Clinical Trial Exceed ET

[dogsandhorses]

I have approached applying to participate in this clinical Trial. It is to determine the efficacy of using Ropeginterferon alfa-2b-njft for the treatment of Essential Thrombocythemia. It has been approved for use in the treatment of PV, but not ET in the US, as I understand it.

When I read the study details it says that the injection will be every 2 weeks, and have a starting dose of 250 mcg, then 350 mcg week 2, working up to a dose of 500 mcg at week 4 for a 12 month treatment period. It goes on to say if you were on HU or anagrelide you will follow a pre-specified dose-tapering schedule. Not sure if that means your dose of HU, Anagrelide, or the Interferon.

My question is for people already taking this drug.

What is your dosage and frequency of use?

How has the amount taken affected you?

What are your side effects?

How long have you been on this drug?

Do you have PV, ET, or other?

What country do you live in?

I'm desperate to get off Hydroxyurea, but don't want to have worse side effects, or switch to another chemo drug.

[WRLM]

Hi dogsandhorses,

I just finished all the pre-testing for this same trial. I'm in BC, Canada and was diagnosed with Jak2+ ET in early 2023. So far I've only been on low-dose aspirin. They've scheduled me to start treatment January 11, but I'm still waiting for confirmation that I've been accepted into the trial.

There are quite a few people in here being treated with Besremi, and I'm sure some of them will chime in to answer your questions (you can also search for previous posts, which I found really helpful.)

If I am accepted I'll be slightly ahead of you in the process, should you decide to participate. I'd be happy to answer any questions along the way if you want to send me a private message. 😊

[dogsandhorses in reply to WRLM]

Thanks for the response, and offer of support. I'm sure I will take you up on it!

[hunter5582]

I have been taking Besremi for PV since Feb 2022. I started on Pegasys May 2021, then transitioned. I started on 100mcg then slowly transition in 25mcg increments to my current dose of 175mcg every other week. I was on 150mcg for much of this time but my HCT crept up and I upped the dose in November 2023. My MPN Specialist is based out of Johns Hopkins while my ongoing care is based in Virginia.

It appears that 175mcg will be the maximum tolerable dose for me due to the neutropenia. I am also experiencing lymphopenia. Other side effects include itching and occasional rashes. These issues are well controlled with Zyrtec (antihistamine). I also experience elevation in liver enzymes 3X Upper Limit of Normal. A daily dose of milk thistle extract returned the LFTs to normal limits.

Note that my PV includes thrombocytosis. The interferons have done an excellent job controlling platelet levels. I have also seen a decrease in JAK2 allele burden from 38% to 10%.

While I am generally a proponent of the low and slow approach to using Besremi, there is evidence in support of a more aggressive dosing pattern. The only way to determine the best approach is through clinical trial data. We are each different in how we respond to Besremi. The only way to find out how you will respond is to try. If it turns out you need a lower dosing strategy, the dosing can always be adjusted. How that would work in this clinical trial is something to discuss with the investigators.

I can certainly understand wanting to get off of hydroxyurea. I was refractory to and intolerant of HU. The interferons have been much more effective and far easier to tolerate for me. It is worth noting that Besremi is not a chemotherapy. It is an immune modulating drug. This is a significant difference.

The only was for MPN care to advance is through clinical trials. It is difficult to get the required number of participant in clinical trials for rare diseases. There are no guarantees about the outcome, but the potential for Besremi for treating ET is very promising. Your participation could help to avance care for ET as well as provide the opportunity to improve your own care.

Wishing you all the best.

[dogsandhorses in reply to hunter5582]

Thank you so much. I really appreciate your thoughts on this.

[hunter5582 in reply to dogsandhorses]

You want to consult with a MPN Specialist about your treatment options. Here are two lists.

mpnforum.com/list-hem./

pvreporter.com/mpn-speciali...

[dogsandhorses in reply to hunter5582]

I've seen this list, but none were close enough to me until now I've found one in Lawrence, Kansas. The clinical trial people in St. Louis told me about him. I wrote to him at 6:30 last night, and he answered me already!

