ASH 2024 | Findings from the MATTERHORN trial investigating roxadustat in LR-MDS

Yes, the MATTERHORN trial was a trial that I was privileged to be the leading author. And this was Phase III clinical trial which tested the efficacy and toxicity obviously and safety of roxadustat. Roxadustat is an oral agent which was an agent of FibroGen company, the mechanism of which is again a different mechanism. This is a hypoxia inducible factor, prolyl hydroxylase inhibitor. In simple words to people who are not really would like to dig into this complex mechanism, I would say that this is an agent which interferes in the erythropoiesis, in the production of red blood cells and the place where it interferes is different from all other agents. All other agents to treat anemia, erythropoietin, luspatercept, now imetelstat, act in various mechanisms and roxadustat acts in a different mechanism which I just now mentioned. The first one, the Phase I and Phase II trials were very successful again showing something like 40 to 50 percent response rate and improving the anemia and the MATTERHORN which we are talking about was a Phase III clinical trial. In this trial we compared the efficacy and safety of roxadustat in transfusion dependent patients. Most of them were erythropoietin resistant. And unfortunately, the primary endpoint was not met. In other words, when there was an interim analysis made, we found that the response rate was 47%, which was exactly like they expected. However, the placebo arm had a response rate of 33% and the difference was not statistically significant. So it made the company to declare and announce that the study failed and from now on the development has been stopped. I think that it’s a shame. I am very sorry for that because I don’t think that the study failed. And the reason for not thinking so because if you take only the subset of patients who had high transfusion burden, you can clearly show that those patients who had higher transfusion burden indeed benefited from the drug significantly more than the placebo and we published it in the paper which was published in American Journal of Hematology. Moreover, if you test those who had hemoglobin rise of more than 1.5 gram per deciliter, which is considered a significant hemoglobin increase, again, it was significantly better in the roxadustat-treated patients compared with the placebo. And finally, I can tell you about some of my patients, especially a patient which was really odd, but you know, you cannot ignore it. A patient who started the study with hemoglobin of 7.5, transfusion dependent. And after several weeks, hemoglobin was 14. And she obviously did not require any blood transfusion. And I’m not aware of any placebo that does it. So in summary, officially the MATTERHORN trial failed. And unfortunately, as of today, there is no further development of the drug, which is a shame. I think that the study did not fail. And I think that the drug works. Maybe not in every patient. Maybe not all the time, but it works. And I hope for the patients that at some point, maybe in the near future, someone will take it and the development will be renewed for our patients who really need treatments.

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