Romiplostim Classification and Mechanism of Action


Ivy Altomare, MD: So it is now the 10-year anniversary of the approval of romiplostim for chronic ITP [immune thrombocytopenia], which is shocking to me. We think of them as new agents and they’ve been around for 10 years. I know that you were one of the key investigators that was on the initial New England Journal of Medicine paper for romiplostim, is that correct?

Ralph V. Boccia, MD, FACP, LLC: That’s correct. We were PIs [principal investigators], basically. And remember there were 2 studies, and this will get back a little bit to what we were talking about before.

Ivy Altomare, MD: I’m so sorry to interrupt you. So romiplostim is a TPO receptor agonist, a thrombopoietin receptor agonist. Can you talk about that class of drugs and what the mechanism is?

Ralph V. Boccia, MD, FACP, LLC: We know that thrombopoietin receptors, or MPL receptors, are both on macrophages; I don’t mean macrophages, I mean megakaryocytes.

Ivy Altomare, MD: I make the same mistake all the time.

Ralph V. Boccia, MD, FACP, LLC: We’ve been talking so much about macrophages. Anyway, on both platelets as well as on megakaryocytes. And the native endogenous hormone to both induce production maturation and proliferation is thrombopoietin, constitutively produced mostly in the liver, stimulates the production of platelets by megakaryocytes. And so we have the ability now to target that in the case of 2 drugs that are on the market and 1 probably on the heels of being released. Romiplostim, which is a peptibody, is a platform that Amgen has developed where they can develop a protein or peptide that can attach to and activate any receptor. And then they hook on to that an antibody that gives it durability and duration of action in the bloodstream.

So we have one TPO-mimetic agent that’s parenteral and that’s romiplostim with a peptibody, and the other is eltrombopag, which is a small molecule and attaches to the transmembrane receptor. So a little bit of a different position of activation, but both activate the TPO through the JAK/STAT [Janus kinase/signal transducer of activation] pathway to produce platelets through megakaryocytes. The drug was developed in 2 parallel identically designed, multinational double-blind, double-dummy studies.

Ivy Altomare, MD: You’re talking about romiplostim.

Ralph V. Boccia, MD, FACP, LLC: Romiplostim. One in patients who had been splenectomized and another in patients who still had their spleens. And the results were that between 80% and 90% of patients had a sustained response. And all of the trials are done with all of these agents used as the target platelet count of 50,000 or higher because that’s considered the safe platelet count at which point patients generally don’t bleed unless you invade them. So, again, about 90% of patients, 80% to 90% of patients in both arms, a little bit lower in the splenectomized patients, but they had a longer duration of disease than the nonsplenectomized patients for obvious reasons. But between 80% and 90% of patients would respond, and when we took it 5 years out with the extension, there was no new safety signals and there was no loss of efficacy in those 2 trials.

Ivy Altomare, MD: And I’m sure you, as I do, have patients that have been on these agents for years with continued response.

Transcript Edited for Clarity

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