The oral second-generation thrombopoietin‒receptor agonist avatrombopag (AVA) is in late-stage clinical testing for the treatment of chronic immune thrombocytopenia (ITP). The current multicenter, randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy and safety of AVA versus placebo for the treatment of patients with chronic ITP.
Eligible adult patients (age ≥18 years) had a diagnosis of chronic ITP for ≥12 months, defined by a baseline platelet count of <30 × 109/L, and previous treatment with ≥1 ITP therapies. Patients were randomized 2:1 to receive AVA 20 mg/day or placebo for 6 months. The primary efficacy end point was the number of cumulative weeks with a platelet response defined as a platelet count ≥50 × 109/L, in the absence of rescue therapy. Secondary end points included platelet response at day 8 and the proportion of patients with a reduction in concomitant ITP medications from baseline.
The study population included 49 patients; 17 in the placebo arm and 32 in the AVA arm. In both arms, the majority of patients were white, female, aged <65 years, not splenectomized, and had a baseline platelet count of <15 × 109/L. The most common reason for study discontinuation in both arms was inadequate therapeutic effect (7 of 10 discontinued patients in the AVA treatment group vs 15 of 16 discontinued patients in the placebo group).
In terms of the primary efficacy end point, the mean cumulative number of weeks with a platelet count ≥50 × 109/L during the 6-month treatment period was significantly higher with AVA treatment versus placebo (12.0 weeks vs 0.1 weeks; P <.0001). A significantly higher proportion of AVA-treated patients showed platelet responses ≥50 × 109/L at day 8 (65.6% vs 0%; P <.05), and decreased concomitant ITP medication use from baseline (33.3% vs 0%; P = .1348). A significantly higher proportion of AVA-treated patients showed improved durability of platelet response, defined as the proportion of subjects who had at least 6 of 8 weekly platelet responses during the last 8 weeks of treatment in the absence of rescue therapy (34.4% vs 0%; P <.05).
Patients in the AVA-treated cohort experienced a higher rate of treatment-emergent adverse events (TEAEs; 96.9% vs 58.5%); however, when adjusted for treatment exposure, the incidence of TEAEs, grade 3/4 TEAEs, and serious adverse events were similar in the 2 treatment groups. The most commonly reported TEAEs in both cohorts were headache, contusion, upper respiratory tract infection, arthralgia, and epistaxis.
These study results showed that AVA was superior to placebo in terms of the cumulative number of weeks with a platelet response, platelet response at day 8, and durability of platelet response in patients with refractory chronic ITP.
Jurczak W, et al. ASH 2017. Abstract 17.