New to MPN Voice

[Luthorville]

Hi,

I'm in my upper 40s, diagnoses with PV several years ago.

My platelets were just shy of 1.1M at the peak before starting Besremi in May 2023. At that time I was getting a phlebotomy about every 2.5 months to keep HCT below 45. Like others have said on this board, it seems the evidence is strong to keep HCT strictly below 45. My WBC had climbed to close to 12 as well at that time.

I started on Besremi with 50 mcg and it was gradually increased to 400. More recently my liver results (AST and ALT) had become elevated so my dose was reduced to 350 and my liver results over the past 4 weeks have returned back into the normal range.

Since being on Besremi my platelets are now stable in the 250k range (also normal). I am still getting phlebotomies every 2.5 months, but I'm only 9 or so months into Besremi and the ramp up was very gradual.

I'm shocked how few are on Besremi. My only side effects have been itchiness, especially not long after taking a shower. I find that Zyrtec or the generic version is easily 80% effective. I take it when I feel the itchiness coming on which happens every few days. As my dose has stabilized, the itchiness also seems less frequent and strong.

It has been hard to find good recent research and information spreads relatively slowly in the medical world. It appears that 12-18 months is when I would hope to have a reduction or elimination of the phlebotomies. Is that the experience of others?

Have others experienced improvement on Besremi on allele burden of the mutation?

My Besremi dose has remained on the higher side b/c my specialist said some more recent data suggested an improved chance at disease modification at higher doses. One of the obvious hopes of Besremi is that it will help with disease progression rather than simply treating some of the symptoms by just getting phlebotomies. Thoughts?

In terms of other drugs coming, I have been reviewing the results of Rusfertide and I'm not sure it has that much of an advantage. It had no impact on platelets in the study that I saw, but did control HCT much faster than Besremi. Still, with Besremi having the opportunity to modify disease progression, and being the only potential drug to do this, I don't understand why Besremi isn't far more widely prescribed.

This is my first day on this board, glad I found it. Sharing information for this condition is very helpful.

[hunter5582]

Hello and welcome to the forum. Glad you found your way here.

I have been taking Besremi since it was FDA approved. I started on legasys about 6 months prior then switched. In 2.5 years, I have seen a reduction in JAK2 VAF from 38% to 10%. I actually reduced to 9% in 18 months and have held stable for the last year. i am currently taking 175mcg, which seems to be my sweet spot. I only needed 1 venesection in the 2.5 years I have been on the IFNs.

I also experience itching and popup rashes due to the IFNs. I opt to take a daily Zyrtec to prevent this adverse effect. I tolerate the additional med well and would rather not be itchy. I also experience mild lymphopenia borderline neutropenia. This is a limiting factor in the dose I can tolerate. you can read more about my journey with Besremi in my "Updates" if you are interested in the whole story.

While I am a strong supporter of the use of Besremi, I do not favor the more aggressive dosing strategy. I do not believe the putative benefits outweigh the risks. While Besremi is beneficial for MPNs, it is not a benign substance. You will hear from may here on the forum that we prefer a Low & Slow approach. This is a common approach in clinical application by most MPN Specialists. Practical clinical application is not the same a clinical trials. Treatment with Besremi is best thought of as a marathon, not a sprint.

Wishing you all the best.

[EPguy]

On your question "Have others experienced improvement on Besremi on allele burden of the mutation?" this plot shows the trial results they got for Bes. The gray compares HU. In general members here do see results like this, of course with variations around these averages. Very few on this forum are at these later years so we don't have a lot of info on that here. The best responders in the studies do tend to get and stay near zero.

The extra red line shows approx a slight increase they saw at 6 years. This was also seen in older studies of Pegasys(PEG). I've posted on these.

My experience was VAF (allele burden) went from 14 to 8 in 11 months. It seemed to be heading to a best case reduction at 6%. But I was forced off (see below) and on Rux my latest VAF was 5%.

