BESREMi 4th dose

[lynxfluff]

Hey, guys! I see other members are sharing their move to BESREMi, so I thought I'd add my experience.

As background, I was diagnosed with polycythemia vera 8/2017 (at age 31) but waited until my kiddo was born to start treatment beyond daily aspirin. I'm JAK2+, TET2+, ASXL1+, AB at 55% in 2018. Since my symptoms (awful itching, headaches, visual disturbance) wouldn't go away with aspirin and phlebotomy, we started me on Pegasys in 9/2018. We'd gotten to the point that my bloodwork was well within normal range and my symptoms were gone with 45 mcg Pegasys every other week. I experienced practically no side effects.

Unfortunately, the insurance my job moved to in 2021 refused to cover Pegasys because it's off-label. (Thanks, BCBS TX...) In the interim, I received free meds from Pegasys' manufacturer, Genentech. My doctor was amped to move me to BESREMi in my January appointment this year though, for several reasons. One, he thought it would be a good fit since my body reacted so quickly and so well to Pegasys. Two, insurance coverage. For some reason, BCBS TX was quick to approve this even though it's so much more expensive. (Listed as $20k/2 syringes as opposed to $4200/4 vials I could get at least 12 shots out of.) Three, while Genentech's patient help team is great, the free Pegasys program has a lifetime limit of three years.

I had my first dose of BESREMi at 100 mcg on 2/13, with plans to up it 50 mcg each dose, taken every other week. Because of how it's worked so far, we have left it at 100 mcg per dose for all doses. LOVE the pharmacy - Onco360 is amazing. Quick shipping, phone line open after I'm off work, and the best part? Without me having to ask, they found and signed me up for a copay card. It's free. $20k of meds monthly, for free.

After that point, it's a mixed bag. My bloodwork is amazing. From the appointment before BESREMi, 1/19/22:

HCT 35.4 / RBC 4.07 / WBC 5.4 / Platelets 222

After 1 dose BESREMi, right before 2nd dose, 2/25/22:

HCT 37.2 / RBC 4.22 / WBC 6 / Platelets 255

After 3 doses BESREMi, right before 4th dose, 3/24/22:

HCT 34.9 / RBC 3.92 / WBC 4.7 / Platelets 204

A far cry from the OB visit where I first learned about my PV:

HCT 51 / RBC 5.73 / WBC 15.8 / Platelets 408

I have to say, out of all my symptoms I dreaded returning, it's the itching. And it's the one that has actually not restarted, thankfully. I am experiencing a number of other side effects I never had on Pegasys. Most disruptive is the significant fatigue I experience daily for at least 2-3 hours sometime between 2 - 8 pm. No real warning, just suddenly feeling heavy-headed and extremely exhausted. The fatigue kicked in right before my second shot and hasn't lessened yet. As a full-time employee with an hour commute home to a toddler by myself because my spouse works second shift... this is definitely taking a very close second place to how much I hate the itching.

This is often coupled with headaches and... how to describe... I can *feel my eyes move. Like there's pressure built up above and behind them. I'm unsure if the headaches start because of the eyes or the other way around. This side effect started two weeks ago, right around my third shot.

For my ladies and gentlethems, BESREMi may cause "changes in one's menstrual period." I don't have those, thanks to the magic of IUDs; however, this apparently includes cramps by themselves. So those are back. I have also experienced some low-level bone pain in my forearms; it's fleeting, but it's new to me.

My doctor, who is an MPN specialist, is currently not concerned. He's empathetic that my side effects are disruptive, and he encourages me to bring any changes to his attention. He and his PA are really great at not just utilizing lab results to determine care, so I know he's taking it seriously. He believes that as my body adjusts to the different interferon product, I should see these issues decrease in the next few months. I agreed that it was best to continue; I realize I had an abnormally easy onboarding for Pegasys and am not ready to bail on the only FDA-approved PV therapy yet, even if this sucks right now.

