New data about Besremi

[Wennn]

mops.twse.com.tw/nas/STR/64...

to someone still worry about Besremi

[Whitehair51]

This awesome! I just saw my hematologist who suggested that I try it once it has FDA approval for ET.

[Elizka]

The company has complied the latest research. Some marketing material but still a very visual overview of the success of Besremi. Thanks for posting.

[EPguy]

It is familiar to many of us. This one is mostly a sales presentation as implied by the web address that has "J.P. Morgan". One thing missing from their pipeline here (Page 24) is "Ropeg (P1101) Next Gen". It has been on their web site. If this has been dropped that would indicate an early failure of whatever Besremi's next act was to be. Maybe it was Beta? I'd like to see tests of Interferon Beta, vs the usual Alpha. I've posted on Beta which is less inflammatory.

I'm on Besremi since last Feb. I posted recently on a follow up to this plot. I used info they presented for a different purpose to create a year 6 result. I can't say it's the actual result but the data matched in two ways. It shows some loss of effect at year 6. There are some similar results with PEG. I asked my specialist about it and he said our body eventually gets accustomed to many treatments and reverts. It's a matter of how long for this to happen. Of course some Tx do cure some conditions, but so far not usually ours.

There was a large diff between "low risk" and "High risk" PV pts, low risks had allele avg of 5.6% year 6, (seen on page 16 of the paper) which is lower than shown here; the high risk pts brought it up a lot. These are defined:"low risk defined as age < 60 years without thrombosis history and high risk by either the presence of age ≥ 60 years or thrombosis history"

link.springer.com/article/1...

That said I'm happy to be on Bes even as I fit high risk by being age 62 at start of therapy.

They have this in future plans "Establish collaborations to pursue cell-based therapies (TCR-T)" These are the possibly curative immune therapies we all want that should put IFN out of business. But they don't say what they will add to the research others are doing here.

Ropeg Year 6

[monarch5000 in reply to EPguy]

No loss of molecular response with Pegasys after 6 years in the French PV1 study that involved middle aged PV patients who were offered the drug as a first line treatment:

graph

[Manouche in reply to monarch5000]

The results of this 6 years study make sense. There’s no evidence of a loss of effect after 72 months of interferon therapy.

[EPguy in reply to monarch5000]

That data looks nicer. As a Bes user I like it. Can you provide the report it's from?

It's actually consistent, this study was on middle aged patients. This is probably less than 60 years. Both this study and the Ropeg study show ~5% allele at 6 years for these low risk pts. (not accounting for the added risk factor of thrombosis which might partly be the extra 0.6% of the 5.6 in Ropeg).

The text and bar plots seem to have an inconsistency, the plot shows a rise at 6 years, matching some of the result I saw, but then a pleasant fall at 6+, the text goes only to 6 years and shows a fall. The ranges also don't match. Probably explained in the report.

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This is the reference I have been using. I've posted before. This and the Ropeg studies show loss of response at 6 years. In light of the age factor above, this study included pts up to and over 63 which likely explains its match to the Ropeg study.

ncbi.nlm.nih.gov/pmc/articl...

For PV, which is the data we're following, Pegasys in this plot had a low point at 5 years then up thru 7. This result is unhappily very similar to my plot from the ContiPV reported data. n is small in this PEG study, but larger in the Ropeg one.

The strongest indicator of this possible concern is that the Ropeg sponsors aren't publishing this data that they clearly have. They did report the selected 5.6% for low risk in the sales report at top, page 16, but this cannot be part of the more inclusive allele plot. They instead have reported good but not comparable info at 6 years. (21% pts below 1% allele)

I of course hope we see a different result in our real patient experiences, with plenty of self interest too.

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PEG 6+ year

[monarch5000 in reply to EPguy]

See the 10:34 mark in this 2016 video about PV patients in a PV1 study that were middle aged and 70% had been given Pegasys interferon as a first line therapy: youtu.be/vuhwGEi4Y_k(Not working as expected?) Note that for 6 years there were no major problems with loss of drug efficacy, intolerance, blood clots, vascular events or disease progression to myelofibrosis or acute myeloid leukemia. All these tremendous benefits of early diagnosis and prescribing Pegasys as a first line therapy at the time of diagnosis were known back in 2016, yet ignored by most MPN specialists in the USA and the U.K. because the findings of the PVN1 study were not based on a formal randomized clinical trial.

[EPguy in reply to monarch5000]

Good presentation. One surprise is he said ~30% of pts were still on IFN after ~7 years (6:00) for all 3 studies. Of the 70% that were off 38% in the French (FIM) study were in CHR and didn't need it any more. This is not common practice today, but quite appealing. But other reports have losing MR if IFN stays off.

27% discon for toxicity. If they make it thru the 1st or 2nd year, it's likely to be ok, this is the slide you show above.

30% had complete MR at 4 years in FIM. (0.5% allele) He said it further CMR is unlikely after 4 years. Ropeg had 21% after 6 years (1% allele,) MD Anderson had 18% CMR. These numbers seem to correlate to patient risk profile.

***Big news: Higher dose esp in 1st year increases MR. This is the 1st time I've seen such a report. But the relevant slide is censored. Other reports have shown little connection, but have not focused on high dosing the 1st year.

He also notes the familiar correlation of CHR to MR.

In the 3 studies there were better results with lower risk pts, a key lesson from this thread.

Qualifier on this report is the 2016 date, a long time ago in this business.

[monarch5000 in reply to EPguy]

PharmaEssentia is also beginning to see the same benefit of high dosing during the 1st year for the subset of patients that need them and can tolerate them due to having more aggressive disease (high phelbotomy requirements).

Below at the 1:14 mark, Dr. Raymond Urbanski, Head of Clinical Development for PharmaEssentia, explains why the Company favors rapidly increasing the dose during the first 4 months of treatment (he accidentally says 4 weeks in the video) because they will usually more reliably achieve normalized blood counts and a sharp drop in the allelic burden. youtu.be/FtvJQ-UxzQA(Not working as expected?)

[EPguy in reply to monarch5000]

Thanks so much for the link. He does have an interest in Besremi, but so do many of us.

He claims durable HR. Says it need to work up to 15 years, but the data go to only 7.

-The China and Korea data are new and support aggressive titration. (12-24 week time frame) 250-350-500 in a 4 (month) span give quite an impact on VAF.

-Many of us would be flattened by that schedule. I for example would have almost no blood cells left and probably would be housebound at best.

Tempting morsel he offers: ASH 2023 will provide the data he's talking about. I hope there is more insight on the CHR/MR connection. If we get CHR just fine at 100 do we need that 500 for MR? The idea might be titrate fast to whatever dose gets CHR, don't let HR lag once starting Bes.

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Still missing is the orange line in my plot way up in this thread. They now have 7 year data he said, so they have, and aren't sharing, that plot out to 84 months. We've figured here that line is very risk dependent.