BREAKING NEWS - What Does the FDA Hold on the Pacritinib Trial Mean?

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Topics include: Treatment and Understanding

In February 2016, the FDA placed a full clinical hold on the trials for pacritinib.  To find out more, we reached out to one of the principal investigators for the trial, Dr. Ruben Mesa from the Mayo Clinic in Arizona. Watch as Dr. Mesa helps patients to understand why the FDA places holds on trials from time to time, particularly related to the pacritinib trial.  He also shares guidance specifically for patients that may have been on the trial and how they should move forward.

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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.  This program is produced with no outside sponsorship and as a service to the MPN community. 

Over the years, we've talked about drugs in clinical development for myelofibrosis.  One of them is pacritinib, but now the FDA has put a hold on the pacritinib clinical trials.  Joining us now is a leading expert in the field and a principal investigator for the pacritinib trials.  That's Dr. Ruben Mesa from the Mayo Clinic.  Dr. Mesa, why the change?  

Dr. Mesa:

As drugs are under development, the FDA certainly has a process for continuing to look at data as it's coming in on trials, and there can be periods of time where they, if they have a question, a concern, a need to take a deeper dive into the data, they can go on to either a partial or a full clinical hold. 

This has happened [in the past] even in the myeloproliferative neoplasm world, where we've seen holds which occurred with fedratinib, which did lead to the discontinuation of the testing of that agent, to holds that have been lifted, such as imetelstat, which is currently being tested in myelofibrosis.  So it's a mechanism that they have can have to put a pause so that data can be looked at in a much closer level. 

The information I can share regarding their concerns that they have posted publicly is they’re  [specifically looking] at the individuals who have passed away on the pacritinib trials.  There [are] two current clinical trials.  One, the PERSIST 1 trial, and second, the PERSIST 2 trial. 

The PERSIST 1 trial was pacritinib compared against the best alternative therapy so therapy chosen by an individual's physician.  It was a two-to-one randomization, so everyone—for every two patients on pacritinib there was one patient on best alternative therapy, and then patients could cross over after a certain amount of time or if they had progressed.  The trial was very broad in terms of the patients who were enrolled in the PERSIST 1 study, and that ends up being important in terms of the discussion. 

So since the PERSIST 1 trial allowed patients with platelet counts of particularly less than 50,000, there were many patients who were very ill who went on to that study.  The PERSIST 2 study [is] for individuals with a platelet count of less than 100,000, and again randomized between pacritinib and a therapy chosen by their physician, best alternative therapy.  PERSIST 2 would allow for patients who have previously been treated with other JAK inhibitors or multiple other therapies.  

So what this means is that the trials have included many patients who had very advanced disease, and there clearly are individuals who have passed away while on the study.  The FDA's pause in the hold is that they're looking at the individuals who passed away on the study and trying to determine whether the pacritinib had a hand in these individuals passing away or whether it is really just that they were very ill individuals, and it was unrelated to the pacritinib. 

So that really is the core issue which they are evaluating, and the investigators on the study, myself, Dr. Harrison, Dr. Verstovsek amongst many others, are working along with the trial sponsors of CTI and Baxalta to look at all of this information to provide to the FDA anything that they require so that they can make a determination regarding the trials, whether there's safety to move forward and their judgment in terms of the safety of the pacritinib.  

Andrew Schorr:

Dr. Mesa, of course, any patient who is in the pacritinib trial is wondering what should I do and what are the options for me?  What guidance do you have?  

Dr. Mesa:

So currently all patients who are on pacritinib—and in the United States is primarily individuals on the PERSIST 1 study, although there are individuals who are on compassionate use and a small number who remain on the PERSIST 1 study—they should be in contact with, if they've not already been contacted by the center that is prescribing them the pacritinib.  All the investigators have gotten guidance regarding the need to stop the pacritinib as well as options for those patients during this interval while they have come off the pacritinib. 

In terms of medical options, I certainly would encourage patients to really be discussing the options with their—with their physicians that have prescribed the pacritinib.  There are—every effort is being made to try to provide the information that's required in the hopes that the clinical hold will be able to be lifted.  A timeline truly for that is not known, although certainly everyone recognizes the urgency of the situation. 

For patients at the moment with their physicians their options, of course, would be to either, one, wait a period of time to see if the hold is lifted and they're able to resume on to the study; two, pursue whether there are commercially available therapies that are appropriate for them in discussions with their physicians, and that depends clearly on many things and is an individualized discussion between patients and their physicians.  Should they be considered for ruxolitinib?  Should they receive a different therapy?  Again, that's very much a discussion between patients and their physicians. 

Or thirdly, is there an alternative clinical trial that might be a reasonable option for them?  Those really are the three main options available to patients given we have no certainty as to when the clinical hold would potentially be lifted.  

Andrew Schorr:

Well, you've already provided a great deal of advice.  Do you have any further advice on this new development and what it means for patients? 

Dr. Mesa:

Sure.  So, one, this concern is a very global concern from the FDA regarding the patients on the study.  That being said, patients on the study, we have seen significant benefits that we have presented regarding splenomegaly symptoms and have not seen a particular side effect or toxicity that is of concern.  So one, for many patients this does not necessarily mean that they have been at any greater risk or would be at a greater risk moving forward, but it is clearly a fluid situation. And in terms of an individual's direct care needs, I certainly would urge them to really contact and be in contact with their physician who prescribed the pacritinib on the studies, both in terms of the options, as well as the FDA has asked for a status check of all the patients on the trial so that they have the most accurate sense of how well the medicine is working at the moment as well as any side effects patients are experiencing.  

Andrew Schorr:

Dr. Mesa, of course, thank you for being with us as there's breaking news in myeloproliferative conditions.  You're always there for us and so devoted, and we'll look forward to updates from you as more information is available.  

I'm Andrew Schorr.  You can count on Patient Power to keep you informed.  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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Page last updated on February 12, 2016