FDA grants accelerated approval to pacritinib for treating cytopenic MF

The U.S. Food and Drug Administration (FDA) has granted accelerated approval for pacritinib, a Janus kinase (JAK) and IRAK1 inhibitor, at a dose of 200 mg twice daily for the treatment of adult patients with intermediate- or high-risk primary or secondary myelofibrosis (MF) and platelet count <50 × 10⁹/L based on results of the phase III PERSIST-2 trial (NCT02055781).¹

Severe thrombocytopenia is associated with poor prognosis (i.e., greater risk of bleeding, symptom burden, leukemic transformation, and poor survival). The PERSIST-2 trial compared pacritinib (once daily or twice daily) and the best available therapy (ruxolitinib, 45%; hydroxyurea, 19%; prednisone and/or prednisolone, 13%; and watchful-waiting only, 19%) in 311 patients with MF and severe thrombocytopenia.

Efficacy analysis demonstrated that pacritinib arms (combined) were associated with:

• higher ≥35% spleen volume reduction (SVR) (18% vs 3% with best available therapy; p = 0.001)
• higher ≥50% reduction in total symptom score (TSS) (25% vs 14% with best available therapy; p = 0.08)

Pacritinib twice daily led to a significantly greater spleen and symptom response compared with the best available therapy. Red blood cell transfusion burden at 24 weeks was lower with pacritinib (Figure 1). In terms of safety, nonhematologic adverse events (AEs) were mild in severity; diarrhea was the most common AE observed with pacritinib (48% of patients on the 200 mg twice daily dose).²

Overall, pacritinib was found to be well tolerated with low-grade gastrointestinal AEs and rare treatment discontinuations, and more effective than the best available therapy in reducing symptom burden and spleen volume.² 

Figure 1. Summary of the PERSIST-2 trial*

AEs, adverse events; BAT, best available therapy; BID, twice daily; MF, myelofibrosis; OD, once daily, RBC, red blood cell; SVR, spleen volume reduction; TSS, total symptom score.
*Adapted from Mascarenhas et al.^2
†Allows ruxolitinib.
^‡versus BAT.

The MPN Hub Steering Committee member John Mascarenhas, recently gave an interview after his presentation on the PERSIST-2 trial results at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition.