERCULES) (NCT02553317).
A total of 145 patients were enrolled in the HERCULES study; the median age was 45 (range: 18 to 79) years, 69% were female, 73% were White. Patients were randomized to either CABLIVI (n=72) or placebo (n=73). Patients in both groups received plasma exchange and immunosuppressive therapy. Patients were stratified according the severity of neurological involvement (Glasgow Coma Scale score ≤12 or 13 to 15). Patients with sepsis, infection with
Patients received a single 11 mg CABLIVI bolus intravenous injection or placebo prior to the first plasma exchange on study, followed by a daily subcutaneous injection of 11 mg CABLIVI or placebo after completion of plasma exchange, for the duration of the daily plasma exchange period and for 30 days thereafter. If after the initial treatment course, sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels remained present, treatment was extended for 7 day intervals for a maximum of 28 days.
The median treatment duration with CABLIVI was 35 days.
The clinical trial protocol specified the CABLIVI dose as 10 mg, to be delivered by withdrawing all of the reconstituted solution from the vial and administering the full amount. A dose recovery study showed that the mean dose that can be withdrawn from a vial is 11 mg. Therefore, based on the dose recovery study, the mean dose delivered in the trial was 11 mg.
The efficacy of CABLIVI in patients with aTTP was established based on time to platelet count response (platelet count ≥150,000/µL followed by cessation of daily plasma exchange within 5 days). Time to platelet count response was shorter among patients treated with CABLIVI, compared to placebo.
Figure 1: Platelet Response over Time
Treatment with CABLIVI resulted in a lower number of patients with TTP-related death, recurrence of TTP, or at least one treatment-emergent major thromboembolic event (a composite endpoint) during the treatment period (see
The proportion of patients with a recurrence of TTP in the overall study period (the drug treatment period plus the 28-day follow-up period after discontinuation of drug treatment) was lower in the CABLIVI group (9/72 patients [13%]) compared to the placebo group (28/73 patients [38%] (p<0.001). In the 6 patients in the CABLIVI group who experienced a recurrence of TTP during the follow-up period (i.e., a relapse defined as recurrent thrombocytopenia after initial recovery of platelet count (platelet count ≥150,000/µL) that required reinitiation of daily plasma exchange, occurring after the 30-day post daily plasma exchange period), ADAMTS13 activity levels were <10% at the end of the study drug treatment, indicating that the underlying immunological disease was still active at the time CABLIVI was stopped.
8PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Instructions for Use).
9PRINCIPAL DISPLAY PANEL - Kit Carton
NDC 58468-0225-1
Cablivi
For Intravenous and Subcutaneous Use
Must be reconstituted with diluent provided.
Single-dose vial. Discard unused portion.
Each carton contains:
- One 11 mg Cablivi single-dose vial
- One 1 mL Sterile Water for Injection, USP,
- One sterile vial adapter
- One sterile hypodermic needle (30 gauge)
- Two individually packaged alcohol swabs
11 mg
per vial
sanofi