My liver is happy with the change. So far, no increases in those metrics. I am, however, having some back-and-forth in thyroid land. My TSH is all over the map but mostly high, and my T4 has decreased to the point it flagged slightly low at my latest visit. My doctor has scheduled me to see the endocrinologist and advised that it's likely they will put me on Synthroid; he'll of course defer to their opinion, but wanted me to be prepared that it's a possibility. I see them on 4/19 and will update if y'all are interested. His PA also suggested that the endocrinologist have me checked via ultrasound for thyroid nodules; the last few people they'd seen with similar patterns had undiagnosed nodules.

Added a pic of the BESREMi contents for anyone who's curious. It comes with two of these pre-loaded syringes, each in their own box. For your first prescription delivery, they send it with a thick packet of welcome info from PharmaEssentia, which includes fantastic dosage and administration guides with easy-to-follow pictures for people new to subcutaneous injections at home, a timer so you don't let your medication sit out coming to room temp too long, and a handy booklet about the medication. It also came with a sharps container and, thanks to Onco360, a welcome packet with goodies inside. Some "how to contact us" info, a magnet so you have their number handy, and some self-care items like Working Hands lotion.

[EPguy]

Thanks for the details. You have some important non-drivers, so your good results on INF are very good news. But you are the 1st here so far to note an inferior experience on Bes. I'm sure the mfr will find this real result to be of interest.

Could it be that you need only 50mcg? Your blood counts (very limited data however) show a strong effect relative to the PEG you transitioned from, and maybe the smaller dose would more closely duplicate the PEG results.

But you and your Dr are the ones to decide, and giving it time could be best.

Did you get the soft socks in the box?

[lynxfluff in reply to EPguy]

Right?? We were super surprised I reacted so well to Pegasys because of my mutations, but no complaints here LOL.

It’s quite possible. That, or spacing it out to monthly earlier than a year in. He’s loathe to change anything too much yet, granted I don’t have any side effects that are too wild. We’re all new to this, so we’re trying to not deviate much at the beginning.

I did not! I would feel slighted, but I can buy many soft socks with the copay I’m saving. 🤣

[EPguy in reply to lynxfluff]

The clinical trials required fluffy sox, so sad they don't have in your Rx😀

You've likely seen the post Defining INF Effectiveness. The trials did for real use a dose of near 500, we're all trying to figure that out.

[lynxfluff in reply to EPguy]

D: Oh man, yes, I can't imagine being on 500 mcg if 100 is kicking my butt. Big thanks to everyone who was involved in the trial for the rest of us because ugh.

[hunter5582]

This sounds on the whole like relly good news. Thanks for posting.

It is truly strange that your new insurance would not pat for Pegasys off-label but would pay for the very similar but FDA med that costs three times as much. My experience was exactly the opposite. Approval for Pegasys went right though but I had to mount a high-level appeal to get Besremi approved. It goes to show how important it is to understand the plan rules that drive decisions made by your insurance provider.

It sounds like you have a very good working relationship with your MPN Specialist and care team. That is really terrific. Just as an FYI - Dr. Ruben Mesa has a conversion from Pegasys to Besremi formula he recommends. If you are stable at 45mg Pegasys, his recommendation is to start at 67mcg Besremi . This was not part of the research PharmaEssentia did as that was focused on switching from hydroxyurea. That recommendation is on this presentation at minute 8:56. youtube.com/watch?v=KhKwDj5...(Not working as expected?)

The bottom line is that all of us switching from Pegasys to Besremi are part of the trial for how this will work in actual clinical practice. Everyone is going to learn over time how this will really work out. I suspect that many us us will do better on the lower doses. Some simply do not need the higher dose to attain a complete hematologic response. In my view, the increased intrinsic risks of higher doses are not warranted if you are achieving hematologic targets for PV without needing venesections.

I am also on 100mcg of Besremi. While I am tolerating it OK, it is causing some rashes/itching and I am experiencing lymphopenia. Neutrophils re also hovering slightly above/below normal. My MPN Specialist does not want to up the dose from 100mcg as he believes it will further depress the leukocytes.

