Emerging Agents Pacritinib and Momelotinib for MF

Transcript:Harry P. Erba, MD, PhD: How about pacritinib?

Jamile M. Shammo, MD, FASCP, FACP: Pacritinib is the JAK2, FLT3, and IRAK1 inhibitor that has been studied in various clinical trials. It’s been shown to have less of an effect on cytopenias. This was further explored in PERSIST-1, when patients were randomized 2-to-1 to either pacritinib, 400 mg daily, or best available therapy, but it excluded patients who were receiving ruxolitinib. The primary endpoint, and this was respective of their baseline cytopenias, was spleen volume reduction at 6 months.

PERSIST-2 went on, also in a randomized fashion, comparing pacritinib—and here they utilized various dosages, 400 mg or 200 mg twice a day—and best available therapy, which included ruxolitinib in this situation. Both trials were more or less the same.

You’re talking about some volume reduction in maybe 19% to 20% percent in the investigational study, versus 67% in the best available therapy. Because of concerns about bleeding events, the trials were put on hold, I believe, in 2016. Ultimately, the hold was lifted.

Then we just completed accrual to a dosage-finding study with pacritinib looking at 100 mg daily, 200 mg twice a day, and 100 mg twice a day. Those did not allow crossover between the 3 arms. Again, spleen volume reduction by 3 months and those who responded could continue until about 2½ years. All those people enrolled had platelet counts below 100,000 mm³.

I do think that that perhaps there may be a role for this agent for patients who have platelet counts below 50,000 mm³. There’s a huge area of need, but more data are to come from this dosage-finding study.

Harry P. Erba, MD, PhD: OK. Finally, momelotinib.

Mary Frances McMullin, MD, FRCP, FRCPath: Momelotinib is also a JAK inhibitor.

Harry P. Erba, MD, PhD: Thank you.

Mary Frances McMullin, MD, FRCP, FRCPath: At least that’s how I think it’s pronounced. On the SIMPLIFY trials were phase III, newly diagnosed patients coming to treatment double-blind between ruxolitinib and momelotinib. The difference with momelotinib is that it was supposed to help the hemoglobin improve the anemia, and that obviously would be a major advantage.

The trial failed on the primary endpoint, which was a combined endpoint on the spleen size and symptoms, and therefore it was stopped at that point. Actually, there was very clear evidence on the secondary endpoint that many patients got improvements in their hemoglobin. I think it’s a very interesting agent, from that point of view. I was way down the line but had patients in that trial, and it certainly seemed to be effective in that patients who were needing transfusion were no longer requiring transfusion. As I understand, the drug has been bought by a different company, and there’s now a further trial planned where, hopefully, they can look at the specific issues.

Transcript Edited for Clarity