Myelofibrosis Danazol vs Momelotinib a JAK inhibitor

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It’s my pleasure today to discuss with you the results of the MOMENTUM study as presented to at this year’s EHA. So, the MOMENTUM study is an incredibly important study in the development of a drug called Momelotinib is a JAK inhibitor that differentiates itself from other JAK inhibitors that are already approved for the treatment of myelofibrosis.

By a key off target effect on a molecule called a CVR one, also known as ALK2. It does have the kind of canonical JAK inhibition of JAK2 that we see with other JAK inhibitors. But again, the standout feature is this off target effect on ACVR1/ALK2 CVR. What that does is it’s a master regulator of iron trafficking in our body and actually affects hepcidin levels.

It can lower hepcidin levels, thus treating the inflammatory component of anemia. Anemia’s incredibly important problem in myelofibrosis. It is a diagnostic criteria as well as a prognostic criteria for patients with this disease. And there is some retrospective analysis suggesting that if we could impact anemia and improve it patients can have better survival in addition to better quality of life and potentially better resource utilization.

So, in this trial, this MOMENTUM study Momelotinib as the, as a JAK inhibitor slash ACVR1 inhibitor was pitted against Danazol in anemic patients with myelofibrosis who were previously treated with JAK inhibitors. These patients also had to be symptomatic and have enlarged spleens. The top line results were previously released in a press release from the company.

But in these abstracts, we have much more detail on the outcomes for the primary endpoint of this study. The primary endpoint study was improvement in symptom burden at week 24. Additional key endpoints included spleen vine responses at week 24, as well as transfusion independence at week 24. So, taking that last point is key because Danazol was selected as a comparator arm, because it is used to treat anemia patients with myelofibrosis as recommended by the NCCN and ESMO guidelines.

So, in those results, Momelotinib outperformed Danazol in terms of transfusion independence at week 24, moreover Momelotinib was able to shrink spleens as well as improve symptoms in patients to a much larger degree as compared to Danazol I think that is really the key take home point from this study. The top line total study results were presented by Dr.Versace’s check and the, special subset of patients with thrombocytopenia was presented by Dr. Venki at this year’s EHA meeting in two separate abstracts. And the reason that we focused on patients with lower platelet counts is that. Earlier trials of Momelotinib as well as this trial did include patients with thrombocytopenia.

In fact, we included patients with platelet counts as low as 25,000. So severe thrombocytopenia was included in this study and a fair number of patients did have severe thrombocytopenia. And I think that’s really important to note because. Currently available JAK inhibitors the ones Ruxolitinib and Fedratinib have limits on how much we can use them in clinic and what doses because of thrombocytopenia.

Of course, there’s a third JAK inhibitor that’s approved called Pacritinib that can be safely given to patients with platelet counts less than 50,000. So as more and more JAK inhibitors come into clinical use every day in the clinic, I think it’s gonna be really important how we try to separate these things out and which patient populations is their data for that supports the use of these drugs as well as.

Perhaps which patient populations, these drugs worked the best. And again, these were a lot of the top line results from this study, but the work going forward would really be in identifying the best populations for each of these JAK inhibitors. Now that we have almost an embarrassment of riches to the number of JAK inhibitors approved next steps for this particular drug Momelotinib is really regulatory approval.

This was a registration. And the data is being further cleaned up and correlated and is being put together for regulatory submission to the us FDA for hopefully regulatory approval in sometime in the year 2023 the quicker we can get this valuable medication to our patients, the better.