Results with CABLIVI^® (caplacizumab-yhdp)^1,2

The efficacy and safety of CABLIVI were established in one of the largest acquired/immune-mediated thrombotic thrombocytopenic purpura (aTTP/iTTP) clinical studies^1,2

HERCULES was a pivotal, phase 3, double-blind, randomized controlled trial of 145 patients with aTTP/iTTP assessing the efficacy and safety of CABLIVI in combination with PEX and immunosuppressive therapy.

*In combination with PEX and immunosuppressive therapy.
^†ISTH guidelines conditionally recommend CABLIVI in combination with PEX and immunosuppressive therapy. Conditional recommendation defined as desirable effects of following the recommendation probably outweighing the undesirable effects.^3
‡ISTH guidelines assume high likelihood of aTTP/iTTP based on clinical assessment or a formal clinical risk assessment tool (French or PLASMIC score) and timely access to ADAMTS13 (within 72 hours).³

Study design

Efficacy

In combination with PEX and immunosuppressive therapy,

CABLIVI helped to normalize platelet counts faster, reduced potentially serious aTTP/iTTP-related events, and had significantly fewer recurrences requiring reinitiation of PEX^1,2

Patients achieved normal platelet count significantly faster with CABLIVI^‖

The CABLIVI group (72)^†† reached platelet count normalization^‖ significantly faster than the PEX and immunosuppressive therapy group (73).

Time to platelet count response

CABLIVI significantly reduced potentially fatal and serious aTTP/iTTP-related events

Compared with PEX and immunosuppressive therapy alone (73), the CABLIVI group (72) demonstrated a significant reduction in a composite endpoint of aTTP/iTTP-related events (36 [49.3%] vs 9 [12.7%], respectively):

Total composite endpoint of aTTP/iTTP-related events during the study-drug period

Four aTTP/iTTP-related deaths occurred during the trial, including 1 non–treatment-related death in the CABLIVI group during the treatment-free follow-up period and 3 deaths in the placebo group during the treatment period.²

CABLIVI resulted in significantly fewer recurrences requiring reinitiation of PEX^§

Incidence of recurrences during treatment and throughout the 28-day follow-up post-treatment

^§Thrombocytopenia after initial recovery of platelet count (platelet count ≥150,000/μL) that required reinitiation of daily PEX was considered a recurrence. Recurrences were termed exacerbations if they occurred within 30 days of the last PEX and relapses if they occurred more than 30 days after the last PEX.^2
‖Platelet count normalization was defined as platelet count ≥150,000/μL with discontinuation of daily PEX 5 days thereafter.^2
††71 patients received at least 1 dose of study drug.

Healthcare resource utilization

In the HERCULES study, lower HRU was associated with early CABLIVI use vs placebo^2,4,5

These data were collected prospectively. Descriptive statistics were run but were not tested for significance. The clinical significance of these data is unknown.

To monetize the healthcare resource use outlines above, the 2019/20/21 MEDPAR file (100% sample) was used to obtain Medicare payments and charges for aTTP/iTTP cases with Medicare FFS coverage. The Medicare payment amount reflects the base DRG and outlier payments. A standard cost to charge ratio was applied to generate an estimated cost (ie, the cost to the hospital to deliver care) for ICU and non-ICU days—the latter factoring in patients who spend a portion of their time in the general ward and those who spend their entire stay in the general ward. The cost of PEX is based on Heatwole et al. Mean days in the ICU, cost per day: $2,702; mean days in the hospital, cost per day: $1,795–$2,193; mean days receiving PEX, cost per day: $4,597.

Safety

The safety of CABLIVI was established in 106 patients across 2 studies^1‡‡

Overall bleeding events

Severe bleeding was reported in 1% of patients for each of the following events:

Most frequent adverse reactions in phase 2 and phase 3 clinical studies¹

^‡‡Adverse reactions reported in ≥2% of patients treated with CABLIVI and that occurred more frequently than placebo during the blinded periods of the phase 2 and phase 3 studies.
^§§Urticaria was seen during PEX.

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.¹

Pediatric population

Efficacy of CABLIVI* was established in pediatric patients ≥12 years old with aTTP/iTTP¹

Study design: An observational, retrospective chart review was conducted to evaluate the efficacy of CABLIVI in 30 pediatric patients (≤18 years of age) diagnosed with aTTP. At the age of aTTP diagnosis, 21 patients (70%) were >12 years of age and 9 patients (30%) were ≤12 years old. The median study duration was 113 days (~3.7 months). Among the 30 patients, 29 received PEX for a median of 6 days after CABLIVI initiation. Major efficacy outcomes included clinical remission, time to platelet count response, refractory disease, and disease recurrence.¹

*In combination with PEX and immunosuppressive therapy.

CABLIVI is used in combination with PEX and immunosuppressive therapy to treat pediatric patients with aTTP/iTTP

^†1 kilogram=2.2 lb; 72.4 kg x 2.2 lb=159.3 lb.

Major efficacy outcomes^1*

*In combination with PEX and immunosuppressive therapy.
^†Proportion of patients achieving clinical remission, defined as platelet count remaining ≥150×10⁹/L and an LDH level <1.5×ULN for ≥30 days after cessation of TPE. 
^‡Time to platelet count response, defined as time from caplacizumab initiation to initial platelet count ≥150 x 10⁹/L with subsequent stop of daily TPE within 5 days. 
^§Proportion of patients with refractory iTTP, defined as lack of doubling of platelet count after 4 days of caplacizumab treatment and LDH level >ULN range.
^∥Proportion of patients with recurrent disease (aTTP exacerbation, defined as recurrence ≤30 days after last TPE, or relapse, defined as recurrence >30 days after last TPE).

The adverse reaction profile in pediatric patients ≥12 years was consistent with that in adults:

• The most commonly reported adverse events were epistaxis (n=4; 13.3%) and tachycardia (n=4; 13.3%)
• One serious bleeding adverse reaction was reported (hemorrhage urinary tract)

ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 13; CI=confidence interval; DRG=diagnosis-related group; FFS=fee for service; GI=gastrointestinal; HRU=healthcare resource utilization; ICU=intensive care unit; IS=immunosuppressive therapy; ISTH=International Society on Thrombosis and Haemostasis; PEX=plasma exchange; TE=thromboembolic; TTP=thrombotic thrombocytopenic purpura.