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New Drugs Advance MPN Treatment Options

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Published on June 18, 2020

Despite the coronavirus pandemic, are clinical trials still moving forward? What about research for new treatment options like ropeginterferon and JAK inhibitors?

In this segment from our recent Answers Now program, host Andrew Schorr talks to MPN experts Dr. Naveen Pemmaraju from the University of Texas MD Anderson Cancer Center and Dr. Jeanne Palmer from the Mayo Clinic Arizona, about the status of clinical trials and research. Tune in now to learn more.

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. Patient Power is solely responsible for the program content.

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Transcript | New Drugs Advance MPN Treatment Options

Andrew Schorr:
Greetings from southern California. I'm Andrew Schorr. Welcome to this Answers Now program for those of us living with an MPN, a myeloproliferative neoplasm. And I've been living with myelofibrosis for about nine years, so I'm vitally interested. Joining us we'll have a number of experts. There's one of them that just popped on, Naveen Pemmaraju from MD Anderson Cancer Center in Houston, Texas. Dr. Jeanne Palmer joins us from the Mayo Clinic in Scottsdale, Arizona. And also joining us is, way up from Canada, Ottawa Canada, Phil Arner, who like me, has been treated for myelofibrosis.

Okay. Our topic and we want to thank the MPN Research Foundation for partnering with us, and Sierra Oncology for being an educational supporter of this program. Our topic is the future of MPN research after COVID-19. But I want to talk about during COVID-19 because we don't have an end date on this right now, and so we're worried. So we're going to start with Phil. But first of all, Naveen, thank you for being with us once again.

Dr. Pemmaraju:
Thank you, Andrew and Patient Power, for having me.

Andrew Schorr:
Okay. As a physician-researcher and Jeanne Palmer thank you for being with us too.

Dr. Palmer:
Yes, thank you for having me.

Andrew Schorr:
One question that came in for you Dr. Palmer we heard Phil talk about momelotinib , which has helped him along the way and gave him years and gave him life, and strength. That drug is not yet approved. So are there still trials with momelotinib and are those still open?

Dr. Palmer:
The answer to that, absolutely yes. Right now the MOMENTUM trial is open. We're going to be opening it here in the next month or so. So that is a study that's open. I actually am very excited about it opening because I have quite a few patients for it. But yes, that study is open. I think another drug on that same line is pacritinib. Which was another second line JAK2 inhibitor targeted for people who have low platelets. And that also has a study that is open right now for people who present with very low platelet counts, below 50, who we know are incredibly difficult to treat. So I think between these two second line JAK inhibitors really had difficulty I think with the parameters that were set for them with the initial studies. And I think these parameters weren't really designed to appreciate how much the drug could benefit patients.

So the good thing is, is that the companies see this and are really being resilient and persisting through. So I'm really hopeful to see that momelotinib and pacritinib both will be able to. Both of these drugs which provide an enormous benefit for patients will be able to continue to move forward, and hopefully be able to get approved. Because I think they both provide these wonderful opportunities for people to get relief from their symptoms without being tough on their counts.

Andrew Schorr:
Okay. Dr. Pemmaraju let me ask you about another area. Some people are on interferons. So there's a drug that's been in trials for a while, ropeg. Where does that stand in the research for that?

Dr. Pemmaraju:
This is a great question. Ropegylated interferon, or ropeg, which has a trade name in Europe, Besremi, has been one of the most important developments for me and for our groups in MPN. Especially the chronic earlier phases such as polycythemia vera. Importantly and maybe new to some of our viewers, this drug is actually just recently approved in Europe in patients with polycythemia vera with a very specific indication. Importantly three facts I would give you. One, it's an improvement over Pegasys, or pegylated interferon formulations that we know here in the US because it's really once every two weeks injection, rather than once every one week. That's already huge.

Two, it has less side effects it appears than our traditional pegylated interferon. And three, Jean-Jacques [Inaudible] and our European colleagues have presented now four-year follow-up data. That's called the CONTINUATION-PV, out of the PROUD-PV studies. And the results really look very encouraging now at four years plus follow up that people can stay on this drug for a long period of time. Less side effects than we expected. And possibly a signal for less MPN events such as thrombosis, like blood clots. Of course, longer follow up needed.

