Distribution

Caplacizumab-yhdp central volume of distribution is 6.33 L in patients with aTTP.

Elimination

The half-life of caplacizumab-yhdp is concentration and target-level dependent.

Metabolism

The available data suggest target-bound caplacizumab-yhdp is metabolized within the liver.

Because caplacizumab-yhdp is a monoclonal antibody fragment, it is expected to be catabolizedby various proteolytic enzymes.

Excretion

The available nonclinical data suggest unbound caplacizumab-yhdp is cleared renally.

Antidrug Antibodies

No clinically significant differences in the pharmacokinetics of caplacizumab-yhdp wereobserved in patients with pre-existing or treatment-emergent anti-drug antibodies.

Specific PopulationsNo clinically significant differences in the pharmacokinetics of caplacizumab-yhdp wereobserved based on age (18 to 79 years), sex (66% females), race (White (83%) and Black (17%)), blood group (O (41%) and other groups (59%)), or renal impairment (mild [CrCl: 60 to

90 mL/min], moderate [CrCl: 30 to 60 mL/min] or severe [CrCl: 15 to 30 mL/min]). 

The effectof hepatic impairment on the pharmacokinetics of caplacizumab-yhdp is unknown [see Use in

Specific Populations (8.6)].

Drug Interaction Studies

No dedicated drug-drug interaction studies with caplacizumab-yhdp have been conducted.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been performed to eva luate the potential of caplacizumab-yhdp forcarcinogenicity or genotoxicity.

Animal reproduction studies assessing the effects of caplacizumab-yhdp on male and femalefertility have not been conducted.

14 CLINICAL STUDIES

The efficacy of CABLIVI for the treatment of adult patients with acquired thromboticthrombocytopenic purpura (aTTP) in combination with plasma exchange andimmunosuppressive 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: 18to 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 andimmunosuppressive therapy. Patients were stratified according the severity of neurological

involvement (Glasgow Coma Scale score ≤12 or 13 to 15). Patients with sepsis, infection with E.

coli 0157, atypical hemolytic uremic syndrome, disseminated intravascular coagulation orcongenital thrombotic thrombocytopenic purpura were not eligible for enrollment.

Patients received a single 11 mg CABLIVI bolus intravenous injection or placebo prior to thefirst 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 exchangeperiod 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, treatmentwas extended for 7 day intervals for a maximum of 28 days.

The median treatment duration with CABLIVI was 35 days.