--

There are members who prefer the low and slow IFN way. I paid a tragic price for not doing that with a rare set of events, see my post "My Last Dose". Also in the Ropeg (Besremi) studies they did not find much correlation of dose to VAF. I read deep into the ropeg study and posted on this long ago. CHR (blood response) was more relevant. If so your CBC progress would be of interest.

If your Dr has new data showing dose/VAF connection it would be quite helpful to know more. My Dr went high for this reason but without any data I know of. (for me high was 140, it's esp variable with IFN)

--

On progression, in old posts we've discussed the reports with IFN being the best option (Rux had no PV data back then) while HU was also preferable to Phlbs. These are studies from the Dr. Silver MPN group.

Besremi 6 year

[Luthorville in reply to EPguy]

Great chart, I had saved that one previously. But the number of participants was quite small, so I was curious to see if that had also been the real world experience of others here. Good to hear that it is. I had had my allele burden done by both the blood test and bone marrow biopsy and had thought that the biopsy was more accurate. But according to this study both tests are very close to one another: ncbi.nlm.nih.gov/pmc/articl...

I've been on Besremi for about 9 months and my prior allele burden was 19. I need to get an updated number. It seems that based on the studies, that improving the allele burden is the best guess of whether the underlying condition is actually improving. Controlling HCT and platelets are indicative of an improvement, but the allele burden improvement is more important for disease modification.

I read your full post on your last dose. I'm so sorry to hear about it. What an awful experience. There seems to be such an incredibly wide level of responses to these drugs with some who do well and others who cannot tolerate it.

[EPguy in reply to Luthorville]

Most versions of that plot go to 5 years, they released the 6 year data recently, but never showed the plot. But I can't find the one I made so that 6 year line is my best recollection.

The roll over ContiPV study had 171 pts, not too tiny.

pubmed.ncbi.nlm.nih.gov/320...

There have been threads on blood vs marrow allele burden (VAF). While studies have showed them close mine was quite different on a % basis, BM=19, blood=14 at Dx. My Dr said, quite reasonably, that it most matters to compare the same type over time. Most pts naturally prefer using the blood.

VAF can be one underlying condition. But marrow histology can be at least as important. (cellularity, fibrosis). IFN can reduce both, but VAF reductions may not ensure marrow improvements. This was one concern in a paper from the Silver MPN group, that ceasing IFN at very low VAF could leave pathological marrow in place. (sorry I'm not well enough to find this, it's in my old posts) In prior posts I've noted that HU has shown potentially better effects on marrow than other therapies. Maybe a pinch of HU with the IFN would be good, this has not been trialed to my knowledge.

You're right that "controlling HCT and platelets are indicative of an improvement" and in fact this "CHR" is still the essential goal in ET and PV treatments. Notably CHR and VAF reductions are closely tied as discussed in old posts.

On the Last Dose, Hunter's description of "not a benign substance" is right on. Its more prone to the rare extremes than the other therapies hence its black box warning.

[KLCTJC]