[hunter5582 in reply to dogsandhorses]

Great news! If that doc pans out, please be sure to add to the list.

[monarch5000]

Pegasys interferon has been available for 18 years and works just as well as Besremi in all respects and often with less intense side effects. Pegasys is not FDA approved for ET but hydroxyurea isn't either - so that's not a legitimate excuse for your hematologist to refuse to prescribe it if you have trouble tolerating hydroxy. Here an MPN specialist in California talks about the minimal side effects of Pegasys: youtu.be/OsdoYoA1kLQ?si=QVQ...(Not working as expected?)

[monarch5000 in reply to monarch5000]

All this was known about Pegasy interferon and ET 13 years ago:

.

[dogsandhorses in reply to monarch5000]

Isn't it amazing that my hematologists here seem unfamiliar with the Interferon treatments, and only think of it as an "old drug" to "stay away from"?

[Island-Lady in reply to dogsandhorses]

my oncologist said the same thing as yours did, which is that Pegasys is an old drug. Luckily I read about it on this forum and was able to explain to him that the newer Pegasys is very effective. My oncologist is a wonderful man and is willing to let me drive my treatment. I do not have an MPN specialist as there are none here in Hawaii, and I have not found any that are willing to do video visits. I am hoping that I am able to work this out as I do know that a MPN specialist would be best.

as for Pegasys, I cannot say enough good things about it. I was on hydroxyurea for 2 1/2 years, which was one year too long. I was having horrible side effects, but wasn’t even aware that it was the hydroxy that was causing them. After reading posts about Pegasys on this forum I decided to switch medications, which was one of the best decisions I’ve ever made! on Pegasys I finally feel like myself again. I do not feel the least bit drugged and side effects are minimal if any.

I started on an extremely low-dose of 0.25 since I am sensitive to medication. I gradually increased to 0.50 every two weeks and I’m doing well on this. My platelets have been coming down extremely slowly, but since my symptoms are so few I am staying with this.

I am wishing you the very best and I’m glad that you are going to be able to see an MPN specialist.

[EPguy in reply to Island-Lady]

To Island-Lady:

Your Dr was helping make it confusing. It's actually the "PEG" part of Pegasys that made it modern. The old ones without it include "Intron A" which is likely what your Dr knew. Pegylation allows a slow release of the IFN, preventing the extreme hi-lo drug levels that Intron A caused. Peg also allows weekly or monthly dosing vs daily for the early IFNs.

Besremi is also pegylated in a "better" way claims the mfr. None of these are risk free as I painfully experienced, but they are generally safe.

[dogsandhorses in reply to EPguy]

Yes, I understand that the Pegylation is what makes it different than the historical drug. I wish my local doctors would look into it a little more on my behalf, but that hasn't happened.

[EPguy in reply to dogsandhorses]

Sorry for the confusion. I hope edited one makes sense.

[dogsandhorses in reply to Island-Lady]

You are lucky to have an oncologist that will listen to you. I haven't had that kind of experience. However, thanks to the St. Louis people in charge of one location for the clinical trials for Besremi, I have now found an MPN specialist in the Kansas City area, which is drivable for me. He has also emailed with me, which is something I have never experienced with a Dr. other than through a portal. I can hardly wait to see him. I am also scheduled for a consultation about cataracts, and from what I have read in this forum, I should get that done first. So, I will have to wait a little longer for the consultation.

I am very drug sensitive as well, so I appreciate what you have said about how you handled that.

Thanks for your response.

[EPguy in reply to dogsandhorses]

At the eye Dr it's also good to get a retina check. I got that before starting. This is one of the risks listed as "uncommon" to "rare" on the Euro label.

One strange eye effect I had on the 1st days was light seemed double bright, like daytime in the house. This was on 50mcg. That reverted to normal. Also unexpected, my vision focus improved to ~20/20 over the time on Bes. That is still mostly holding.

