Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 478: A Phase II study of sotatercept (ACE-011) in myeloproliferative neoplasm-associated myelofibrosis and anemia
3:12 minutes.
TRANSCRIPTION:
DR STEENSMA: There are 2 drugs that modulate signaling through activin receptor 2. Sotatercept inhibits activin receptor 2A. Luspatercept inhibits activin receptor 2B. There are a number of molecules like transforming growth factor beta and GDF11 that signal through these molecules. And that may inhibit red cell production, may inhibit erythropoiesis. And so in MDS, we’ve seen trials with both sotatercept and luspatercept. The sponsor decided to move forward with luspatercept, because there was a very good response rate — actually with both of them, but luspatercept, for commercial reasons, they decided to move forward. And there’s an ongoing randomized, placebo-controlled trial in MDS with luspatercept that hopefully will lead to registration of that drug in MDS with ring sideroblasts. DR LOVE: And these are fusion proteins? DR STEENSMA: They are. They are ligand traps. So basically they’re fusion proteins that bind to all of the things that normally would bind to the activin receptor 2, AR2B. DR LOVE: So I guess we’ve heard about aflibercept, the anti-angiogenic agent in colorectal. It has the same ending. But the same kind of soaking up the ligand thing, huh? DR STEENSMA: Correct. It’s similar to etanercept, which binds to tumor necrosis factor alpha and which is approved for rheumatoid arthritis, does virtually an identical thing. It’s just a different family of inflammatory cytokines and red cell inhibitory cytokines. So this was a study in myelofibrosis patients who had anemia, using sotatercept. And we don’t do great with anemia in myelofibrosis. We have ruxolitinib, which works well for shrinking the spleen and improves some of the constitutional symptoms. But when it comes to anemia, we use things like androgens or thalidomide and prednisone. And they help some patients, but we definitely need more drugs that are going to improve the red cell production in patients with MF. And so this was a study of 18 patients. And they received the sotatercept with injections every few weeks. And a few of them did have responses. It was 5 of the 14 evaluable patients, 36%, had an improvement in their hemoglobin level. One great thing about sotatercept and about luspatercept, incredibly well tolerated, very, very few adverse events from these drugs that we’ve seen in studies thus far. And, in fact, sotatercept is being moved forward in osteoporosis and in benign hematology conditions to try to improve bone density and anemia, respectively. |