Skip to Navigation Skip to Search Skip to Content
Search All Centers

Closing the MPN Treatment Gap: An Update on New JAK Inhibitor Trials

Read Transcript Download/Print Transcript

Published on June 27, 2017

Dr. John Mascarenhas, from Mount Sinai School of Medicine, joined Patient Power to discuss the status of JAK inhibitors in clinical trials, particularly pacritinib. Dr. Mascarenhas shares insight related to the current unmet needs in therapy for myelofibrosis, including thrombocytopenia.  He also provides information on the new PAC203 trial for pacritinib in 2017. 

 

Sponsorship of this program was provided by CTI BioPharma.

Featuring

You might also like

Transcript | Closing the MPN Treatment Gap: An Update on New JAK Inhibitor Trials

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.

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. 

Andrew Schorr:

Hello and welcome to Patient Power.  I'm Andrew Schorr.  Any of us with an MPN, we want to know where research is headed, and sometimes are there opportunities for us?  If we qualify, for example, for a clinical trial, could that give us an example of tomorrow's medicine today, fill a need for us in our personal medical situation?  So with us is a leading MPN expert, Dr. John Mascarenhas from Tisch Cancer Institute—did I get it right?  

Dr. Mascarenhas:

Correct. 

Andrew Schorr:

…from Mount Sinai in New York.  Thank you for being with us once again.  

Dr. Mascarenhas:

Yeah, thank you for inviting me. 

Andrew Schorr:

So let's talk about myelofibrosis.  What has been sort of an unmet need for people maybe where ruxolitinib (Jakafi)—which I've been taking for a long time, it's been working for me, how long will it work—or other people who for some reason it doesn't work or continue to work, is there an unmet need for another medicine, and where is research headed? 

Dr. Mascarenhas:

Yeah, I think there is definitely an unmet need for other therapies or additional therapies, so I can think of off the top of my head three unmet needs that I can identify initially.  One is patients with very low blood counts at onset of diagnosis or in their disease course that make it difficult to receive ruxolitinib because ruxolitinib, although a very powerful agent in reducing spleen and systemic symptoms, can also reduce blood counts.  So if you're already very anemic or thrombocytopenic, it may preclude you from benefitting from ruxolitinib. 

Other patients can be on ruxolitinib and then develop cytopenia, so develop transfusion-dependent anemia or limiting thrombocytopenia and limiting platelet count.  So there are needs for drugs either up-front or second-line to ruxolitinib that would fill unmet needs in niches of low platelets and transfusion-dependent anemia. 

Andrew Schorr:

Okay.  So where are you as a researcher in taking that in new trials that people could look into to see if they're in that category it might be something for them?  

Dr. Mascarenhas:

I think that the drug that is poised very well right now to explore that unmet need of thrombocytopenia in particular is pacritinib.  Pacritinib is a multityrosine kinase inhibitor.  It inhibits JAK2, FLT3 and other kinases and has been shown in two randomized Phase III studies to be an effective drug in reducing spleen size and improving symptoms and not inducing the same degree of thrombocytopenia and anemia as ruxolitinib has.  

So the PERSIST 2 study—PERSIST 1 is two studies really demonstrated a signal of activity and in my opinion demonstrated or clarified the toxicity profile associated with the drug which is predominantly gastrointestinal, which is a low-grade nausea, vomiting, diarrhea which usually is within the first month or two and is easy to control, and then patients can move on.  

There was a concern about excessive bleeding risk and potentially cardiovascular events that led the FDA to put a full clinical hold for a time period between March of 2016 and January of 2017.  After a review of the full data set, the FDA agreed that that was no longer necessary, and now the next step for the drug is a Phase II randomized study looking at different dose levels and the response and toxicity at those doses.  So we know from the PERSIST 2 study that 200 milligrams twice a day of pacritinib is an effective drug in meeting spleen and symptom end points and doesn't seem to lead to an excessive risk of death or bleeding outcomes. 

But to better tease that out a study will be conducted starting this year comparing 200 milligrams twice daily, 100 milligrams twice daily and 100 milligrams once daily.  So this is a study that's really targeting an unmet need, and that's patients who've been exposed to ruxolitinib and either have had unacceptable toxicity, progressive disease, transfusion dependence, low platelet count. And the investigator or the clinician that's taking care of the patient believes that they can benefit from an alternative therapy, and that's where the pacritinib Phase II study would really fit in for those kinds of patients. 

Andrew Schorr:

Okay.  So for someone in that category, then that's their situation and something they can look into, but taken for all of us in the myelofibrosis community, the MPN community, it's looking at expanding our options. 

Dr. Mascarenhas:

Correct.  I mean, ruxolitinib is a fantastic drug.  I do think anyone would deny that, but it's one drug in a space where there are a heterogeneity of patients and different needs. And we need an armamentarium of medications that will fit each niche and each need of individual patients, so you can personalize the approach better and so that you can have second-line therapies, third-line therapies, like most of oncology and hematology.  

Andrew Schorr:

Okay.  So for someone who is an MPN patient, a myelofibrosis patient, what dialogue would they have with their doctor to see would participation in a trial like this be worthwhile? 

Dr. Mascarenhas:

I think the first thing is bringing it up to that physician if the physician doesn't already bring it up.  So reviewing where are we today with the therapy I am on? Am I garnering all the benefit that I should get?  Are there signs of loss of response, for example, an initial improvement in splenomegaly and then perhaps expansion of the spleen, or initial improvement in symptomatology and then perhaps creeping back of some of the symptomology, or am I developing anemia that's requiring transfusional support and/or low platelets? And, you know, is an alternative therapy or an experimental therapy in line with trying to get me back on track? And I think that's really the discussion physicians and patients should have at every visit actually. 

Andrew Schorr:

Right.  Okay.  Well, Dr. John Mascarenhas, thank you for being with us on Patient Power once again, and we wish you well with all your research, and thank you for your dedication to those of us in the MPN community. 

Dr. Mascarenhas:

My pleasure. 

Andrew Schorr:

Okay.  Well, with Dr. John Mascarenhas from Mount Sinai and the Tisch Cancer Institute—I got it—in New York, it's great to be with a New Yorker again, I grew up there.  Anyway, thank you so much for being with us on Patient Power. 

And 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. 

You might also like