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Published on December 28, 2020
Is Ropeginterferon the Best New Treatment Approach for MPNs?
Ropeginterferon alfa-2b is a novel and long-acting interferon that offers patients a new approach to interferon treatment. Dr. Jeanne Palmer, MD, hematologist/oncologist at the Mayo Clinic, joins host and patient advocate Ruth Fein to discuss the three formulations of interferon: the original short-acting interferon, peginterferon alfa-2a (Pegasys) and ropeginterferon. Dr. Palmer explains the results of a pilot program that showed that ropeginterferon may offer an approach that is more easily tolerated and could be the best option for an early, proactive approach to treatment.
This program is sponsored by PharmaEssentia. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.
Transcript | Ropeginterferon Offers New Option for Treatment of MPNs
Ruth Fein: Hi, everyone, I'm Ruth Fein. I'm an advocate, patient advocate, for Patient Power and I'm here today with Dr. Jeanne Palmer who's a hematologist and an oncologist at the Mayo Clinic in Arizona. First, thank you so much, Dr. Palmer, for joining us today.
Dr. Palmer: Welcome, I'm very happy to be here. Thank you for inviting me.
Ruth Fein: Our pleasure, we're looking forward to your insight. We invited you because we're specifically interested in a pilot study that you presented at ASH, which of course is the American Society of Hematology at their recent annual meeting. You presented a study, a pilot study, on ropeginterferon and we're really interested to hear about that. I know it's a very small study, but it was certainly of interest. Before we get started with you telling me too much about it, tell me the difference between ropeginterferon and the interferon that some of the patients and family members who are watching this might be familiar with.
What is Ropeginterferon?
Dr. Palmer: There's three formulations of interferon and I kind of like to think of it as sort of the development of interferon over time. The first form of interferon that people use was the original form that was a short-acting interferon and it was given three times a week. One of the challenges with that type of interferon is there was a lot of side effects associated with it.
Part of the side effect was related to the fact that because it was short-acting, you'd have market increase in the dose and then it'd come down. You'd have this up and down and when it was up, people would feel very poorly, they feel very flu-like and overall, not very well. Initially, back before probably the 1990s, interferon was primarily used to treat chronic myelogenous leukemia and hepatitis C and they said, "well, this is such a difficult form to tolerate, let's try to change it a bit."
They changed it to Pegasys, or peginterferon and what that is is that they attached the molecule onto the interferon that keeps it in the bloodstream for a longer period of time. As such, the side effect profile was less because instead of having this market up and down, you had more of a steady-state, and that's an injection that's given once a week.
This form of interferon that we used in our study was ropeginterferon. Ropeginterferon is again, a type of interferon that has a molecule attached with it keeps it in the bloodstream. However, the interferon itself is a bit more pure. It's a somewhat different formulation and the molecule they attached to it actually keeps it in the bloodstream for longer so the injections are given every two weeks to even once a month in some settings.
We enrolled 10 patients on this study, and we have three of the patients who are actually very early in their disease course, so we consider them low risk. Then we have seven patients who are in a higher risk category. And the lower risk category, they were generally treatment-naive, meaning they had not had any therapy given to them before and in the higher risk category, the majority of them had actually had treatment before and had failed that treatment and this was another attempt at treating them. There were two patients who were actually in the higher risk category based on the DIPSS (Dynamic International Prognostic Scoring System) scoring, who were treatment-naive and have not had anything prior to the interferon. How this study was run was once we identified patients for this study, we wanted to make sure they had measurable disease, meaning they had either spleen enlargement, or symptom burden, or anemia.
They were started on a very, very low dose of ropeginterferon. We started at 50 micrograms every two weeks. Now, just to give a bit of contrast and the study that is currently being done with this medication for essential thrombocythemia, the starting dose, is 250. We chose a lower starting dose and myelofibrosis, due to the concerns of this, of the blood counts being more sensitive to the effects of the interferon. Patients were given this dose and it was increased as much as tolerated. Over every two weeks, a dose, it went up depending on how well the patient had tolerated it.
One patient had a partial response, meaning that they were able to achieve improvement in both the symptom burden, as well as the spleen size. Two of the patients had a clinical improvement based on reduction in their symptom burden, and four of the patients had a reduction in their spleen size that constituted a clinical improvement, which essentially means 35% reduction in spleen volume.
Ruth Fein: Who do you see ropeginterferon being best for? What type of patients do you see the most optimism for?
Which MPN Patients will Ropeginterferon Be Best For?
Dr. Palmer: Where I would anticipate this would be most useful would be in patients who had early disease, who are just diagnosed, maybe have a bit of a symptom burden, maybe a bit of splenomegaly. However, I think that this would be sort of a proactive approach to trying to lengthen the disease course. Again, this is some extrapolation. I think that what we've learned from our study, in particular, is that number one, we were able to achieve some responses, and number two, the drug was extremely well-tolerated.
When I talk to patients about interferons in general, I say, "number one, the short-acting interferon is so difficult to tolerate that nobody tolerates it." The Pegasys is kind of in-between and maybe half of the people tolerate it. With the ropeginterferon, I had nobody who went off the study because they didn't tolerate the drug.
Ruth Fein: That's exciting, what do you anticipate the approval timeline might be? How far off are we?
Dr. Palmer: In discussing with the company, the hope is, is that the approval for it will be obtained sometime next year, perhaps even as early as quarter one, but I don't know if it's going to be earlier or later in the year. I think with the way the world is right now, it's uncertain how anything is going to proceed, but I think the hope is they're hoping to gain approval for polycythemia vera. However, as we've learned from Pegasys or the peginterferon, the pegylated interferon, that patients often are able to get it for other indications other than polycythemia vera. The Pegasys actually is not specifically approved for any of these diseases right now, but we still use it based on the data and everything that we have.
Ruth Fein: Is there a potential for disease alteration, an improvement in the disease itself, or is this a palliative, meaning just taking care of symptoms and making us feel better, which is not to be minimized, but does it have an actual effect slowing down the disease?
Can Ropeginterferon Slow Disease Progression?
Dr. Palmer: From the best we can tell and again, there are some people who have been using interfering for a long amount of time and have published some of that data showing the interferon really can improve it. They published some of that data, retrospective data, looking at it that showing that interferon may actually increase survival.
We do know from, or at least I know from personal experience, that I've had patients who I've had on interferon and I first, for example, polycythemia vera or essential thrombocythemia and although I have to ramp up the dose initially to achieve control of the blood counts, obviously in the setting, more of essential thrombocythemia and polycythemia vera, after a year of that, then you can start to down titrate the dose, and sometimes you can get people on very minimal doses of the drug achieving the same deep degree of control in their counts.
Ruth Fein: Well, that's great. All of that is great insight and thank you so much for joining us today for your time and for your expertise and always for your encouragement. Dr. Jeanne Palmer from Mayo Clinic in Arizona, thanks for joining us today.
Dr. Palmer: Thank you.