News on new MF therapy Momelotinib

[EPguy]

I just saw in the business news that Glaxo Co is buying an MF drug maker, Sierra Oncology, for its new drug Momelotinib. Implication is Glaxo expects FDA approval. I never used to look at these things, but MPN stuff gets interesting when you've got the Dx of one.

Momelotinib failed its first round trials against Rux, but in the context of anemia it's looking good enough for Glaxo to spend $1.9 billion on it.

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As I understand it, MF complications include low PLT and anemia and thus transfusion dependence. Two new agents, just-approved Vonjo and potentially approvable Momelotinib will address these issues, PLT and anemia respectively. Comments welcome from those who understand MF better than I.

The quotes below summarize some features. The report linked here is very detailed on the new agent.

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There are recent posts on Vonjo, (pacritinib), just FDA approved for MF with low PLT counts (severe thrombocytopenia). The new Momelotinib is focused on MF with low iron (anemia) According to this report <<In MF patients, disease-related anemia can be exacerbated by treatment with ruxolitinib because of myelosuppression>> And MF patients already have or very likely will get anemia.

Momelotinib reduces transfusions <<In the 7-year follow-up study of 100 MF patients treated with momelotinib at the Mayo Clinic, 51% of the patients achieved transfusion-independence, and 44% had improvement in anemia>>

<<...the two SIMPLIFY studies revealed additional OS advantages for patients who achieved transfusion-independence >>

<<,momelotinib is minimally myelosuppressive and, along with pacritinib,(Vonjo) could help patients with “cytopenic/myelodepletive”>>

Momelotinib suppresses Hepcidin in the body to do its magic. Hepcidin is also relevant to PV, where Resfurtide is likely to be approved to reduce phlembotomies. (discussed in older posts) No direct connection except that hepcidin is getting lots of attention.

jhoonline.biomedcentral.com...

[hunter5582]

All of the above was touched on in today's MPN forum put on by MPN Advocacy & Education International. The day was very interesting and informative. It was great to have the chance to be there live. Also to have the chance to talk to Industry Sponsors from PharmaEssentia, Imago, Incyte, and more. Hope to see you and others from this forum at one of these events someday.

[EPguy in reply to hunter5582]

My very late west US coast schedule makes it not possible for me, based on the times they seem to happen. But if there are recordings that is always good to see.

Transcripts are also good if such exists, quicker to absorb than video.

[hunter5582 in reply to EPguy]

I do believe the recordings will be posted, Will keep an eye out for them. Hopefully there will be a West Coast event soon.

[Meatloaf9 in reply to hunter5582]

Very happy that you were able to attend this conference. Please post if you learn of any videos or transcripts of the meeting. What would you say was the biggest take away from the conference for PV patients? I assume ET and MF patients would also like to know of any information for their conditions. Thanks for all you do for this forum.

[hunter5582 in reply to Meatloaf9]

There was a lot if information presented. Most of it was a really good summary of what we have been tracking in the literature, adding to the depth of understanding. It was also helpful to hear from the industry reps about what is going on with their medications and what is emerging. The session on Genomics could have been an all-day presentation all by itself. The short version is "genomics matter."

There was an entire presentation just on managing PV. I will post it when it is available. There is quite a bit happening in treatment options for MF. I have not been tracking that as closely so some of that was new for me. There was some discussion of clinical trials for ET - Besremi and Bomedestat.

While no details were given, there is work underway regarding dose titration for people with PV using Besremi. PharmaEssentia is aware how disturbed many of us are about wasting the medication. It sounds like they are already aware that many of us will be staying on doses much lower than 500mcg. They are still sorting this out. One of the issues is that the delivery mechanism for Besremi also has to be FDA-approved (not just the drug itself). More to come on this.

All the best.

[Meatloaf9 in reply to hunter5582]

Thanks for the update. Looking forward to the managing PV info as a PV sufferer. Also will be interesting to see info on genomics, it seems it is playing an ever increasing role in treatment guidelines and prognosis. Thanks again. Best to you.

[EPguy in reply to hunter5582]

For Bes dosing, is there any indication they are watching our discussions? Plenty of info right here. Still curious how the trial patients endured 500 so well.

Interesting they discussed the delivery problem. I've posted before one reason for FDA rejection of Bes Mar '21 was "administration" instructions. (another reason was problems getting to Taiwan during Covid for inspection)

targetedonc.com/view/fda-is...

<<Additionally, the agency also noted that additional data are needed regarding the administration format for the product.>>

I think the dosing system we have now was hacked together to get thru this rejection. We would be better to have the Euro type, for those who have not seen it, here it is. My guess is FDA found ti too complex for US.

Note they allow more than one use of it:

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

<< At doses up to 100 micrograms, the same pen can be used twice. >>

Bes Pen Euro

[hunter5582 in reply to EPguy]

They went with a KISS approach that would allow everyone to be able to get their dose, from 50 - 500. It was a pretty brief conversation, but my impression was that they did just take the simple way at first to get it approved and are now working on a more sophisticated approach. I believe they are also working to better understand dose titration in the real world. Looking at the doses we are really using in practice.

It will be a learning journey for us all.

[Barbiebreath]

I really appreciate all the information that you and Hunter find and report to us. Thank you. 😃

[3cance]

I just recently started on Vonjo. The increased fatigue and symptoms of MF are very difficult for me. I was glad to read the information here. It gave me hope of seeing improvement in the number of hours I can have with less fatigue.

[EPguy in reply to 3cance]

I relate well to fatigue. Not from my PV, but from a different condition acquired via vaccine with IFN (see my post "Last Dose" if interested.)

I describe fatigue of this sort (in context of Sjogren's) as "fatigue can be paralyzing and impacts nearly all patients. It is not “being tired” nor is it remedied by rest, lifestyle changes or other familiar antidotes to being tired."

MF fatigue likely is very similar. If Vonjo helps that would be wonderful.

[3cance]

Your description of fatigue, ‘ “I describe fatigue of this sort (in context of Sjogren's) as "fatigue can be paralyzing and impacts nearly all patients. It is not “being tired” nor is it remedied by rest, lifestyle changes or other familiar antidotes to being tired." ‘ is a very good description of what I live with every day. There should be another word to describe this type of fatigue. It is as bad as dealing with pain issues I have had from DJD, Arthritis, fibromyalgia and surgeries. It is a crippling fatigue that I seldom get relief from. Thank you for understanding.