Published on July 30, 2020
Current MPN Clinical Trial with JAK Inhibitor Momelotinib
What type of JAK inhibitor is momelotinib? What is the inclusion criteria for this MPN clinical trial?
In this segment from a recent MPN Answers Now program, host Andrew Schorr talks to Sierra Oncology's chief development officer, Dr. Barbara Klencke on how momelotinib works and what MPN patients it is best for. They are joined by expert Dr. Christopher Hillis from Juravinski Cancer Centre in Ontario, Canada, and they share how the trial can meet certain unmet needs of MPN patients.
This program is sponsored by Sierra Oncology. This organization has no editorial control. It is produced by Patient Power in partnership with the MPN Research Foundation and BagIt Cancer. Patient Power is solely responsible for the program content.
Transcript | MPN Clinical Trial With JAK Inhibitor Momelotinib
Well, let's go on to Dr. Barbara Klencke, who's up at Lake Tahoe in California. Now she's the medical director for Sierra Oncology. Sierra is one of the companies emerging and she's helping lead a trial with researchers like Dr. Hillis about a drug called momelotinib, which is one of these brothers and sisters, one of these JAK inhibitors. Dr. Klencke, first of all, thank you for trying to propel research forward with researchers like Dr. Hillis. He was describing the unmet need and that is, even though we have now two JAK inhibitors, that won't be necessarily right for all patients or for all time, right? Help us understand the unmet need.
Thank you. Absolutely. Momelotinib is a JAK inhibitor. It inhibits both JAK1 and JAK2, two of the drivers of the disease, but it also, very uniquely, inhibits ACVR1, and what ACVR1 does is it promotes this anemia of inflammation. There's a lot of causes of anemia that patients will have who have myelofibrosis. The bone marrow gets fibrotic and scarred and you lose bone marrow space. Your spleen can pick off extra blood cells, splenic sequestration. Some of the drugs, ruxolitinib (Jakafi), for example, and other JAK inhibitors, generally worsen anemia. This is a real unmet need. It's a powerful prognostic factor. It presumably causes some of the fatigue and tiredness that people suffer from. Transfusions are really problematic. There's medical complications, but there's a big-time commitment. They're very transient. People go in for transfusions over and over again and they take all day or a couple of days sometimes.
The unique thing about momelotinib is its inhibition of, not only JAK1 and JAK2, but also ACVR1, and so if you eliminate or suppress or interrupt this anemia of inflammation, you actually see patients whose hemoglobin goes up. Some patients actually come off blood transfusions, or at least reduce the frequency. That's the major distinction of JAK inhibitors.
Okay. One other question for you is, as I mentioned, this is during the time of the coronavirus pandemic, and trials, not just in MPNs, anything, people have said, "Oh, my god. Are there requirements of the trial that will be difficult for me?" Transportation, multiple visits, blood tests, different things like that, what about that? First of all, has your protocol changed at all or how have you made it easier for patients to be in your trial?
We activated this clinical trial in December of last year. It was unfortunately before the COVID situation was even upon us. We actually didn't realize that we would need to make adjustments. That said, I think there's a number of things about our trial, first of all, our trial is a Phase III trial. It's called MOMENTUM, MOMENTUM is just the brand name of the trial, but it is a trial that we're looking for 180 patients in total over the next year. We've been enrolling for half a year now and we've got maybe a year to go. We are open in multiple countries around the world and it's a comparison, directly head-to-head comparison, of momelotinib and a drug called danazol (Danocrine), which has been recommended by some of the cancer guidelines as a treatment for anemia associated with myelofibrosis. It's for patients who have already anemia symptoms and have already had a JAK inhibitor, so it's for a patient population that's pretty specific.
What we did though when we wrote the trial is, we really thought about the natural standard of care and we tried to pattern our trial off of what people would normally need to be seeking in terms of medical care. There is, obviously, some up-front, additional work to get into the trial, the screening process and enrollment, and you have to have your first dose of treatment in the clinic, but both of the two drugs that you could be randomized to are oral, they're taken at home, and so that's helpful. It's a lot less complicated than being in the clinic repeatedly for intravenous treatments. It's also true that the primary endpoint is a symptom score, which patients report daily on a handheld device like a smartphone. And the second most important endpoint is a recording of how many transfusions someone gets.
Those are naturally going to be patterning off of the standard of care. We just report what would already be required. The normal cadence of visits is approximately once a month, with a few exceptions. I think that the trial is probably one of the better ones to actually get restarted when clinics are trying to minimize how much research they're doing. We have seen that. We've seen clinical sites become so overloaded with COVID issues that they can't manage everything at once and, if they're going to restart clinical trials and to put effort behind that, which we recognize that clinical trial sites actually need to really have a commitment to clinical trials, these are complicated things for them to do.
The first thing that some of our sites have done is to prioritize vaccines or other COVID treatments, but when you have a cancer population that needs care anyway and you have a cancer trial that doesn't have a high burden of additional activities, we've actually seen sites be able to prioritize this one, and so we've been very pleased about that. We're actually really nicely on target, despite trying to enroll over the last six months, and part of that is, as some sites say, they're unable to do so, it's just not safe or they don't have the staff. We've seen other places around the world to be able to enroll in the study. That's the start. Of course, if we see patients develop trouble or clinical problems, the clinic has a problem, we will adapt and we have plans for that, but luckily, so far, we've been able to do very, very well.
Okay. I just want to make sure I've got it right, and maybe let me ask Dr. Hillis as an investigator. So what Dr. Klencke has been explaining for this, one of the brothers and sisters, a JAK inhibitor, this would be for people who particularly have an issue with anemia and maybe have needed transfusions. And you're muted, Dr. Hillis, so just unmute. Did I get it right, Dr. Hillis?
Yes. You did and, certainly, that's what makes it exciting because there's an unmet need for folks who require transfusions, as we know some of the brothers and sisters, they beat up the red cells a little bit and actually cause them to go down, where we're hopeful that momelotinib does the opposite, it will boost the red blood cells and allow for folks to need less transfusions. And so, as Dr. Klencke mentioned, it does mean that the what we would call inclusion criteria, which are what needs to be going on with somebody in order to be eligible for a trial, do require that your blood levels are lower and that you've seen ruxolitinib before, it's certainly an important question that we need to answer.