For patients with myelofibrosis, previously treated with Jakafi, momelotinib could be a major drug approval coming up, according to an expert.
The JAK inhibitor momelotinib provided a significant benefit in symptomatic patients with myelofibrosis and anemia, according to preliminary data from the phase 3 MOMENTUM study.
Of note, patients in this study were previously treated with a JAK inhibitor approved by the Food and Drug Administration (FDA). Preliminary results from this study demonstrate that momelotinib may be the first and only JAK inhibitor to demonstrate efficacy in improving symptoms, splenic size and anemia. Dr. Srdan Verstovsek, a researcher on the MOMENTUM study and professor of medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, explained that this development is important because these are the three issues patients with myelofibrosis often experience.
“I'm really happy that we are in a situation where we are talking about potential for a new drug approval which covers the problems that we have not covered so far,” he said in an interview with CURE®.
Improving the Past
For the past 10 years, standard therapy has been Jakafi (ruxolitinib), with the option of Inrebic (fedratinib) added to standard care in the last two years. Both drugs have been shown to improve symptoms but worsen anemia, so they are limited in what they can do for a long period of time.
“There are (several) different areas of interest; just looking at quality of life is No. 1,” Verstovsek explained. “What drives the therapy in myelofibrosis is improvement in quality of life. We want people to feel better, and we want them to feel better for a very long period of time. Along (with) that, we want them to improve the bone marrow function, lessen anemia, we want them to have a higher red blood cell count, eliminate the need for transfusions — (and) that has been achieved here as well (with momelotinib) — and then we want to decrease that spleen as well.”
Verstovsek added, “You have here a new medication that is able to tackle all three critical parameters that bother patients with myelofibrosis, the three parameters that we treat … in a great majority of the patients. (Momelotinib is) certainly unique in its ability. (Jakafi) and (Inrebic) can control the spleen and symptoms but worsen the blood cell count, (but) not with momelotinib. (We) can improve quality of life, improve the anemia and improve the spleen — all three at the same time.”
In the MOMENTUM study, researchers assessed data from 130 patients with myelofibrosis who were unsuccessful with Jakafi and were treated with momelotinib, along with 65 patients treated with danazol after standard of care.
‘Extremely Significant’ Results
Results demonstrated a total symptom score of at least 50% or greater (with higher scores indicating greater symptom severity) in 25% of patients in the momelotinib group and 9% in the danazol group. The splenic response rate, which is the percentage of patients who obtained a reduction in spleen volume of at least 35%, was 23% and 3%, respectively. Verstovsek said that these results are significant, especially for this patient population.
“The results are extremely significant, particularly, for example, in the setting where the study was done, the study was done after standard practice (Jakafi) failed, so resistant/refractory patients to (Jakafi), where patients are much more anemic than at the beginning of the therapy with (Jakafi),” he explained. “They may have lower platelets, they still have issues with the spleen, and they still certainly have a bad quality of life. What do you do? The life is bad, life is short also.”
Verstovsek added, “In that setting, you could use, for example, in some selected patients this other approved JAK inhibitor, (Inrebic), but it worsens the blood cell count, so it's not really applicable. And you say, what do I do? We can use prednisone, we can use danazol or an anabolic steroid to perhaps patch the problem a little bit, but … it does not work. And momelotinib, particularly in this setting, is a discovery medication that has a potential to revise the outlook for the patients that have failed (Jakafi) by tackling all the critical three problems.”
Additionally, momelotinib was able to control and improve anemia in patients, which Verstovsek highlighted as a differentiating factor from other drugs in the space.
“Momelotinib has no medications to compare to. Because there are no other medications that tackle all the three problems at the same time. Certainly, we can say how about comparing the spleen control or the quality of life control with (Jakafi) or (Inrebic). But to say there is also a possibility of controlling the anemia (with momelotinib), then that's the differentiating factor. That's something that no other drug does. And that's why we are so excited about the prospect of having medication for our patients that will tackle those. So comparisons might be partial, but when you look at the total quality of what momelotinib does, it certainly stands on its own,” he said.
Verstovsek added that because momelotinib improves anemia, it also makes some patients transfusion independent, leading to a longer life, “which is my, as an academic physician, ultimate goal,” he said.
Severe or worse side effects occurred in 54% of patients in the momelotinib group and 65% in the danazol group, which, Verstovsek explained, is a testament to the safety of momelotinib. Specific side effects are not known yet; however, in the past with momelotinib, there has been occasional dizziness, indigestion or a skin rash. Verstovsek noted that this was not a leading issue that his team was concerned about.
Overall, he said momelotinib is safe and simple, especially as patients only have to take one pill a day, which doesn’t require much adjustment.
“Nobody worries about too much side effects. And that can eventually, through control of these parameters, particularly anemia, then lead to durability and life extension at the end. We need to study that life extension much more in detail, but certainly I'm a believer in being able to make people live longer with good control of signs and symptoms,” he said.
There are plans to submit an application this year to the FDA for potential approval of momelotinib in this setting. Verstovsek said that this is exciting and that may change the outlook for patients in this setting.
“Certainly if the drug is approved, as I would expect it to be in the very near future, momelotinib will be, by far, the No. 1 choice for therapy in the setting where it was tested,” he said.
There is also potential for momelotinib to be combined with other drugs, similarly to Jakafi, in the future to enhance its effectiveness. Verstovsek explained that since both drugs don’t have any leading toxicities, they may be good combination partners.
“I think it would be embraced by the very large group of patients right away where there was no option after (Jakafi) and in patients in frontline setting where you haven't even given any therapy, and they're already requiring transfusions or are significantly anemic and suffer from the spleen symptoms,” Verstovsek concluded. “It is qualitatively (a) different medication than anything so far. I think it will be a major, major drug for our patients with myelofibrosis.”
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