MPN Treatments in Development: Antifibrotic Medications and New JAK Inhibitors

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Topics include: Treatment

From the first annual U.S. Focus on MDS/MPN Meeting in Dana Point, California, Dr. Srdan Verstovsek from MD Anderson Cancer Center and Dr. Ruben Mesa from Mayo Clinic Cancer Center discuss new medications in development, particularly antifibrotic medications and new JAK inhibitors, momelotinib and pacritinib.  The experts explain how antifibrotic medications work and how they will affect the future of MPN treatment.  These medications, along with new JAK inhibitors, are giving patients more options, resources and hope.

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Transcript

Now, in the last session, to wrap up the summary of the meeting, we had a number of talks on myelofibrosis.  We learned that the ruxolitinib may help patients to improve their signs and symptoms for quite a long time. 

We just learned through follow?up on those studies that led to its approval how patients fare over time.  We learned that the interruptions of the therapy are not good because the people relapse with signs of symptoms rather fast and that over time there are some changes in the bone marrow and perhaps even in the molecular findings, but we don't really know what it means clinically. 

Now, there are other medications apart from the JAK inhibitors that have been developed, and a lot of talk is on antifibrotic medications.  We don't have much news on the clinical utility or clinical study results, but it appears to me that there is an area here that we are tapping in that is potentially very useful in the future. 

Dr. Mesa:

I definitely think so.  I think as we look at the current era we have—JAK inhibition has made a very significant impact for patients.  We recognize that there is continued room to kind of extend that benefit further and the hope that by helping to decrease some of the issues that come with the myelofibrosis part of the disease, that might help to slow progression, that might help to improve low blood counts, it might help to deepen the response to other medications. 

So to some degree I view the antifibrotic drugs as most naturally drugs that will be used in combination with other drugs as opposed to standing on their own.  That may evolve over time, but it's an interesting group of drugs, which we've already seen.  Some of them have been presented at ASCO and EHA, a medicine that both you and I are involved with, PRM?151, but there have been—in this group there have been some antifibrotic drugs that have been tested in the past that have not been successful and others that are looking successful. 

So it's a complex process, and I think we'll be testing a whole variety of different approaches to rolling back that fibrosis phenotype and hopefully making incremental deepening of the benefits that we see with current therapies. 

Dr. Verstovsek:

Now, in meantime, while we are waiting for news on success, hopefully success of this antifibrotic medications in clinical development we are here witnessing testing in Phase III approval studies of some other JAK2 inhibitors.  It seems that one medication doesn't fit needs of all the patients, or not all the patients are benefitting completely from one medication. And we definitely need more of the JAK inhibitors, because their profile is different. 

It seems that the toxicity profile is the area where there is difference in medication, so I'm talking about lowering the blood cell or not lowering it or providing some other undesirable side effects, one or the other, whether it's a mild neuropathy or a mild diarrhea.  So patients are different, medications are different, and we're looking forward to hear about momelotinib and pacritinib to other JAK2 inhibitors that are in Phase III studies, and we hope to have those results perhaps next year. 

For now, Dr. Jamieson gave us a good perspective how a need there is for more than one, and maybe one can be tried and if that fails another can be successful, because we don't have yet any knowledge about any resistance in the true sense of the word to any of the JAK2 inhibitors. 

Dr. Mesa:

I agree with you that it's very exciting in that I think patients will benefit from having a range of options and that these medicines are subtly different. I think they're all beneficial, and I've have had experience as you have had in the clinic using all three of these medications in different clinical trials and things of that nature. 

And the different profiles with momelotinib and pacritinib might mean that there are other patients in MPNs who might benefit there as front line or second line.  They may be more amenable for certain combinations based on their toxicity profiles. And, of course, JAK inhibitors might benefit patients with other types of diseases outside of MPNs, and the differences between them might be more relevant in other diseases than they are in MPNs.  So I'd say the deeper the bench really the greater the resource for patients with MPNs. 

Dr. Verstovsek:

Thank you very much, Ruben.  This was a lovely discussion.  Thank you all for joining us here in California at the first United States Focus on Myeloproliferative Neoplasms and Myelodysplastic Syndrome.  Thank you. 

Dr. Mesa:

Thank 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.

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Page last updated on September 10, 2014