Compared with the best available therapy for myelofibrosis, pacritinib significantly reduces spleen volume and curbs symptoms, according to the PERSIST-1 trial.
Thus, Dr. Ruben A. Mesa told Reuters Health by email, the drug “remains an active agent with benefit for myelofibrosis patients, in particular for those with severe thrombocytopenia.”
In a May 20 online paper in The Lancet Haematology, Dr. Mesa of the Mayo Clinic Cancer Center in Scottsdale, Arizona, and colleagues note that available therapies can exacerbate cytopenias and are not indicated for patients with severe thrombocytopenia.
Pacritinib, a JAK2 and FIT3 inhibitor developed by CTI BioPharma, showed promise in earlier trials. In PERSIST-1, an international phase 3 trial, the researchers enrolled 327 patients with higher-risk myelofibrosis. There were no exclusions for baseline anemia or thrombocytopenia.
The patients were randomized 2:1 to receive oral pacritinib 400 mg once daily or best available therapy (BAT) excluding JAK2 inhibitors. Treatment continued until disease progression or unacceptable toxicity.
At week 24, 42 of the pacritinib patients (19%) had achieved the endpoint of an SVR of 35% or more compared to only 5 (5%) of those in the BAT group (p=0.0003).
A total of 90 patients randomly assigned to BAT (84%) crossed over to receive pacritinib at a median of 6.3 months and went on to get the agent for a median of 13.8 months.
The most common serious adverse events through week 24 in the pacritinib group were anemia (5%), cardiac failure (2%), pyrexia (2%) and pneumonia (2%). With BAT these were anemia (5%), sepsis (2%), and dyspnea (2%).
Over the course of the study, deaths due to adverse events were seen in 12% of patients in the pacritinib group and 13% of those in the BAT group.
These results, the researchers say, are echoed by those of the separate PERSIST-2 trial, which compared pacritinib (400 mg once daily or 200 mg twice daily) and BAT, including ruxolitinib, a selective JAK1 and JAK2 inhibitor.
Dr. Mesa said, "Additional studies confirming the minimally effective dose are forthcoming to build on the successful outcomes of PERSIST-2 where lower-dose BID dosing was safe and effective."
Earlier this year, the U.S. Food and Drug Administration lifted a clinical hold on pacritinib trials, which it had put in place following reports of patient deaths in the PERSIST-2 trial.
The PERSIST trials were funded by CTI BioPharma. Dr. Mesa reports support from the, which employed three of his co-authors and had financial relationships with several others.