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Navitoclax in Combination for Myelofibrosis Patients

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Published on December 15, 2020

Phase 2 Study Combining Navitoclax and Ruxolitinib Sees Promising Results

A phase 2 study combining navitoclax with ruxolitinib (Jakafi) was presented at this year's American Society of Hematology Annual Meeting & Exposition (ASH 2020). The results are encouraging for myelofibrosis patients who have either had suboptimal results or who have stopped taking ruxolitinib, as well as patients who had not previously been treated and started the combination of navitoclax and ruxolitinib together.

Dr. Srdan Verstovsek, MD, PhD, Director of the Clinical Research Center for MPNs at MD Anderson Cancer Center, joined Patient Power co-founder and myelofibrosis patient Andrew Schorr to discuss the promising results and new treatment option that this study offers to patients.



Transcript | Navitoclax in Combination for Myelofibrosis Patients

Andrew Schorr: Hello and welcome to Patient Power, I'm Andrew Schorr in Palm Springs, California. Joining me from Houston, Texas is a noted MPN specialist, Dr. Srdan Verstovsek from The University of Texas MD Anderson Cancer Center. Welcome back to Patient Power Dr. Verstovsek.

Dr. Verstovsek: Thank you Andrew for having me on the program again, my pleasure.

Andrew Schorr: So, Dr. Verstovsek at the American Society of Hematology meeting we have new data about, I believe, a phase two study of a drug known as navitoclax being used to help patients in combination with ruxolitinib (Jakafi). Tell us about this study, first of all what does it mean and who is it for?

What Can You Tell Us About the Combination of Navitoclax and Ruxolitinib (Jakafi)?

Dr. Verstovsek: So the title reveals what this attempt in this phase two study is, it is the addition of another new medication, navitoclax, that's a pill that you take daily that would be enhancing the death rate of the malignant cells or make the malignant cells die off faster. It may complement the JAK inhibitor ruxolitinib. So the title of the study is, The Addition of Navitoclax to Ruxolitinib, and it's a combination to enhance what ruxolitinib does. Possibly there is some synergism between the two drugs, perhaps one add another benefit to another. So, we are exploring a possibility of two drugs providing optimal benefits to our patients with myelofibrosis.

Andrew Schorr: Dr. Verstovsek this drug, navitoclax, how does it work?

Dr. Verstovsek: Navitoclax works differently than any other drug in a clinical arena so far in myelofibrosis. It inhibits the protein called BCL-XL, which is important because when it's expressed, as is myelofibrosis, it prevents malignant cells from dying. So, by inhibition of that protein, BCL-XL, we're allowing malignant cells to die off. So, it's completely different, it's compatible to be combined with other drugs, the JAK inhibitors work differently or any other combinations. So, we'll see how things roll out. For now, we are exploring combination with ruxolitinib.

Andrew Schorr: So, with ruxolitinib then working on the JAK and this working in a different way, it could be a one, two punch?

Dr. Verstovsek: Exactly, the possible synergism between the two mechanisms that will allow control and elimination of the malignant cells.

Andrew Schorr: Okay. Let's understand from the study data, from what we know now and what's presented at ASH, how much improvement has there been? 

Has the Study Seen Promising Results?

Dr. Verstovsek: In fact with this particular combination, I should say that in my experience and I have been doing this drug development in myelofibrosis for a long time now trying to find the medications and the combinations that work best. This particular result of adding navitoclax to ruxolitinib, remember patients are on ruxolitinib already, they have suboptimal response, they have some benefit, but not optimal, you have here 27% response rate in the spleen and about the same in the symptoms. That means adding to ruxolitinib and 27% is the best response I have seen so far. So that means about half of the spleen gone from the start of navitoclax adding to ruxolitinib. So it appears to be durable, it's very effective. We are exploring the way, how is this actually done? Is it easy to do? Is it safe? There are other parts of the equation. 

Andrew Schorr: So, for people who are interested in this study now, who would it be right for, for further research?

Which Myelofibrosis Patients Would this Phase 2 Study be Right For?

Dr. Verstovsek: So because of these really valuable results, and as I said, and I have to emphasize this, these are really good results. We are seeing that this particular study is branching out, it's adding other clinical scenarios. So navitoclax is being studied within the scope of the same study right now, they add another arm, where patients that have never, ever been treated with any JAK inhibitors can receive ruxolitinib and navitoclax together from the beginning, let's see what they do from the beginning. And also another arm of the study, let's see what navitoclax does alone after ruxolitinib, some patients don't do well on ruxolitinib anymore. So it's branching out to other clinical scenarios. So it's widely open to any types of patients in a need either from the beginning, in the middle of therapy or after ruxolitinib.

Andrew Schorr: All right. So, looking at it together then we have the promise of a new combination that could make more of a difference for quite frankly, patients like me who are living with myelofibrosis. And is the hope, doctor, that besides the symptom management it could actually act on the cancer itself and reduce that?

Dr. Verstovsek: So, we would like the disease to go away, that would be the complete response. That's a pretty high bar, we are aiming with these combinations to move to that direction and eventually to cure people. That's the really absolute goal for us all to strive to, but there are steps to that and we are moving to that direction.

Andrew Schorr: Dr. Verstovsek lastly, of course, when you add any powerful cancer medicine patients wonder, are there side effects? So, for the patients who've received this medicine along with ruxolitinib, did it add side effects?

Are There Any Additional Side Effects to this Combination Therapy?

Dr. Verstovsek: Not too much at all. Actually, I'm pretty happy about not only efficacy, but the safety as well. However, it does cause thrombocytopenia, what this means is lower the platelets. So one needs to cautiously apply navitoclax on top of ruxolitinib not to counteract what the ruxolitinib does because you remember the ruxolitinib has to be adjusted based on blood cell count as well. So that's the art of the combinations, right? One needs to know how to do it and it has to be done not to achieve only efficacy, but it has to be done in a safe way. That's the part that we're still exploring.

Andrew Schorr: Okay. So just to sum up Dr. Verstovsek and as you said, you've been doing this for years, navitoclax with ruxolitinib exploring it further, the promise of it now showing efficacy, and now you'll explore it further. Combination therapy may be the name of the game for those of us living with an MPN like myelofibrosis, right?

Dr. Verstovsek: I think so. I think so. We at the beginning, 15 years ago, were looking for one drug that does it all because the goal would be to eliminate disease, but we have to be a little bit more modest. That's the goal, but let's focus on immediate control of the signs and symptoms and no one drug does it all. So, combination of let's say ruxolitinib and navitoclax, you are probably aware I'm sure of combination of ruxolitinib and CPI-0610, that's a different drug, it's a so-called BET inhibitor, combination of the ruxolitinib and luspatercept (Reblozyl) that's the anemia drug. So these are the three leading combinations that are being explored and all of them will be actually along your train of thought that you said they're going to be studied in a phase three studies, randomized studies for possible approval. So hopefully we'll have some of those, if not all of these combinations for our patients in a few years.

Andrew Schorr: Okay. Very hopeful message and thank you for sharing the interim data about navitoclax with ruxolitinib. Dr. Srdan Verstovsek from MD Anderson, thank you so much for all you do for those of us living with an MPN.

Dr. Verstovsek: Always a pleasure. Thank you Andrew and thank you everybody.

Andrew Schorr: Okay. I'm Andrew Schorr. Remember knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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