ASH 2020 | Sotatercept: novel therapy for MF-induced anemia

This is an investigator-sponsored trial that we’re doing at MD Anderson. It’s just us. And this has been actually going on for a few years and frankly serves as the basis for Celgene and BMS’s decision to explore luspatercept in this area. So let me clarify a bit, shed some light on these drugs. There are novel class of drugs, so sotatercept is actually the first in class. So these drugs, sotatercept and luspatercept, they are what is called active in receptor-ligand traps. So these drugs basically trap or sequester ligands belonging to the TGF beta superfamily that bind to the activin receptor. So by trapping those ligands, they prevent their binding to the activin receptor and thereby prevent the downstream signaling, which goes through the SMAD pathway, et cetera.

So ultimately what these ligands do is that they suppress or inhibit the terminal stages of erythropoiesis. And if you trap or sequester these ligands, you help promote erythroid maturation by removing that inhibitory influence. So that’s the mechanism of action. And like I said, it sort of began with sotatercept and since then luspatercept has been taken forward in this space and is already FDA approved in beta-thalassemia and MDS with also encouraging results in myelofibrosis from last year’s ASH. So coming back to our study with sotatercept, the two drugs are very similar. So with our study with sotatercept, we had three types of patients, those who don’t require any transfusions, those who require transfusions here and there, you can call that occasional and those who are frankly transfusion-dependent by formal criteria. So we allowed all these patients and then we had two cohorts.

One in which sotatercept was used alone and one in which it was added on to patients who have been on ruxolitinib but a stable dose and are anemic, or requiring transfusions like I was just saying. So this is the two cohorts and overall bottom line, our response rate is around 30%. Right around 30% for both the cohorts. Actually, the actual numbers are just slightly different from that in the abstract, but right around 30% for both the monotherapy sotatercept alone and the sotatercept added to ruxolitinib. And remember when I say response rate, I’m talking about a composite response rate that includes both anemia responses and transfusion independent responses. So we had both types of responses, actually. In our combination cohort, all the responses were anemia responses. Whereas in the monotherapy cohort, we had responses both in anemia and in transfusion independence. And again, sort of goes without saying, but for the transfusion-dependent patients, a response meant becoming transfusion independent.

And for patients who are just anemic or requiring occasional transfusions, for them a response meant getting a one and a half gram increase in hemoglobin sustained over 12 weeks. This is pretty standard. And yeah, so the toxicity was very good. It’s a very well tolerated drug. I mean, really no major concerns regarding that. So I think it’s just another potential weapon in the armamentarium for anemia in myelofibrosis, which is a difficult area. Currently, we use things like danazol, low-dose thalidomide or ESAs. And so this class of agents can prove a very useful new edition in that regard.