[dogsandhorses in reply to EPguy]

Ok, I will do that! Thanks so much.

[TimothyHLuff in reply to monarch5000]

One more good news for ET and PV patients is that Pharma& is now applying for approval of Pegasys' treatment in these indications in Europe. They could do the same for the US market. If it is approved, patients might have better access to the medicine and have more treatment options.

ema.europa.eu/en/documents/...

[gjh8733]

hi there

I was on HU and was switched to Besremi in Sept 2022. I started at 100ug/2weeks and slowly increased to 500 ug/2 weeks by January. Due to side effects I stopped treatment in Nov 2023. These were primarily drop in platelets to 86. I. Restarted at 100 ug/2weeks a free a month break. My hematocrit has increased to 49.2 so my dose is being increased to 150 ug/ 2 weeks and I will have a phlebotomy

I did share with the forum recently the additional side effects I feel associated with Besremi for me. These were increased irritability and anxiety during the periods when the dose was being changed, and at the 500 ug dose I would get uncomfortable facial flushing and mild headaches frequently. These could be treated successfully with NSAIDs and were not present at the 100 ug dose.

Best of luck!

[dogsandhorses in reply to gjh8733]

You must have PV if you are getting a phlebotomy. Phlebotomy doesn't really help with ET. I wonder if Besremi works as well for both PV and ET?

[gjh8733 in reply to dogsandhorses]

Apologies for not saying up from that I have PV

[KLCTJC]

I have PV and I have been on Besremi almost a year. We have done the low slow approach so last labs were the first in 100% normal range. Took about 9 mos. I am on 225mcg and feel really good. I now have hypothyroidism from it, but now have that controlled on medication. I have been pleased with the results and I have MS too which I found out right before I was to start Besremi. Saying a prayer that it helps that too as MS is also treated with interferon. I feel good, hoping that means something! Will find out in 2 weeks. I am in the US. And I hope at some point I will be able to reduce Besremi to once a month. Good luck! I came to this site before starting Besremi and all of these folks reassured me and I tried it. Very glad I did!

[dogsandhorses in reply to KLCTJC]

How did you get Besremi paid for, if you don't mind my asking?

[KLCTJC in reply to dogsandhorses]

I actually couldn’t believe it, but I was able to apply to the drug company and they approved it. I received it free from them. I added back my work insurance on top of my tricare that started now. Cingna should pay for it, but we will see.

[dogsandhorses in reply to KLCTJC]

Can you tell me which drug company that is? Was it Pegasys or Besremi? I want to know all I can before pursuing this like a dog chasing a rabbit!

[KLCTJC in reply to dogsandhorses]

Besremi. Pharmaessentia. You can get their info online and actually call them. They are great! I always get a live person too

[Joey1025 in reply to dogsandhorses]

Here you can find more information. I heard they are quite resourceful in helping patients.

pharmaessentiasource.com/fi...

[Solyesh]

As Monarch correctly states, HU is off-label for ET treatment in the US. While it is considered a "first-line" drug, it is not approved specifically for ET....Peg is similar in that it is off-label but has been used for ET for decades. As someone (ET Jak2+) who could not tolerate HU, I switched to Peg about 18 months ago. Few if any side effects and it has controlled all my bloods...I talked to my MPN specialist about switching to Besremi but as it is not approved (either) yet for ET only PV that would have been another uphill battle and the Peg is working great....

[dogsandhorses in reply to Solyesh]

I'm encouraged by your reply. I have worried a lot about the differences between Peg and Besremi, the cost of either of those, and finding an MPN specialist who actually uses those drugs. I think I have to do something because I think HU is literally killing me.

[monarch5000 in reply to dogsandhorses]

Where do you live? I suspect in a rural area since you said "the hematologists here seem unfamiliar with the Interferon treatments." We know where the interferon friendly specialists are and can direct you to the nearest one.

