Andrew Schorr:
Hello, and welcome to Patient Power. I'm Andrew Schorr. We've assembled a great panel of MPN experts to discuss what's hot, if you will. What is significant for patients. Naveen, let me ask you this. We have some new drugs that are either approved or maybe coming. So, let's talk about that. So, for instance, many patients with PV have received interferon, kind of off label, Pegasys. Now, there's one that had been approved in Europe, that's approved in the U.S. Is that a big deal?
Can You List the Newly Approved Drugs for the Treatment of MPNs?
Dr. Pemmaraju:
Yeah. Thank you, Andrew. I think it will be. I'm personally very excited for our patients and I know many of my colleagues are. This is the Ropeginterferon that you mentioned, also known as Besremi, with a very nice, long-term follow up from our colleagues, Dr. Gisslinger and Dr. Jean Jacques Kiladjian. Andrew, this is exciting because of... I think really three reasons. One, as you mentioned, we have the historical data from Dr. Silver in New York and others over decades that there's a nice area for patients to have interferons in these earlier MPN. And so, the Ropeginterferon gives you an easier convenient schedule. So, it's less injectable dosing than the Pegasys, much less actually over time. Number two, you have the safety data over a long period of time. And then number three, you have the efficacy data over time as well. The approval is right now, just for P vera, as you mentioned.
And so, let's get that into the clinic, into America and other places. Let's see how that works for our patients. And then let's try to see if we can expand that indication. But I'm really glad you brought that up. And then Andrew, a second drug in P vera, specifically in P vera, is called PTG-300. It has a name now called Rusfertide. Also an injectable, also weekly. It's a hepcidin mimetic. And the goal there, Andrew, is, as we do phlebotomies in patients, can you give a drug that kind of as a sustained phlebotomy, if you will, or normalizes the blood iron levels. So, this has been a very nice promising phase two trial that we... We will review data here at ASEAN. So, you have two separate programs for patients with P vera. When really in the years past, we didn't have anything like this.
Andrew Schorr:
Okay. Aaron, I want to ask you about a drug that may be approved. It's delayed right now as we do this, but pacritinib... And this whole idea of whether people with myelofibrosis are not all the same, and whether there are different medicines for people with different blood counts, basically different properties. What about that pacritinib specifically?
Dr. Gerds:
Yeah, I think from just a super practical standpoint, I mean the more treatments we have for these diseases, the better. I mean, having two approved drugs in the United States here for myelofibrosis is kind of peanuts compared if you look at other diseases like multiple myeloma or breast cancer. So, definitely we're always excited to get more arrows in our quiver, specifically for pacritinib. The exciting part is we can deliver JAK inhibitor therapy to people with lower platelet counts. As we're learning more about the biology of progression, we're also learning more about the biology of different subtypes of patients with myelofibrosis and how different their disease may be from one person to the next. So, clearly, someone with a white count that's high, preserved hemoglobin, or normal red blood cells and not anemic or someone with preserved platelet counts. The biology of the disease is likely very different than someone who has very low counts across the board, particularly those with low platelet counts and anemia.
And so, using a different medication for those patients makes a lot of sense. And there's a lot of reasons why pacritinib might be better in that sense. Certainly, we don't see the suppression in the platelet counts, or we're at least able to deliver full dose JAK inhibitor therapy and get responses in terms of spleen and symptoms in those folks. And there's some presumed off-target effects on [inaudible 00:04:12] and other molecules that might prove beneficial in this certain subset of patients. So, I think, again, being super practical, more drugs and more arrows in our quiver to treat patients every day in clinic is always something that's incredibly welcomed. But, secondly, I think as we learn more about this disease and different populations within this disease, having treatments kind of for these subsets that would be applicable in these cases really is a welcome change too.
Andrew Schorr:
Well said. Aaron, I want to ask you about a new area of research. So, in so many of the cancers we cover, there's a lot of work going on about immunotherapy, and can we get the immune system to shut down the cancer replication of cells and things like that. And that's going on, big time, in hematology, right? We've been using transplant, which is in a sense in immunotherapy, right? It's somebody else's immune system. And that continues in for people who have advanced myelofibrosis. So, what about immunotherapy, whether transplant or other approaches for people as they progress with these MPNs?
What Are the Treatment Options at the Time of MPN Progression?
Dr. Gerds:
Absolutely. You know, I often say that transplant is the original immunotherapy. Well, at least more recent original immunotherapy where... Yeah, it works by someone else's immune system recognizing the cancer, whether we're talking an MPN or other diseases like leukemia as foreign and goes and kills it. I think the major challenge, of course, with transplant are the numbers of complications. Whether we're talking from low blood counts and bleeding, infection risk to this graft-versus-host disease, where, instead of just killing the disease, it kills other tissues that we don't want it to. And so, immunotherapy works, right? So, patients that you wouldn't expect to have long-term positive outcomes with disease, when they get transplant, they do. Certain population of patients do. And so, immunotherapy can work. And I think that's our first clue there. But we're kind of trying to catch a fly with a sledgehammer and it's very, very difficult.
So, I think really what the push really is now is to try to find other immunotherapies and other ways of harnessing the power of the immune system in a more precise way. And if we look at other diseases like ALL, there are ways to harness the immune system to kill the disease. For example, there are CAR T-cells where we engineer a T cell to go and attack the cancer cell and doesn't attack other tissues, ideally. And then bi-specific antibodies where one half of the antibody engages the immune system, the other half engages the cancer cell, brings them together and turns them on to go destroy the cancer cell. So, I think in MPNs the key will be identifying targets to go after because the technologies are there, but we just need the right targets to go after. The [inaudible 00:07:06] part is a lot of the targets on the, say myelofibrosis cell, are similar to the targets that are on normal bone marrow cells.
So, you would run the risk of wiping out the entire bone marrow with some of these aggressive immunotherapies. So, trying to find key pieces that we can go after... A lot of work is now going into vaccine therapies for these diseases. In particular, we talk about Calreticulin mutated disease because that one stands out. This Calreticulin protein kind of floats around outside the cancer cells and aren't in the cells and can be targeted in a much different way than we would target a disease that, say is JAK2 or MPL mutated. So, I think that is a certain area that is really exciting and holds a certain degree of promise right now for immunotherapies in the MPNs.
Andrew Schorr:
Wow. I've learned so much and I hope you'll stay with us on Patient Power as we keep you informed throughout the year. Thank you for joining us. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.
