番茄社区

Roxadustat is now under FDA review for treating anemia of chronic kidney disease, in both non-dialysis-dependent and dialysis-dependent patients, with a PDUFA date of Dec. 20, 2020.

In this 番茄社区 video, , of St. John Hospital & Medical Center in Detroit, and principal investigator in clinical trials for roxadustat, explains why the availability of the first orally administered, small-molecule hypoxia-inducible factor prolyl hydroxylase will have a great impact on our CKD patient population.

Following is a transcript of his remarks:

So for the last 30 years, we have had available for the treatment of anemia in chronic kidney disease erythropoietin, which has been very effective, but not without its shortcomings. Specifically, in high doses has been associated with poor cardiovascular outcomes. Recently, a lot of focus has been shifted toward HIF-PHIs, and what that stands for is hypoxia-inducible factor proline hydroxylase inhibitors. Now that's a mouthful, but basically, these small proteins take advantage of a normal physiologic process within human beings that when confronted in a hypoxic environment, for example high altitude, our body produces more erythropoietin. So basically these small protein molecules inhibit a proline hydroxylase creating in a normal oxygen environment what the body views as a low oxygen environment. And what it does is it increases endogenous erythropoietin. It improves iron regulation, and it reduces hepcidin, which is basically an inflammatory agent within chronic kidney disease patients. So it's really a fascinating cascade of a normal physiologic process.

So over the last several years, we enrolled approximately 10,000 patients with chronic kidney disease, both on dialysis and not on dialysis, and studied the effects of roxadustat, which is an oral hypoxia-inducible factor. What we found was fascinating, first and foremost, roxadustat was effective and safe in all patient cohorts. So those are patients with chronic kidney disease, not on dialysis, patients on dialysis during the incident period, which is the first four months where we see very high mortality, and then prevalent dialysis patients. Those are patients on dialysis for greater than four months.

We found that roxadustat was effective, whether or not patients were iron replete or not iron replete. And that is really, really important because the current standard of care, when we use Erythropoietin requires fairly high, consistent doses of IV iron. We found that cardiovascular safety was non-inferior in the non-dialysis population, but interestingly in the dialysis population we found that the incidents of MACE and MACE+ in the incident dialysis population was significantly lower than epoetin alfa, which was the active comparator arm, 30 and 34%, respectively. And in the prevalent arm, the incidents of MACE+ was 30% lower. So that was a very, very interesting finding because we have a big focus on these cardiovascular endpoints in our very sick population.

Additionally, we found that the transfusion requirements was significantly lower in the roxadustat treated patients, whether they were on dialysis or not on dialysis. So, again, our big push is to transplant patients, preemptively and avoiding a transfusion, obviously avoids aloe sensitization and the forming of antibody levels that might preclude a transplantation.

I don't want to underestimate the importance this is going to have on our patient population. Currently on CKD patients, not on dialysis, it's very difficult to treat them with subcutaneous erythropoietin. Roxadustat is an oral agent. So I'm thinking that more patients are going to have access to having their anemia managed with an oral agent than they have in the past with a subcutaneous agent. Additionally, the lower iron requirements, we hope will preclude these patients from requiring another trip to get IV iron supplementation. So, we're really pleased, roxadustat has been available in China and in Japan for about 18 months, a hundred thousand patients have been treated. And so far the data continues to look really good. So we're excited for this opportunity in the United States to really change how anemia of chronic kidney disease is treated moving forward.

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