Polycythemia Vera
Treatments to Watch Out For
Dr. Ruben Mesa
March 2022
In the second segment of our series with Dr. Ruben Mesa, the myeloproliferative neoplasms or MPNs specialist shares the latest on polycythemia vera or PV treatments to look to in 2022 and beyond.
This is the first drug approval in PV in almost a decade and the first that is broadly both in the frontline and second-line setting.
Dr. Ruben Mesa
Polycythemia Vera (PV) Treatments
The Patient Story: Dr. Mesa, PV, or polycythemia vera, there are some updates. There were a lot of different studies presented, as well. What were the big ones for you?
Ropegylated interferon alfa-2b
Dr. Ruben Mesa: Ropegylated interferon alfa-2b or BESREMi is the first drug approval in PV in almost a decade and the first that is broadly both in the frontline and second-line setting.
One, a series of information just further validating the drug that just became approved a couple of weeks ago. As I mentioned, the ET and PVera, we now have ropegylated interferon alfa-2b or BESREMi approved in PV.
This is the first drug approval in PV in almost a decade and the first that is broadly both in the frontline and second-line setting. We discussed it’s a small injection under the skin. It can help to control the blood counts.
Ropegylated interferon vs. hydoxyurea
In a randomized trial in Europe, a large study, it was found to be better than hydroxyurea for controlling the disease, both in the short term. But particularly in the long term, controlling the counts, maybe decreasing the molecular burden of the disease, the decreasing the amount of that JAK2 mutation may help to decrease the likelihood of the disease progressing. We’re excited that that’s approved. And there were a series of abstracts again just looking at longer-term follow-ups from those studies.
Hepcidin agonists
There is an addition, an interesting new approach to PV earlier in development, not yet approved, but of a class of drugs that are called hepcidin agonists.
Hepcidin is a molecule of inflammation. It is something that, when it is elevated in the body, stimulates the anemia of chronic disease. And the reason this was chosen to be tested in PVera is that it may help to decrease the red blood cell count, which is a goal in PV that we normally achieve through phlebotomy.
In phlebotomy, when we take blood away, has a negative impact that it makes individuals iron-deficient. And then iron deficiency may worsen the underlying symptoms of the disease.
PTG-300 (rusfertide)
So the first of these hepcidin agonists, of which we saw data at ASH, is one called PTG 300 or rusfertide. And with that medication, they saw that individuals were able to become phlebotomy independent. So I was able to control the hematocrit without the need for phlebotomy.
The goal of the iron levels in these individuals rising occurred, and most importantly, patients felt better. They were able to get off of phlebotomy. They were feeling better. They were less iron-deficient.
So that drug is going to go into a larger Phase 3 trial to again compare against a standard. And there are other drugs with a similar approach looking at trying to achieve it in different ways to see if one of these is better than the other. But there will be other drugs in this similar sort of class looking to control the need for phlebotomies, either in individuals who are not on other medicines or potentially in combination.
It’ll have an impact not quite ready for prime time, but it will have an impact in the near future, but available now for those that it’s appropriate for ropegylated interferon alfa-2b.
How was rusfertide impacting patients’ quality of life?
The Patient Story: Those are great updates. I was going to ask about this rusfertide just because I’m curious you talked about the iron deficiency. The phlebotomy and the bloodletting, it really helps avoid the blood clots. It’s a really big deal. And this rusfertide is hopefully going to help with the avoiding of the blood clots, but keeping the iron so you don’t have the iron deficiency.
How was that manifesting in patients, though? How was that impacting their quality of life when they were having to deal with? Oh my gosh, I don’t have the iron, and I still have to do this so that I don’t have these blood clots.
Dr. Ruben Mesa: So we know that the control of the hematocrit or the percent of blood by volume that are red blood cells is important to achieve to decrease the risk. And the negative with phlebotomies is, one, the hematocrit is always going up and down. It climbs up; you get a phlebotomy, it goes down.
When you go to get a phlebotomy, it takes time. It’s inconvenient. There may be a day afterward that you feel lightheaded because the blood has been taken off.
For the days that you need or phlebotomy but haven’t had one yet, you might have headaches. You already need a phlebotomy. You’re spending part of your time really above the target. So one, it’s a very uneven way of controlling the count.
And two, the iron deficiency really adds additional fatigue and other symptoms that are already present, so you put both together. It’s a tough combination.
I might envision that it could not only help people that currently are taking other medicines like hydroxyurea or things of that nature, but it might help people who just don’t feel well, who are getting phlebotomies alone. It might be a more even type of control, might be better quality of life.
Message to PV patients and caregivers
The Patient Story: Thank you for that. And is there any last sort of summarizing message you’d like to tell PV patients and caregivers?
Dr. Ruben Mesa: The approval of a new drug really is big news. It may not be for everyone, but it is something if you’re a PV patient, particularly if you’re on a medicine, to discuss with your health care provider to see whether it’s something that might be appropriate in your circumstance.