The good news is that this drug is being actively pursued for approval and other indications here in the US Andrew, so that data, or that pathway I should say is becoming public now that hopefully, we'll have this drug in the US in the coming two to three years. So stay tuned for that as those announcements come out.

Andrew Schorr:
Okay. So Dr. Palmer, as we do this program, there's a big world hematology meeting happening this weekend; European Hematology Association. We have the ASH meeting, the meeting in the US in December. Now we have the virtual European meeting, but you all are plugged in all of this. So in MPNs you're discussing what's happening, and maybe what's next. So, the title of this program is The Future of MPN Research, hopefully after COVID-19. Do you see a direction for those of us living with these conditions, myelofibrosis, polycythemia vera, ET - essential thrombocythemia, where things will get better, we'll have more options?

Dr. Palmer:
Absolutely. It's never good to have an MPN, but if you're going to have one, you're in a good time to have it. Because we do, you already talked about the ropeginterferon, which I'm really hoping gets approval. Having had some personal experience with the clinical trial here, that it's tolerated so much better. But I think right now we're not only coming with ways to alleviate symptoms, which is what we see with the JAK inhibitors, but there's also a lot of studies looking at ways to try to modify the disease. To try to perhaps even benefit the biology of the disease, rather than just making people feel better.

And a lot of these we're adding drugs onto another thing. So there's a couple of major classes. I think the first exciting class of drugs is the anti-fibrotics. So basically trying to reverse some of that scar tissue that builds up with patients with myelofibrosis. And there's a couple of them. PRM-151 which had some studies, those have subsequently closed. But I think they're developing it now, it was bought out by another company. And so that will be moving forward. And then the second one is AVID200, which is an anti TGF-Beta, it's another drug that's supposed to reduce fibrosis.

A second class of drugs is drugs that we're adding to Jakafi or adding to a JAK inhibitor that actually impact the biology of the disease. And we're taking a lot from studies that have been done with AML and MDS. And a lot of these drugs have various mechanisms that impact different I guess growth pathways. So things that make the cells grow, we try to block them, so the cells don't grow as well. And so we have a lot of these different blocking agents that are really showing a benefit. So I think these JAK combination studies are really exciting because they number one, provide the symptomatic relief from the JAK inhibitor. But number two, start to look at the biology of the disease.

And I think the other thing that's come out of COVID, and I've been maintaining my list of good things that have come out of COVID to try to remind myself that the world is changing, and there's going to be good things that come out of that change. Even though right now it's scary, one of the really good things is telemedicine. I think this is going to change clinical trials enormously that we're going to be able to have patients be seen by clinical trials. I even had a study that's basically said to me, "We'll do labs elsewhere. We'll take video visits." And they're really trying to be engaged to allow for more people to go on. And I'm hoping that since COVID is not going away anytime soon, I'm hoping to see more of this, which will enable more people to be on clinical studies.

Andrew Schorr:
I have a telemedicine appointment with my primary care doctor today for a minor thing. I had to get a little help in doing all the software. But then they say I'm good to go. It's going to be... I can't wait, it should be good. Naveen, I want to ask you about… especially for people with ET. Recently we had on a program my new best friend Ruth Fein who for over 25 years went from ET to PV, to then MF. But anybody with ET doesn't want to progress, or PV doesn't want to progress. So what about arresting the progression. Is the research going on there?

Dr. Pemmaraju:
Thank you for this question. For essential thrombocytosis, or ET, this has been one of the tougher areas interestingly so. We think of myelofibrosis as the more advanced of the MPNs, which it is in every sense. Especially for our patients, as Phil and you, and others have nicely explained. Polycythemia vera perhaps somewhere in between. But ET has been a historically difficult area. One reason is because we expect that the majority of our patients will live a normal life expectancy, which is a great thing to have.

