Investigating Momelotinib for Treatment of Myelofibrosis With Srdan Verstovsek, MD, PhD

At the recent American Society of Hematology (ASH) Annual Meeting, Dr. Srdan Verstovsek, Chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at MD Anderson Cancer Center, sat down to discuss his presentation on the results of research regarding momelotinib in treatment of myelofibrosis.

This podcast episode was recorded live by Oncology Data Advisor and ConveyMED at the 2022 ASH Annual Meeting in New Orleans.

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we're here at the ASH Annual Meeting. I'm here with Dr. Srdan Verstovsek, and he is here to tell us about his posters on momelotinib. Thank you so much for joining today.

Srdan Verstovsek, MD, PhD: Thank you very much for having me on the program. It is a very exciting time here at ASH 2022 in New Orleans, particularly when it comes to new drug development for myelofibrosis, the deadliest of myeloproliferative neoplasms. As we know, this disease is driven by the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, or hyperactivity of the JAK/STAT pathway to be correct, driven by different mutations. We call them driver mutations: JAK2, calreticulin (CALR), and myeloproliferative leukemia gene (MPL). The target of therapies that we have so far are aiming to inhibit that hyperactivity—that's why we call them JAK inhibitors.

Ruxolitinib, fedratinib, and pacritinib are approved therapies in the United States for different situations in life of patients with myelofibrosis. By and large, they control the spleen and symptoms. But the third key parameter that we cannot cover very well at all, and that has no drug approved, is the anemia. And that's really a reality, when you ask the doctors who treat patients with myelofibrosis—to control the symptomatic splenomegaly, general systemic symptoms, and anemia. Standard practice drugs cover the first two, but not the anemia.

Momelotinib is different. It is a JAK1 and JAK2 inhibitor but also it inhibits activin A receptor type 1 (ACVR1). That's another target on the liver that is associated with the iron metabolism. It leads to a decrease in hepcidin, the master iron metabolism regulator, and that allows more iron to be available for blood making. So, the benefit of momelotinib is, number one, to me as a physician, improvement in the red blood cells—a resolution or improvement in the anemia. The best example is elimination of transfusion requirements, so-called transfusion independence. The phase 3 randomized study in the second-line setting after standard-practice ruxolitinib, where that is more critical, shows that about a third of the patients eliminate need for transfusions or do not become transfusion-requiring. In addition, it makes people feel better and it can control the spleen like other JAK inhibitors. So, in one pill a day, you have a drug that can control, to a good degree, the three cardinal problems with myelofibrosis: spleen, symptoms, and anemia.

It's easy to give it with no major side effects. That is a factor that allows the most simplicity. You don't need to think about the dose adjustments or dose intensity, meaning how many patients stay on it for a prescribed dose—97% of people will tell you there are no toxicities. It's simple, it's safe, and it's effective. We expect this drug to be approved next June in the United States and later next year in the European Union. This will make a major difference, particularly for second-line patients after frontline ruxolitinib, because anemia is the major reason why they stop ruxolitinib. It compromises the dosing of ruxolitinib and any signs of disease progression as well. In the second-line setting, we don't have agents that would be able to control it, and momelotinib will be really a useful drug for a great majority of our patients with myelofibrosis.

Oncology Data Advisor: That's great. It's very exciting.

Dr. Verstovsek: The last factor here is, one of the presentations that I also gave on momelotinib is that you can easily switch from the ruxolitinib standard first-line to the second-line momelotinib; there is no worry. They're a look-a-like, plus there's benefit on anemia with momelotinib. Therefore, there is no concern if you need to change from ruxolitinib to momelotinib; you can do it overnight.

Oncology Data Advisor: What were your two posters specifically focusing on?

Dr. Verstovsek: The lack of any concern on switching from one to the other, and then long-term safety; it's very safe.

Oncology Data Advisor: Great. Anything else you'd like to share about momelotinib or about any of the other research that you've seen here?

Dr. Verstovsek: On momelotinib—because we are making people transfusion-independent or preventing them from becoming transfusion-dependent—the question was, "Are there any other benefits?" Understanding that anemia is the bad prognostic factor for survival. And guess what? The longer follow-up of this phase 3 randomized study and the follow-up from the prior studies with momelotinib some years ago now strongly suggest that transfusion independence is a signal for longer survival. That's an extra benefit that we did not expect. But, you know, you discover things as you go. The longer the people are treated and benefit on the anemia, spleen, and symptoms relief, the longer they actually live. And the primary marker for that survival benefit is transfusion independence. It's quite revealing, and we should think about that when we treat our patients with different drugs. And for this one, we should tell the patients that there is a possibility of life extension.

Oncology Data Advisor: Great. Well, thanks much for explaining all of this.

Dr. Verstovsek: My pleasure. Thank you very much.

Thank you for listening to this podcast recorded live at the 2022 ASH Annual Meeting by Oncology Data Advisor and ConveyMED. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at ConveyMED.io and OncData.com. Don't forget to follow us on social media for news exclusive interviews and more.

About Dr. Verstovsek

Srdan Verstovsek is the Chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at the University of Texas MD Anderson Cancer Center. Dr. Verstovsek is a noted leader in the research for myeloproliferative neoplasms, having led the development of novel therapies including the JAK1/2 inhibitor, ruxolitinib. As well, he is the founder of the largest myeloproliferative neoplasms clinical research center worldwide. 

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Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.