Thanks again for sharing what you are experiencing. We all benefit from shared knowledge We are truly stronger together,

[lynxfluff in reply to hunter5582]

Yeah, my doctor and the PA were surprised too. It's the opposite experience from what they've had with most other patients' insurance providers. When we appealed my Pegasys denial, BCBS TX immediately shut the PA down because I don't have hepatitis, and their appeal team refused to acknowledge the follow-up document submitted showing how it exceeded BCBS TX's own off-label use rules. I'm glad your appeal was successful! Insurance can be an absolute nightmare.

My provider is from MD Anderson, so I'm sure he's aware. That was a great video! Thank you for sharing. I hadn't seen that one yet. Think I'll share it with my mom; it was a very clear explanation.

This is such an informative, helpful community! Just wish I'd known about it when I was first diagnosed lol. Thank you also for sharing. I saw your posts, which inspired this one. Hope your side effects clear up soon, and glad that Benadryl works to help the itching.

Oh!! And I hope your move goes smoothly! Just realized I don't think I said that on your post. 🤔

[hunter5582 in reply to lynxfluff]

My appeal was successful because I did not take no for an answer. I researched the plan rules and kept pushing it up the chain for an appropriate answer. 14 hours worth f phone calls. I ended up filing a Medicare Grievance. I kept pushing for answers and it turned out that their appeals department had processed the appeal improperly. By the time I had my doc refile, the Cigna Medicare Part D plan had already approved the Besremi.

There is a type of plan rule i have encountered when it comes to approval of non-formulary meds. You either have to fail on two formulary medications or there has to be a medical contraindication to the formulary meds. I ran into this issue when I was getting another medication approved. I wrote my own appeal for this and got it approved.

Theoretically, Besremi should be easier to tolerate than Pegasys but no one really knows. I expect it will be like everything else MPN. We are all different in how we present. We are all different in how we react to medications. We will find out over the next couple of years what the comparison between Pegasys and Besremi really looks like.

Please do keep us informed how you are doing with the Besremi. We all benefit when we share our experiences.

[Orangeboykitty]

I'm on my 8th dose of Besremi, but only taking 50mcg every 2 weeks. At that level side effects are much less than they were on Peg. I experienced wooziness for a few weeks but that's mostly gone, and I'm seeing a marked decrease in PV symptoms. Since it's keeping my numbers in check at 50mcg, there's no need to increase the dose. Maybe you need a lower dose as well.

[lynxfluff in reply to Orangeboykitty]

That's awesome! So glad to hear that your side effects and symptoms have both abated. It's quite possible it will be decreased, but my doctor was hoping to stick it out for a while, especially if they're considering starting a new thyroid medication. Turns out, those numbers have been wonky since I started Pegasys, but he wasn't concerned because they weren't too off consistently/I didn't experience thyroid-related side effects.

Who knows. He might change his mind after that appointment anyway, lol. Not a fan of the fatigue, but the rest of it is live-with-able right now.

[Meatloaf9]

You seem to be tolerating the besremi pretty well. You blood counts look good to me, let your specialist determine that. Are you able to get more than one dose out of each syringe of the besremi, I have read on this forum that some hematologists are giving multiple needles so that patients can change the needle and use the syringe until the drug is gone. I know that the drug manufacturer would not recommend that but just wondering. Hopefully you will be able to keep your copay card indefinitely. Best to you always.

[EPguy in reply to Meatloaf9]

I am slowly using the whole syringe, my Dr near insists on it. He says use it till it's gone or expires. I've asked several times, and no worries about this as long as it's kept properly in the fridge. I've had to practice the bubble thing.

As in other posts, Euro instructions call for two doses per syringe, so some sort of multi use is known. My guess is FDA had issues with the Euro instructions and device (instructions were one reason for FDA rejection in March '21) so they simplified it to what we see now in the US. The Euro device is also different from the US device, being a "pen" rather than a syringe. It has a dial on it, see here:

medicines.org.uk/emc/files/...

Bes Pen

[lynxfluff in reply to EPguy]

What a handy design!

[Meatloaf9 in reply to EPguy]

What ever happened to a good ole multi use vial and a insulin syringe?