An alternative strategy is to continue to pursue the Clinical trial because that should automatically put you in touch with an interferon experienced hematologist. During the in person interview for the trial you could say something like: "I'm nervous about the high starting doses used for the Besremi trial and have read about Pegasys and wonder if you could prescribe that instead since I could start it at a much lower dose." This is the strategy I successfully used to get a prescription for Pegasys 7 years ago.

[dogsandhorses in reply to monarch5000]

Yes, I live outside of Oklahoma City. There are NO MPN specialists here, or in Dallas. Most other locations are not drivable to me, and flying could really add to the expense. The clinical trial people in St. Louis already gave me the name of a specialist in Lawrence, Kansas, which is drivable in 4.5 hrs. from me. I wrote to him last night, and he personally replied to me already. That's better than I could even imagine. I will be getting a consultation with him ASAP.

Thanks for your suggestions!

[Solyesh in reply to dogsandhorses]

Good luck! Many members here in the forum actually have a long-distance MPN specialist they see once in a while who works with their local hemo for on oging treatment - that might be an option.

[dogsandhorses in reply to Solyesh]

Yes, I believe that is the best option for me. I have just found one within realistic driving distance, and that's what I am going to do.

[monarch5000 in reply to dogsandhorses]

Here's an example of vital, life saving, information your local Oklahoma docs are not aware of. A group of specialists at the 2023 American Society of Hematology meeting in San Diego last month reported that about 25% of [348 patients total] ET patients who were diagnosed around the age of 20 ended up progressing to post ET-MF 3 - 20 years later except for one group that had been taking the drug interferon. The interferon group didn't progress.

.

[dogsandhorses in reply to monarch5000]

Thank you! I will share this with them.

[Ovidess in reply to dogsandhorses]

I actually had a few video appointments with an MPN specialist at the Mayo as I live in an area with no research hospitals, etc. It helped give me confidence to discuss options with my local onc/hematologist. I am now 66 and live in the US.

About my Besremi use, I started Besremi at the beginning of this year after being diagnosed with first ET then PV at the end of 2022. I did the traditional upping of dose from 100 mcg. Tiredness was main side effect, but the drug did bring down my extreme platelets and get HCT under control. By the time I got to 250 or 300 mcg, my liver was affected badly and my nervous first doctor took me off it. The clinic had also made a mistake and was injecting me instead of me self injecting. Medicare rejected it and a huge bill hung over my head until the clinic opted to take it off my record. I was off it all summer (and did not feel well in the heat) while I learned how to apply for the PharmaEssentia financial aid. I am retired and have not started any social security or tapped my puny retirement fund , so I got funded, at least for now. I think if I had regular money coming in I would not have gotten help. It took perseverance to work all this out. My Pharma Essentia representative was very understanding but it was a slow process.

Anyhow, now that I've been back on Besremi since last autumn, I have been very cautious--my new doctor and I are sticking with 100 mcg, no upping of dose. Lucky for me, this has brought down my platelets dramatically and promptly and my HCT is normally well within range. I no longer have migraines, yay, but tiredness and insomnia are with me a lot of the time. I do qigong and dog walks for exercise and have a vegan low inflammation diet for the most part. I am a bit paranoid about getting sick now, so I wear a mask in public and have evaded covid successfully. I hope to get down to one shot a month. That would be sweet. The black box warnings scare me thoroughly, and I did have one episode of a pounding heart in December. An EKG showed no problem, and all my blood work is ok in that regard, but I am scheduled for a stress test this winter, just to be cautious. I might add that I had other very worrying family issues during all this, so part of the insomnia, etc might be due to that. It sure is hard to place the blame for some health issues.

Best of luck to you all on your health journeys in 2024.

[dogsandhorses in reply to Ovidess]

Your story is very helpful to me. Thank you so much for sharing,

[Scottishterrier]

Hi I have always been on Hu for et jak2+ I was started on a high dose but now only take it on a Monday morning never had any problems just fatigue to be honest I wouldn't like to be on anything else better the devil you knowI stay in Scotland

Happy new year

Stay safe

Scottish terrier xxxx

[dogsandhorses in reply to Scottishterrier]

"Better the devil you know" is exactly what I had been thinking, but I really feel like HU is going to kill me with side effects. I'm taking HU for 5 years, and am down to 1 every 2 or 3 days, but the side effects continue. So I need to meet a new devil. I'll go a couple of rounds with him, and see how it goes.

