Ruben Mesa, MD, Discusses Momelotinib in Patients With Myelofibrosis

Ruben Mesa, MD, Mays Cancer Center, UT Health San Antonio MD Anderson, discusses the randomized, double-blind, phase 3 MOMENTUM trial evaluating momelotinib in patients with myelofibrosis (MF) who are symptomatic and anemic.

Transcript:

Hello, I'm Ruben Mesa. I'm the executive director of the Mays Cancer Center at UT Health San Antonio MD Anderson.

Oncology Learning Network (OLN): What existing data led you and your co-investigators to conduct this research?

Dr Mesa: Patients with MF have a chronic leukemia that manifests as an increase in the spleen, symptoms, the risk of progression to acute leukemia as well as anemia. So they have a range of difficulties.

Our current standard of care includes JAK inhibitors, ruxolitinib and fedratinib, that have helped to improve splenomegaly symptoms, but have typically not been able to improve anemia or sometimes have even caused anemia.

Momelotinib is a JAK inhibitor that also inhibits ACVR1, and we had noted in earlier clinical trials the ability to improve splenomegaly symptoms, but also to improve anemia.

In part from this ACVR1 inhibition, we believe that that leads to the inhibition of hepcidin, a marker of inflammation that perhaps suppresses the creation of red cells in the marrow.

So we created the MOMENTUM study to specifically drill down on the impact of momelotinib for improving symptoms and anemia in individuals that had already failed ruxolitinib as frontline therapy for their MF.

OLN: Please briefly describe your study and its findings.

Dr Mesa: The MOMENTUM study was a study in the second-line setting for patients with MF.

Individuals that had symptoms. They had anemia and transfusion independence. They had failed ruxolitinib. Then they were randomized between momelotinib and the current standard of care for anemia, which is the agent danazol.

There's no approved therapy for anemia in MF, but by treatment guidelines and prior data, the androgens like danazol have been as active as anything.

Individuals were then randomized to momelotinib 200 mg a day plus placebo or danazol plus placebo. It was a placebo controlled study, although there was an active drug on each arm with primary endpoints in terms of symptom response, and then a range of secondary endpoints as it related to improvements in splenomegaly and symptoms.

We reported on our top-level data of which all the top-level endpoints were met.

Most importantly, first, a clear improvement in symptoms, which is a very significant negative for the quality of life of patients with MF. A clear superiority of momelotinib versus danazol for symptoms.

Second is we looked at a range of improvements in anemia, including transfusion-independent status and the rate of no transfusions. There was non-inferiority for transfusion-independent status, but clearly a superiority as a rate of no transfusions for the momelotinib arm versus danazol.

So danazol's active, just not clearly as active for anemia. But where momelotinib is vastly superior is both the symptoms, which is the primary endpoint, but also the spleen volume reduction, which was vastly superior for individuals with momelotinib.

Indeed, we view this not as an anemia drug, not as a splenomegaly drug, not as a symptom drug. It's a MF drug. It's helping with all of these difficulties that patients face, and certainly complements existing data we already have from the SIMPLIFY-1 and SIMPLIFY-2 prior randomized phase 3 studies that show the impact of momelotinib on all of those critical parameters for MF.

OLN: Were any of the outcomes particularly surprising?

Dr Mesa: We were excited to see them. We certainly had anticipated that we had known from the immature phase 3 data momelotinib was fully active against each of these parameters.

We were excited to see those results validated in the conduct of this blinded, placebo-controlled trial.

OLN: What are the possible real-world applications of these findings in clinical practice?

Dr Mesa: Currently in MF, our current treatment guidelines have two different pathways.

One specific pathway for patients with anemia, given that we've had relatively few options that have been able to improve anemia, agents such as erythropoietin-stimulating agents, androgens and others.

In parallel, there has been a pathway of frontline therapy with JAK inhibition, ruxolitinib or fedratinib, versus transplantation with anemia largely not being addressed whether you went down one pathway or the other.

I think these data, one, helped to validate that in the second-line setting, patients like those in the MOMENTUM study would clearly benefit from this consideration. Second-line therapy, they have anemia, I think that is very clean.

I think what we will see over time is clear consideration of momelotinib for patients with significant anemia in other settings. In the frontline setting and as well as when we're considering second-line therapy.

I think beyond that, there are many non-JAK inhibitor agents currently in development in combination trials with JAK inhibitors, BET inhibitors, PI3-kinase inhibitors, BCL-XL inhibitors, telomerase inhibitors, many different agents. There will be natural questions again, whether some of these might be in a better circumstance in combination with momelotinib versus other JAK inhibitors.

OLN: Do you and your co-investigators intend to expand upon this research? If so, what are/will be your next steps?

Dr Mesa: One, we will continue to analyze these data as well as look at correlates and other pieces as it relates to predictors of response and further flesh out this piece as well as if momelotinib then has an approval, how that looks clinically in terms of the treatment guidelines.

The next steps for momelotinib now that has been well studied in the front- and second-line setting will be its approaches in combinations to further deepen response against molecular features of the disease or others with some of those other non-JAK inhibitor mechanisms of actions we discussed.