Whilst I’ve been on Pegasys and Besremi I’ve been asleep at the wheel regarding new potentially game changing drugs. Now that I’ve had to switch to Ruxo I’m more focused on other options if/when Ruxo stops working.
I know there are quite a few new drugs becoming available but as far as I can tell there is nothing as potentially disease modifying as interferons? It seems most of these new drugs are effectively similar to Ruxo (and can replace Ruxo) but are perhaps more effective re anemia/spleen etc. But not disease modifying?
Is anyone aware of anything that we can get excited about! There was a lot of interest in combo therapies but has this gone a bit quiet?
For those of you on Interferons, combining with statins could be very beneficial according to Dr Hasselbalch (I may have misspelt that!)
Best wishes Paul
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Paul123456
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I’m excited to see results for the new type 2 Jak2 inhibitors. Specifically, I’m most interested to see some results for Incyte’s newest Jak2 inhibitor. I believe it’s in trial now and other medical institutions are also recruiting patients to begin this study. I believe it’s only available to MF patients at the moment, but I’m sure this will be expanded to other patients with MPNs if determined to be safe and effective. What is interesting is that this drug is specifically supposed to be able to target only mutant Jak2 and leave the wild type Jak2 alone. So basically it is a selective Jak2 inhibitor. Hopefully we have good results!!
Interesting. I'm calr with 1% jak2. I was on interferon for 7 months but it went rogue and attacked my heart resulting in heart failure. Happens to 1 in 100,000 apparently, lucky me. Not on anything at present with platelets at 998.
Don't forget that Rux is now known to be disease modifying for many as seen here and recent reports and posts. I've posted my continuing VAF decline on it.
There are at least three new drugs in trials or just about to be. You're right they all are small molecule inhibitors like Rux. Rux is a type 1 inhibitor, meaning it targets Jak2 only in the active config. Rux also targets Jak1 by design, I think it's therefore helping my Sjo, but this extra target may be one reason for Rux's extra immune suppression.
The Rux+ drugs you refer are still type 1's as far as I know. There are largely for MF pts not responding, or over responding, to Rux
Type 2's target both active and inactive, hence reach deeper into the clone. But the types 2's of the 2010's were duds. Now there are some looking promising. But at least one is not a type 2, rather a whole new thing that is specific to v617f, as Walshman notes.
These are in trials for MF. One planned for PV targets just Jak2, but they have not claimed it's specific to the clone.
Manouche has posted these reports and I have done some deep looks into some. I've been hoping to make a fresh top post putting it all together. Meantime you can find some details including in my prior posts scattered about.
Hi I am starting a Phase 1 study in Canada from an Incyte drug INCA 33989-101 administered as a monotherapy or in combination with Ruxôitinib in participants with myeloprôiferative Neoplams
This study is for people with CALR mutation ET or myelofibrosis.
Me I have ET CALR Type 2.
We are 80 in the world so far on this study.
I received my first dose last week and already my platelets decreased of -200 from starting.
It’s an IV drug 2 times per month. We are right now at the maximum escalation dose which is 2500mg.
Let me know if some of you are on it. Seems very promising it is a monoclonal antibody against the CALR mutations
Here is the press release from Incyte: (Incyte make Rux, with its patent expiring soon, so they are working on several new therapies.)
"INCA033989 binds with high affinity to mutant CALR and inhibits oncogenesis, the process of cells becoming cancerous, in cells expressing this oncoprotein. As described in our presentation, INCA033989 potently antagonizes CALR oncogenic function, resulting in selective inhibition of JAK/STAT signaling only in CALR-mutated cells with no effect on normal, non-oncogenic cells. This selectivity of action with INCA033989 results in the specific killing of tumor cells harboring the mutation and is suggestive of the potential to alter the course of disease in patients with CALR-mutant MF and ET"
It's one of a growing line of therapies that directly target CALR.
Hi Paul, I am currently one month in on the phase 3 trial of Bomedemstat. It’s an Lsd1 enzyme inhibitor hopefully therefore inhibiting platelet replication. This trial is for those of us intolerant to hydroxyurea, as I was. I am ET Calr type 1.So far my platelets have reduced to 660 from 900. They haven’t been that low for over three years. Apart from some altered taste sensation in some food and drink, no side effects. This drug also appears to have some effect on allele burden . I’m feeling very positive about new drugs like those for all MPNs and MF. There are more in the development pipeline.
It is very nice to hear that there is another PV patient taking Bomedemstat. At some point we were only two and then I think I was the only one probably worldwide. I started taking it on July,2022, so safety wise I think it should be fine. In my particular case the drug lowered the platelets to 110-150 values from 1million. It has not controlled HTC as I would have expected it, but it did lower some MF that Drs were starting to see from MF1-2 to MF0. Also there has been a reduction in jak2 alele burden. So, in general I think it is a great outcome taking into account I was feeling very lightheaded and dizzy all the time. I do have some nausea that I have been managing it with ginger ale and eating every 3 hours. Make sure you watch out for neutropenia though. First couple of months might be a roller coaster in terms of finding the right dosis but then it should be smooth. I really hope that the drug works for you and that it ends up being a disease modifying therapy that we can all benefit from.
Your experience points to a third option, adding to Rux and IFN, for disease modification for some pts. That is exciting. You're right it's not designed so much to control HCT. Maybe it will be esp effective in a combo with IFN or Rux, or even HU. And we await Rusfertide and others in line to directly control HCT.
assuming you are still PV there is no evidence that Rux loses effectiveness according to expert at Mount Sinai when I was there in Oct. For some it can reduce AB and in my case BMB recently showed considerable improvement and little evidence of PV as opposed to BMB in 2017 on venisection only. As with the interferons the important bit is it can do these things for some, not all.
Thanks, you may be right if PV and this article is quite historic but…
‘However, even patients with a good initial response may lose response to ruxolitinib after 2–3 years of therapy [25–28]. In the phase III COMFORT-I [24] and COMFORT-II [23] clinical trials, approximately one half of patients discontinued ruxolitinib within 3 years and three fourths did so by 5 years [25, 26].20 Mar 2020’
The Comfort trials were for MF. There has been an average time limit on Rux's success in MF, anemia being a particular tolerance problem. So Rux acquired a broad reputation for short efficacy of ~3 years. There are now several newer Jak-i's for MF that address low PLT and low reds after Rux therapy.
But the time limit seen for MF has not been common with PV, as ainslie says. I asked my MPN Dr a couple times, he has Rx'd Rux for over 10 years for PV, and says the typical pt has good long term response.
The Response and Majic Rux trials were for PV, and both showed disease modification or many pts. One trial had data to 12 years as I've posted.
But all are meds have issues including various reasons to be forced off therapy. So we always need better ones. The Bomedemstat results in this thread are exciting to hear from real pts.
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Two side effects from Pegasys