I am about to be 42, in a little over a month. I have had PV for almost 4 years. I have been on Besremi a year and it has been working out well for me. I am on 225mcg and we went up super slow. That is what Dr. V from MD Anderson recommended. To go up slow and only increase once a month. So, that is what we did. I was like you, platelets were crazy, 1.7million, and then wbcs started climbing to 12-13, but then I found out I had MS so that put a wrench in things til I convinced everyone that it was going to help both conditions! So, I am an odd duck. But my last two sets of labs have been normal. Had labs last week and wbcs were a little low, 3.7, but platelets are like 300 and hct is holding at 44. No side effects on Besremi that I know of, other than dry eyes. The last time I went to MD Anderson I talked to my new doctor who took over after Dr V left to head up a new drug company, she said she felt most of her patients were controlled at 250-300mcg. I go see her in May and will see what she says. For me I am interested in the once a month dosing and knowing when that happens. But before I hardly ever had phlebotomy. A phlebotomy would last me 5 sometimes 6 months once things got controlled after my diagnosis. I was still interested in Besremi no matter what my number were as it has the chance to modify my disease. My local oncologist who I love, so sweet, he said he thought I was in remission. I take this with a happy grain of salt as we still have a ways to go, but was happy he said it! I think the reason you don’t see many people on it is cost. It took my local oncologist a year and half to get my insurance to cover it. And I literally just got the medication from my insurance this week and I saw on the ticket it cost $20,000 and peg is much cheaper. But I believe in Besremi for both my PV and MS, I think it is an amazing drug. I am so grateful that I was able to get it free for over a year and now insurance recognizes the importance of this drug. This site is the best! Everyone is so helpful and I refer to it all the time. And Hunter and EP guy are awesome, I feel like they also know me well by now! It is great to have a place where you can ask questions and sometimes just vent or keep us updated and feel supported. But I know how it feels, I was 38 when I found out with a 2 year old. These illnesses have really put my life in perspective. I tell everyone I love them more, I travel more, I try to always be present. And Besremi is going to make my life possible. I hope this has helped, if you ever have any questions I can answer let me know!

[Luthorville in reply to KLCTJC]

I think the average dose was a bit over 300 mcgs in the studies, but that may be wrong. I vaguely remember something like 328 or so as the average dose. I'm beginning to think that I might be too high still at 350 mcg. When I was increased, I basically went up by 50 each dose until my liver didn't like it and I backed off from 400 to 350 where I've stayed. But I am definitely going to ask about going lower. The idea of why take more of this potent drug than necessary does make sense to me.

[EPguy in reply to Luthorville]

This is a plot I made and posted in Sept 2022. It shows the range of doses used by members and in the two Ropeg studies. I also asked the specialty pharmacy for a guess of their knowledge. (this is more detailed than the plot I had been reposting) It seems the study got real later and used a wider dose range. The member data was as of that date. I tried redoing this survey but not enough replies.

BesDoseMembers

[Luthorville in reply to EPguy]

Interesting. How did you define CHR? No phlebotomy? Platelets in normal range? But what about allele levels?

The only issue I have on dosage is it can move around quite a bit.

Still the loose take away from the informal survey was that CHR was achieved with a lower than average dose if I’m understanding your data correctly.

[Luthorville in reply to Luthorville]

Also, it would be interesting to see the frequency of phlebotomy for those that received CHR. I am curious if the response is better for those that needed less of them, before starting the drug. I was about average.

[EPguy in reply to Luthorville]

I used the criteria from the trial. CHR meant less than 45 HCT without phleb, and under 450 PLT as I recall. They did not distinguish gender for the HCT, so all used 45.

There is no poll of members for allele, and for those on IFN and Rux we hope it is a moving target.

There wasn't an over all average dose, but the implication was CHR was possible for many using much less IFN than the trial used. This data is old, 2022, and with many more on Bes it likely looks different now. I'm no longer well enough to do this sort of work again, but maybe someone will give it a try.

[Luthorville in reply to EPguy]

I'd be happy to run point on it so that we can continue to track it and share it with everyone. It would have a real benefit since the results would be in real-time. The negative is that the data would be less reliable since we'd be relying on data provided by users.

In terms of a list of questions to ask specifically around the ongoing efficacy of Besremi, here's my crack at it below. I don't want to make it too long at the risk of deterring a response rate. We can always move the survey off of this website onto a more traditional survey website where the results can be shared in real time.

We are trying to consolidate ongoing data in real time to better understand the impact of Besremi on those of us that are using it. The objective here is to share data so that we can learn from the collective information. The data should be shared anonymously. I will provide graphs of the collected data.

When were you first diagnosed with PV? (date)

Do you have other conditions in addition to PV? (yes/no), If yes what are they?

When did you start Besremi?

Do you know your HCT, platelets, and allele levels at the time you started the medication?

