Texas MPN Workshop 2021 | The latest data on momelotinib for MPNs

So, this agent has been in development for several years. It is most famous for the SIMPLIFY-1, SIMPLIFY-2 clinical trials, which showed activity in splenic volume reduction and activity in symptom improvement. However, they unfortunately did not meet the primary end points for those studies and did not result in approval for these agents for standard of care use.

We are fortunate to have excellent long-term follow-up data on this agent from the two studies, including patients who were treated with an intent to treat on the study, patient who were treated on an extended form of the study for extended access, as well as patients who are treated on the control arms, who were cross over to momelotinib. So, with the long-term follow-up maturing on all these patients and all these cohorts, we have plenty of additional data to go over.

So, a compelling evidence is that patients who have had a splenic volume reduction on therapy with momelotinib seem to have a long-term consistent and persistent response that was not lost in the majority of patients upon long-term follow-up, which is favorable and reassuring for two reasons. One is that the safety profile of momelotinib seems to be consistent with long-term use and the efficacy profile of momelotinib seems to be durable, which puts this candidate as a very favorable agent for future use for patients with myelofibrosis.

In addition, we’ve also had a [inaudible] and these also show favorable outcomes for patients with myelofibrosis treated on these arms with the particularly the patients who were treated on momelotinib, they have not yet reached their median overall survival on therapy. And this is after almost four and a half years of follow-up.

So, this also is encouraging, and it’s definitely exceeds the natural course of patients with myelofibrosis who are not receiving successful therapy. A more impressive results were for patients from the SIMPLIFY-2 study, in which their overall survival on therapy was over 30 months, which is an exceptionally long number for patients who have had a prior JAK2 therapy and are receiving the therapy in second line setting where the bar is usually 15 to 20 months for survival.

So, a 34 to 37 months survival as reported on the SIMPLIFY-2 study was exceedingly favorable. And to tease that even further, upon analysis of patients who have better responses for anemia, for patients who have actually achieved transfusion independence as described by the protocol, they had statistically significant improvement in overall survival compared to other patients on the study who have not achieved that secondary endpoint. So, we can actually predict which patients who would benefit mostly from the overall survival benefit from this therapy.

So, to summarize momelotinib, although did not achieve the prominent portion of the Phase III studies, long-term follow-up has shown favorable safety profile, durable responses, as well as an exceptional improvement in anemia where some patients have actually achieved transfusion independence. And this has resulted in improvement in their overall survival. This compelling data have led to a design of a specific Phase III study, the MOMENTUM study, in which patients received momelotinib versus best supportive care. And those patients, this study has completed accrual, and we look forward to hearing the outcomes of the study in terms of anemia responses and quality of life improvements.