And two, the problems that come out of ET are cardiovascular primarily. Either hemorrhage bleeds, or clots. And so a lot of the focus in ET research has been on cardiovascular health prevention and all that. And all that is still cornerstone and important. Even the dose of aspirin and all of this. I think the two breakthroughs in ET will be what you said. Is there a way to actually modify the disease at the level of the molecule? At the level of the biology, as Dr. Palmer was mentioning. So that's where your interferon, and this ropegylated interferon I think will be one of the most interesting programs to study. 

The second area will be JAK inhibitors. So we know that they've already been studies and approved in myelofibrosis, and now advanced PV after hydroxyurea. Two studies have been conducted. Dr. Claire Harrison, Dr. Srdan Verstovsek the MAJIC studies, ETs with fairly mixed results Andrew. So the jury is still out on JAK inhibitor for patients with ET. Even though it seems like an obvious maneuver, there's still some studies that need to be done there. So I think by in large the cornerstone for ET is still cardiovascular prevention, watching out for bleeds and clots, yes monitoring for development of pre fibrotic MF or overt myelofibrosis. And as you pointed out, the phenotypic mimicry or the transformation back and forth of these MPNs.

I want patients to appreciate what you said. You can start out with ET, go to PV, or PV to ET, go to myelofibrosis. I even had one patient who we published his report in the literature who went from PV to AML myeloid leukemia, and then back to polycythemia vera in this amazing time that we live in. So it's a brilliant point that you bring up. And also one last point is that as we get more and more molecular understanding, yes, there is still the shared family of PV, ET, and MF. No doubt about that. But I appreciate what you're saying as we now understand more, we can separate out the differences with ET, polycythemia vera, and MF. Not just from a clinical standpoint, but from a molecular biology. And that will inform our research in the next five years.

Andrew Schorr:
One more clinical question and then we'll have some wrap up comments with Phil as well. Dr. Palmer, we've talked on previous programs about whether let's say the JAK inhibitors should we develop COVID, have some ameliorating effect on the cytokine storm and really bad stuff that can come that can kill people. Do we know anything about that now? Any of us who are on a JAK inhibitor, I'm on one, say, "Gee, does that give me some protection should things happen with me with the virus?" Where are we now?

Dr. Palmer:
Well, there are several clinical studies going on. I know there's one that's based out of Toronto. I know they have one for pacritinib. There's one for Jakafi, ruxolitinib. So multiple JAK inhibitors are really trying to look at this specific thing. The quandary is that up front, they suppress the immune system. So that they potentially increase the risk of acquiring COVID. But then the problem with COVID is not just the upfront infection. It's the immune cytokine storm that happens after somebody has been infected, and that's what causes the organ failure and everything else.

And that's where these JAK inhibitors might help. That being said, we don't know for sure. The studies are being done. The studies are out there. We've seen lots and lots of stuff out there about all these drugs that we've been hopeful for that haven't quite panned out. So I don't know if JAK inhibitors will fall into it. I wouldn't tell somebody to start a JAK inhibitor, because COVID is out there. But I also definitely wouldn't tell someone to stop it because COVID is out there. The use of it should be done on a clinical trial for treatment specifically for COVID.

Andrew Schorr:
And Naveen, what about interferon related to having a positive effect in this time of the virus?

Dr. Pemmaraju:
Yes, essentially the same answer as Dr. Palmer nicely said. Our MPN therapies are interesting. They both have this predisposition towards creating an immune deficiency, an immune syndrome set up, both interferon and JAK inhibitors. And yet, some of their principles appear to be able to quell the cytokine storm, this natural host response to the virus. Same answer. You would not start or stop these drugs based on COVID alone. But your point is a good one. When you look at the research trials, some of these really do include and incorporate MPN-based therapies that are co-opted for COVID. It'll be very exciting and important to see that.

And also extend that to CAR T-cell therapies that cause a cytokine storm. HLH, which is called hemophagocytic syndrome. So this version 2.0, Andrew, of JAK inhibitors and interferon that you bring up, very exciting developments. And COVID research may actually help accelerate that. So as Dr. Palmer nicely said, let's add that to the Palmer list of possible good things in this otherwise tragic time. I really appreciate that Dr. Palmer.

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