Are you still on Besremi?

What is your dosing history (current dose and prior changes)

What are your current levels of HCT, platelets, and allele?

When was your last phlebotomy?

What was your phlebotomy frequency prior to starting any medication that targeted HCT?

What is your phlebotomy frequency now?

Thoughts?

[Dane12 in reply to Luthorville]

Hi,Maybe the following ?

- what is the driver mutation or triple negative?

- aware of any non-driver mutations (e.g. AXSL1, etc)

- MPN score at the beginning of the treatment and curent

- pruritus grade on a scale 1 to 10

- ferritin level

The last two is because the pruritus is one of the most common symptoms and it would be interesting to see the association with the ferritin level. In my case, in the beginning, even if I was CHR for many months on Besremi, still the pruritus grade was high. Only lately, it start decreasing and it is correlated with the ferritin increase.

[Luthorville in reply to Dane12]

The issue with the pruritis score is it is arbitrary for each person. There is no central scale to measure such as a formal test result. Also the Besremi side effects also cause itching and I think that stabilizes as the dose stabilizes. It would be hard to determine causality without isolating it. My pruritis started with the drug only. It was more severe initially but has dissipated some. But again, is that due to low iron or the drug?

[EPguy in reply to Luthorville]

As an inventor I've learned a key step is deciding what is the question, as you're doing here too.

--

My original focus was just the correlation of CHR to dose using the parameters from the trial. Seemed worth asking since the maker of Bes seems to be missing this message and it's central to the low and slow idea in this forum, as well as my tragedy.

I limited it to just 3 questions (and just two in the first round) for Bes with PV:

1- What is your current Besremi Dose? (If other than 2/month please note that)

2-Are you at CHR? (HCT at 45 for both male and female is ok here since the trial used this limit for all)

3- Is your dose stable?

--

It is nice to have more info, but as the info increases making use of it gets harder esp in a small sample size. In typical surveys fewer questions gets more responses, we all know that progress bar with online surveys. My 1st survey with two questions did better than the 2nd one with three. But there are a lot more pts here on Bes so pt patience for questions may be better now.

Further it may be good to include PEG now since it has entered wider use lately, but it requires a separate plot since dosing is different.

--

One challenge is tracking all the responses that dribble in mixed up in the thread, if you're a spread sheet type it should be easier, I'm not handy with Excel.

[Luthorville in reply to EPguy]

I live in excel so that won’t be an issue. Agreed on the number of questions. At the same time, I think people will see the benefit. Most people seem willing to post this information and many already do.

If the questions asked prove too many we can always reduce it.

[EPguy in reply to Luthorville]

You're set to do a much better job than I could. As you say there is a lot of info buried in the threads that require no member action. Look fwd to a fresh data set that I think even the experts should find illuminating.

One aspect worth seeking is the correlation of CHR to allele (VAF) reduction, this was found in the trial. Also found was a non-correlation of VAF reduction to dose. These should be worth a look here.

[hunter5582 in reply to Luthorville]

Sounds like a very interesting patient-lead analysis of data. Once you have the questions clear, I would certainly add whatever data I can. Thanks for giving this a try.

[Ovidess]

I don't know how my allelle burden has improved, but I recently wrote up a "bio" for this site and I'll copy it here:

For many many decades I had platelets between 500 and 750, but doctors told me that it seemed to be my "normaI" and that my visual migraines were not necessarily related to platelets. After some serious malaise in the summer of 2022, I learned my red blood cell count was off too. First I was diagnosed with ET, then quickly it was PV. I was on Besremi at the start of 2023, going up by 50 mcg every two weeks. I "had to" stop the drug in spring '23 because of a liver enzyme rise when I got to 250/300mcg. Although the drug was already doing its job, my doctor at that time was unhappy with all the risks of Besremi; he had wanted me to take HU. I did nothing all summer as I let my liver mend (no symptoms that I could recognize though I felt low) and worked out how to afford Besremi. I got "financial aid" from the PharmaEssentia company for the last months of the 2023, then got bumped off their list. In this new year I had to apply to the Pan Foundation for help in paying for the drug. (I'm on Medicare Traditional. )