[lynxfluff in reply to Meatloaf9]

I'm sure I probably could; I certainly have a plethora of replacement syringe tips from the Pegasys fulfillment group I was with before the free Pegasys program... I wonder if they fit the end of this syringe. 🤔

I have in the past been advised that if my prescriptions aren't being filled, the insurance may argue I'm not using the drug as prescribed and revoke my approval. So I'm tiptoing the line for right now. Worst case scenario, I do have some Pegasys left in their vials from before the switch.

[Meatloaf9 in reply to lynxfluff]

Hi again, I was not recommending to multi use your syringe, please consult with your Doc about that. I have not tried besremi or pegasys yet so I don't know about doing that. Still on HU since last July. I have just read here and on the MPN Research Foundation forum that some patients do get multiple uses from a vial or pen.It is very interesting that you were advised that you prescription could be revoked for not filling it as many times as prescribed. I would think that the insurance co. would rather spend less if they could. Just like many things that don't make sense to me.

[Elizka]

Hi there. Thank you for sharing your experiences. You mentioned something that struck a cord with me. "This is often coupled with headaches and... how to describe... I can *feel my eyes move." I have had migraines since I was 13 or 14, but since starting Besremi I've seen a different pattern, frequency and type of migraine. Blurry eyes and sort of feeling my eyes move. Then, the wavy line, etc. I had to start Emgality and Nurtec due to the increased frequency of migraines.

I wasn't sure Besremi was the culprit of the increase, but reading your comment on how your eyes feel leads me to believe it is. The good news for me is the CGRP inhibitors are a game changer for stoping the migraines in 10 minutes or less or possibly preventing them.

[Solyesh]

Thank you for the detailed update! I am definitely interested in what you find out about your thyroid. Since starting Peg my TSH has been steadily climbing (form normal range prior to Peg to 5.1 - 6.1 - 7.94). My TF4 has remained steady and in normal range the entire time. My MPN specialist is not worried - he says if it hits >10 then we'll have to take action. My GP was less sanguine but deferred to my MPN specialist for now (also focusing on making sure liver stays stable at this point since those readings were alarming)...

[Ovidess]

January 2023 reply: Hi all. I just started my first dose of Besremi this last week, for what now looks very much like both ET and PV. I started at 100 as my platelets have climbed ever higher (over a million) since diagnosis last fall. I scarcely suffered in reaction to the shot, aside from a little cross eyed feeling now and then, and some tiredness in afternoons. The nurse gave me the first injection. I looked at 400 of 500 mcg going into the medical waste can and asked about saving the drug for the next injection. She raised her eyebrows and said she knows folks do that, but she can't support it. She says any staph from our skin not only goes outside the needle but inside where it can't be cleaned out.

This is a shocking waste. Isn't there any company that at least provides doses of 250 instead of 500? I'd like to write to the government about the waste, but I'm afraid they would take it off Medicare entirely.

[Lillysue19850705 in reply to Ovidess]

Hi Ovidess, totally agree with you that 250mcg form should also be available. Pharmaessentia also applied for approval both 250 mcg and 500 mcg syringes in Japan. I don't see why they cannot also make the same application to the FDA. Maybe it's a marketing strategy, I don't know.

[Ovidess]

I've written to my federal rep about Pharmaessentia's flawed approach to selling doses, resulting in waste of product and expense to Medicare, insurance and unlucky patients. Rep said she's sending my comment up the ladder.

To update from my initial post above, I had to pause Besremi after 6 very effective doses because my liver enzymes went too high. I don't know if I can continue because Medicare and the clinic are arguing about coverage--TBD. Will keep all posted on this. In the meantime, not having had an injection for 19 days feels pretty good. I don't have those afternoon and evening slumps and feel pretty clear headed. Contrary to other reactions, I've had no visual migraines since treatment kicked in and platelets/HCT fell. During treatment I've had plenty of headaches, intestinal issues, etc seemingly from the Besremi. I already had thyroid nodules prior to MPN discovery; I will re-ultrasound this summer to see if the size continues to grow. The endocrinologist said my lipid and thyroid panels looked good but PTH was high.