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The efficacy of pacritinib in the treatment of adult patients with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis was established in the PERSIST-2 trial.
PERSIST-2 enrolled patients with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis accompanied by splenomegaly and a platelet count ≤ 100 × 10⁹/L. The cohort included patients who were naïve to JAK2 inhibitor therapy and those with prior exposure to JAK2 inhibitors. Patients were randomized in a 1:1:1 ratio to receive pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or best available therapy (BAT). BAT agents could be administered alone, in combination, sequentially, or intermittently in accordance with standard of care. BAT encompassed any physician-selected myelofibrosis treatment, which might include ruxolitinib, hydroxyurea, glucocorticoids, erythropoietic agents, immunomodulators, mercaptopurine, danazol, interferons, cytarabine, and melphalan. BAT also included no treatment (“watchful waiting”) or symptomatic management without myelofibrosis-specific therapy.
In this trial, 311 patients were randomized to receive pacritinib 400 mg once daily (n=104), pacritinib 200 mg twice daily (n=107), or BAT (n=100). The pacritinib 400 mg once daily dose did not demonstrate an acceptable safety profile and is not an approved dosing regimen.
The demographic characteristics of the efficacy population were as follows: median age was 68 years (range: 32 to 91), 55% were male, 86% were White, and 14% were non-White. The pacritinib and BAT treatment groups were well-balanced in terms of age, sex, race, ethnicity, body mass index, and geographic region. Of the patients, 68% had primary myelofibrosis, 20% had post-polycythemia vera myelofibrosis, and 12% had post-essential thrombocythemia myelofibrosis. A total of 46% of patients in the pacritinib group and 51% in the BAT group had prior exposure to ruxolitinib. The median baseline hemoglobin level was 9.5 g/dL, and 23% of patients were red blood cell transfusion-dependent at study enrollment. The median baseline platelet count was 55 × 10⁹/L; 45% of patients had a platelet count < 50 × 10⁹/L. The median baseline spleen length, assessed by magnetic resonance imaging or computed tomography, was 14 cm.
Efficacy was established in the subset of patients who received pacritinib 200 mg twice daily and had a platelet count < 50 × 10⁹/L (N=31).
Among patients with a baseline platelet count < 50 × 10⁹/L (N=32), the most commonly used agents in the BAT group were ruxolitinib (39%), watchful waiting (32%), and hydroxyurea (26%).
The efficacy of pacritinib in treating patients with primary or secondary myelofibrosis was based on the proportion of patients in the efficacy population who achieved a ≥ 35% reduction in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging or computed tomography, in the pacritinib 200 mg twice daily and BAT treatment groups. The efficacy results for spleen volume reduction in patients with a platelet count < 50 × 10⁹/L are presented below:
In patients with a baseline platelet count < 50 × 10⁹/L, 9 patients (29.0%) in the pacritinib 200 mg twice daily group (N=31) achieved a ≥ 35% reduction in spleen volume, compared with only 1 patient (3.1%) in the BAT group (N=32). The between-group difference was 25.9% (95% CI: 4.3, 44.5).
The waterfall plot of the percentage change in spleen volume from baseline to Week 24 in patients with a baseline platelet count < 50 × 10⁹/L in the PERSIST-2 trial showed that the median percentage reduction in spleen volume was 27.3% in the pacritinib 200 mg twice daily group, versus 0.9% in the BAT group. The discontinuation rates were 26% in the pacritinib group and 44% in the BAT group, respectively.
FDA，2025.10
