New Drug may be relevant to MF, ET

[EPguy]

A new drug for pulmonary hypertension, (PAH) Sotatercept, has just been approved. PAH is not a typical MPN worry, but it has side effects that may be relevant to MPN. It can increase Hb and decrease PLT. These are listed as adverse effects in the label.

Some researchers made the MPN connection. In this phase 2 trial they found some MF pts had a benefit for anemia. This could allow MF pts to stay on Rux for longer, esp those not requiring transfusions. Strangely they did not track PLT at all.

ashpublications.org/blood/a...

"Sotatercept is safe and effective against anemia of MPN-associated MF, both in non-TD and TD pts, with a response rate of 30% when used alone and 32% when used in conjunction with a stable dose of rux. All responses in the rux cohort occurred in non-TD (transfusion dependent) pts. "

Its other side effect "Severe Thrombocytopenia" could be useful for ET pts who are not responding to other options.

accessdata.fda.gov/drugsatf...

Not likely useful to PV given the Hb effect, but the wording of the label implies the PLT effect is esp strong. The ET application is intriguing since there are no good solutions for PLT reduction beyond the familiar agents we know. But there are no studies I can find on this use.

It would be off label for MF and ET, but at least the MF indication has evidence of effectiveness, so insurance might pay.

I learned of this from the Sjogren's forum where PAH is often seen. But the MPN connection came to mind.

[hunter5582]

Very interesting. I believe there is an emerging consensus that combination therapies will be more common until a true cure is found.

[Joetcalr]

Wow, very interesting.

Is it known about in the MPN field?, It sounds a possible for me! I’ve low haemoglobin and high platelets and hydroxy is making me feel tired all the time. Diagnosis of ET/PMF – unclear which.

However I’ve already got low blood pressure, I wonder how that would be affected?

Thank you for highlighting it.

[EPguy in reply to Joetcalr]

It is known for MPN, the study linked above is regarding MF. If you have MF that trial could be a basis to discuss with your Dr. You're right at least on first look your Hb and PLT match its effect. But I find no explicit reports on actual PLT data.

In this report it has a low risk of increased BP (3.5%pts):

"Adverse events noted with sotatercept included epistaxis and gingival bleeding, telangiectasias, thrombocytopenia, increase in hemoglobin level, and increase in blood pressure."

acc.org/Latest-in-Cardiolog...

All the effects you seek are in there, along with some others. A careful consult with your Dr seems worth a try.

[Mishie14]

thank you very much for sharing. This is an interesting read about another drug combo that could be available to help us. I appreciate very much being able to learn more about what’s going on in the world of MPN.

I hope you are feeling better, finding some relief. I read up on Sjogrens after your previous post. It’s a very nasty condition. I admire your strength and courage to face it head on. Stay safe.

[EPguy in reply to Mishie14]

For now MPN pts would need to pursue it as I don't think it's in clinical use for MF yet, and the ET potential as not been tested as I don't think the MPN field has made this connection yet. But for ET pts out of options it could be worth a Dr discussion.

Thanks for the kind thoughts. Right on the Sjo, it's an evil disease that blends all the rheumatoid diseases as one and throws in sicca to ensure misery. But its severity is known only to those who look deep (this includes many rheum Drs) It is known to associate with IFN use and separately IFN in the body, so watching for any A-I's while on IFN is important.

[jointpain]

If only you had said Portal hypertension, then this could be very suitable for my wife. We have no idea if she has pulmonary hypertension, but as she has oesophageal varices due to her Portal vein thrombosis she had a couple of months after her Splenectomy and diagnosis of MF, it may be worth asking her consultant about.

[EPguy in reply to jointpain]

Portal HT can be an MPN condition while PAH is associated with my other condition. I agree maybe this agent can help portal, a well knowledgeable dr might be able to say whether there is potential.

[jointpain in reply to EPguy]

Just read that NICE here in the UK are assessing this drug " What comes next is that NICE (the national body that makes treatment recommendations) will do an appraisal of the drug, starting in March next year (2024) and that will take a number of months." So it's not yet available unless you are in a trial.

[jointpain]

Hi EPguy, tis me again, just checked pulmonary hypertension symptoms, and everyone of them applies to my wife, for a week or so after she's had a couple of bags of packed red blood cells, which has happened three times this year already.

[EPguy in reply to jointpain]

Pulm HT is a serious deal, well worth a Dr discussion and maybe this new drug. But if its only after transfusions maybe other factors are worth checking.

"Pulmonary arterial hypertension (PAH) is tough to diagnose. Its symptoms can mimic other, less serious conditions. "

webmd.com/lung/pah-diagnosis

A pulmonologist would be a good start.

[JustKeepSw1mming]

Thank you very much for sharing!! Very interesting. Good to see new options are becoming available.

Take care if yourself and all the best