I have been on a dose of 100 mcg from then until now. My body reacts quickly to the drug and recently (Feb 2024) my platelets went down into the high end of normal for the first time in thirty-some years! From over a million to 361,000 in 10 injections of 100 mcg, with the HCT totally in range. (In fact I question whether inadequate water intake was partly causing the HCT rise.) I do not want to take a higher Besremi dose. My energy level and erratic insomnia are quite enough for me to handle at this dose. I have different symptoms all the time, which makes me feel like a hypochondriac or whiner and makes it hard to keep track of what is caused by my PV and what by the treatment. I am ok for a few days after the injection, and then have little problems coming in waves-- for instance, an irritating burn/freeze sensation around my torso and arms or lethargy. Nothing I can't handle or really make more than a quick mention of at appointments, but yes, affecting my vigor more than I like. One recent problem is endless post nasal drip, which the oncologist says has nothing to do with PV or Besremi. Ah well, do they really know it all? Even specialists are "works in progress," I believe. Hence the function of this wonderful forum, to learn "on the streets" of the disease, from listening to other patients and their triumphs and pitfalls. May good health flow your family's way!

[Luthorville in reply to Ovidess]

Thanks for sharing. Whoa you got the visual migraines before too?? I have had only one small one since I started on the aspirin (and getting phlebotomies) and none since I started Besremi. I knew something was wrong before from the migraines.

Interesting that you've been on only 100 mcg and that has been enough to control your HCT. Any idea why you got bumped from PharmaEssentia? It is crazy to me that we litererally waste some of the medication by discarding it. I keep thinking that it's $10,000 I'm washing down the drain! When were you first diagnosed with ET and PV? It's worth asking about your allele burden too I think.

[Ovidess in reply to Luthorville]

Yes, the waste of medicine. I've written to my congressperson about the packaging of Besremi in very large doses that someone like me will never use more than a fifth of each injection. My rep passed on my citizen's complaint of wasted healthcare dollars (medicare and private insurance) to the Food and Drug administration and they sent me a foolish response saying, basically, as long as the rules for manufacturing,etc., are followed, we approve it. They washed their hands of my query. I would like Medicare to be concerned with the waste, considering the enormous expense to the public, but I don't seem to know which level of government will take on this problem. I also don't want them to cut us off from access to the drug. If you have any ideas, we should start a letter writing campaign!

I was diagnosed late '22, had a short course of Bes in early and late '23, and continue now with foundation funding in '24. I don't know why PharmaEssentia dropped their "sponsorship" of me. They'd implied I'd have to apply again in the new year, but they just cancelled and passed it over to my oncologist, who passed on my request for funding to a foundation. To their credit, I did not have any lapse in medication while this transfer happened. American healthcare is truly Byzantine. Other times it feels like a feudal system, or maybe a lottery. I've been lucky with it so far, but I can rankle at the inequity nonetheless.

[hunter5582 in reply to Ovidess]

Just saw your post. There are a few facts about medical economics and regulations that are in play. I would premise this with noting that I am taking 175mcg Besremi. It makes my skin crawl to waste 325mcg of a medication that costs over $7,5000/dose.

The cost of manufacturing a drug is only part of the cost the consumer is charged. The cost of developing a new drug averages at $1.3 Billion dollars. Additional expense is incurred in marketing, distribution, and post-marketing surveillance. The pharma companies must plan to recoup their investment in development while the drug is still under patent. With rare diseases, the cost of developing the medication is distributed across a smaller number of people.