[givingITMybest]

Greetings, I began taking Besremi last May, 250 mg every two weeks keeps my platelets in the zone. And actually, more of my bloodwork is in the normal range than it has been in years. I was diagnosed with E.T in September 2019. I'm 72 and had tried hydroxurea, then a trial of Bomdemstat and not the interferon. I live in the United Sates. Thus far I''m pleased with the Beremi. I did experience some depression and told my cancer doctor and I am not taking Sertraline which did the trick. That is the biggest side effect I get asked about frequently. If you look at side effects of any of these medications I'm not sure anyone would take anything! But overall I feel better on the Besremi. The injections are easy enough. The only drawback is traveling keeping the medication cool, but I was successful doing that as well. I hope my story is helpful. Good luck!

[dogsandhorses in reply to givingITMybest]

Thanks for your reply!

Were you able to get financial assistance with the cost of Besremi and if so, where?

[Ovidess in reply to dogsandhorses]

Have you or your doctor looked into Onco360 for financial assistance, at least in USA?

[givingITMybest in reply to dogsandhorses]

The PAN Fondation offers financial assistance. I pay $100/month and my insurance pays thousands more.

[sydunipete in reply to givingITMybest]

That’s good to hear. I’m currently on HU and am concerned about transitioning to Pegasys because I travel a lot. What methods do you use to keep everything cool and what experiences have you had at airport security.

I’m in Australia so my flights are long (24 hours with stopovers in tropical countries) and we don’t have Besremi. I have to travel with 6 months supply at a time.

Many thanks.

[EPguy]

The dose tapering refers to to reducing the HU as the Bes increases while watching blood counts. I went through that for PV in the US. But with the rapid increase in Bes in that trial, they should also be watching for counts going too low esp WBC. What is your current PLT level? What was it before you started any treatments?

On your question "How has the amount taken affected you?" my dose was too high and with a vaccine as a trigger I got one of the worst possible rare outcomes in the black box. You can see my posts.

But I would still recommend Bes if you are qualified for that trial. I assume they will be watching closely for autoimmune indications.

[dogsandhorses]

My platelets were in the 900's before I started the HU. They got down to the mid 400's taking 500 mg. daily, but the side effects were too much. I reduced dose to 500 mg. every other day, still side effects. I am now taking 500 mg. every 2 or 3 days, still have side effects, and my last bloods had my counts in the 600's. I go in 2 weeks for more blood work.

I'm so sorry you had such a bad reaction, and hope all is working better for you now.

[monarch5000 in reply to dogsandhorses]

You asked about how to afford interferon. Pegasys is around $4,200 a month and Obamacare (if under 65 years of age) and traditional Medicare insurance plans cover the vast majority of that. A PAN Foundation grant can cover monthly copayments. I've paid nothing for 7 years and counting. Because Pegasys is expensive and not FDA approved for ET, insurers often deny coverage at first, but a follow up letter from your hematologist explaining that their patient found hydroxyurea intolerable usually convinces them to cover it. Below is an example of a foundation grant approval letter.

For ET, there are important advantages of choosing Pegasys over Besremi. 1) It's 4 times less expensive (Besremi costs a stratospheric $16,000 a month). 2) A significant number of patients (but not all) report milder side effects. 3) It's available in 180 mcg vials and most patients need between 45-90 mcg per week. So this means that only 1/4 to 1/2 of the amount of Pegasys that is shipped to you each month (four 180 mcg vials) will actually be used and you can store the rest for up to 3 years. In other words, you can build up a spare supply over time in case of future supply disruptions or loss of insurance or foundation coverage.

.

[dogsandhorses in reply to monarch5000]

That is really helpful. Thank you for that information. It's really hard to figure all of this out by oneself.