In the EU, Besremi is offered in 250mcg and 500mcg prefilled syringes. This could be done in the USA, but PharmaEssentia would need to get FDA approval for making the alternate dosing available. There is little motivation to do this since the cost difference between the 250mcg and 500mcg doses would be miniscule if there was any at all. This can be seen with other drugs like Jakafi where 60 caps of 5-10-15-20-25mg cost = $14,308.00 regardless of the dose.

I have spoken to Medical Director and others at PharmaEssentia. They are aware of how patients feel about wasting so much expensive medication. Perhaps there will be alternative prefilled doses at some point in the future. Note that there would be no financial benefit to PharmaEssentia nor to the patients to provide the smaller doses. It would make us feel better about the wasting though.

I am not sure when you started on Medicare, but enrollment in Medicare makes one ineligible for patient financial assistance from pharma companies. This is a Federal regulation, not a pharma company policy. Under the Federal regulations, patient financial assistance from a pharma company is considered an "inducement", thus it is prohibited. While I believe this is a gross misinterpretation of what an inducement is, it is what the regulation requires.

The good news is that in 2025, there will be a cap on out-of-pocket medication expenses of $2,000/year for people on Medicare Part D. I believe the cap in 2024 is $3,250. While still a challenge for some, this is a significant improvement over the past.

Medical economics can be quite Byzantine in all healthcare systems, public and private. This is not unique to the USA. It is true everywhere. Medical economics are complex. The best thing any of us can do is to learn how the medical care system works then advocate for ourselves individually and collectively.

Wishing you all the best and success navigating systems of care.

[Luthorville in reply to Ovidess]

For other medications you can actually adjust the amount. You put on a new needle, and inject the desired amount. It's quite common. If we were able to adjust the amount so that we couldn't lose some portion of each 500 mcg vile, then they would probably just increase the price to reflect the lower sales of the underlying drug. I'm not sure that the cost would end up any lower, though perhaps it would be higher for some than others. Either way this is an awfully expensive drug.

[KyleeR]

would someone be able to tell me the difference in Besremi and Pegasus? Are they both interferons?

[Exeter21 in reply to KyleeR]

Yes Peg is used forbET a lot I am on that . Hunter on this site is on Besremi & will have all the knowledge to answer that too. I am sure he will explain when online 👌 Julia UK .

[EPguy in reply to KyleeR]

Here are two posts I discussed PEG vs Bes in detail, sorry if it's too much info. They are both pegylated interferon (IFN). The pegylation allows it to be taken only weekly or even monthly. The pegylation is very different between them, Bes naturally claims theirs works better. At least we know it's newer. The actual IFN part of the drug is also slightly different.

healthunlocked.com/mpnvoice...

healthunlocked.com/mpnvoice...

[hunter5582 in reply to KyleeR]

Pegasys and Besremi are both pegylated forms of interferon, but somewhat different formulations. Pegasys is peginterferon alpha-2a. Besremi is ropeginterferon alpha-2b. Besremi differs in using a mono-pegylated formulation. Besremi has a longer half-life than Pegasys, resulting in a biweekly rather than weekly dosing schedule. Besremi has an FDA label for PV. Besremi is in clinical trial for ET. Pegasys is in common use for ET and PV but its use is off-label. There is a theory that Besremi should be easier to tolerate than Pegasys due to its formulation. It will not be clear whether this is true without more clinical experience. It may be that the benefits will be the same but more data will be needed to know.

That is it in a nutshell.

[KyleeR in reply to hunter5582]

Thanks for the replies! I am based in NZ, and as far as I’m aware Pegasys is our main option but also after jumping thru quite a few hoops! Will ask about Besremi

[hunter5582 in reply to KyleeR]

It is certainly worth asking about Besremi, but I would not hesitate to seek Pegasys if that is your treatment of choice.

[Luthorville]

From my limited understanding they are similar. Peg was approved earlier and requires weekly injections. Besremi is 2 weeks potentially increasing to 4 after a year or so. Besremi, having been recently approved in the US in 2021 for PV is especially expensive if not covered by insurance at about $20k per dose.