Anemia caused by chronic kidney disease can be treated with injectable drugs that belong to an older class of drugs. Akebia Therapeutics is committed to making pill formulations more convenient for patients reject The FDA has raised safety concerns about the drug vadadustat. The regulatory decision echoes last year’s rejection of a competing anemia drug from the same new drug class.
According to Cambridge, Mass.-based Akebia, an FDA letter it received on Wednesday indicated that vadadustat failed to demonstrate that patients faced a risk of major cardiovascular events roughly comparable to that of darbepoetin alfa, which was tested in Phase 3 Older clinical trials of injectable drugs. The agency also noted that patients on dialysis had an increased risk of blood clots and an increased risk of liver damage. In order for vadadustat to demonstrate that the benefits outweigh the risks, the FDA’s Complete Response Letter (CRL) indicated that Akebia would need to conduct another clinical trial.
“The CRL announcement was surprising, especially for the dialysis patient population,” Akebia CEO John Butler said on a conference call Wednesday night. “The dialysis data from our global Phase 3 clinical development program are clear and consistent. These trials met the primary and secondary efficacy endpoints, as well as the primary safety efficacy endpoint.”
Vadudstat is a so-called hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. This class of drugs mimics the effects of high altitude on the body’s oxygen supply. The body responds to hypoxic conditions by making a protein that stimulates erythropoietin, a hormone that in turn triggers the production of oxygen-carrying red blood cells.Negative regulatory decision on vadadustat follows FDA rejects Last August, roxadustat, a FibroGen drug also developed to treat anemia caused by chronic kidney disease.
Akebia has tracked regulatory reviews of FibroGen drugs, which, according to Butler, have not been consistently evaluated by the agency. He said Akebia read an FDA briefing document prepared for a roxadustat advisory committee meeting to convey that comparing percentage differences in adverse events could be deceptive, and would prefer to look at the rates of those events.
data post It was shown in the New England Journal of Medicine nearly a year ago that while vadadustat met its primary efficacy goal, it missed its primary goal of assessing cardiovascular risk. The results showed that more patients in the vadadustat group experienced adverse and serious vascular events. But Butler added that the rate of thrombosis was the same in the vadadustat group and the comparison drug.
“It’s very reassuring to us that we’re looking at it the right way and don’t see a difference and we’re going to have a clear path forward,” Butler said. “But with different commenters, you’re going to be different. different, possibly different appearances. It’s difficult when methods don’t have this consistency.”
Despite the FDA’s request for a new trial, Butler said it’s too early to say whether this is the next step for vadadustat. The company plans to discuss the matter with the agency after speaking first with partner Otsuka Pharmaceuticals, which has agreed to share the development and commercialization of the drug in the U.S. The Japanese pharmaceutical company has also spearheaded the development of the drug in a number of other regions around the world; it has already A marketing authorization application was filed in Europe for the treatment of anemia in adults with chronic kidney disease, including both dialysis-dependent and non-dialysis-dependent patients.
Butler believes that if roxadustat is any indication, vadadustat’s prospects in the EU are good. In addition to being approved in the UK, China, Japan, South Korea and Chile, Fibrogen’s drug is already approved locally.
“We think we have a good simulation because roxadustat receives a CRL with well-known data, but they are approved in Europe for dialysis and non-dialysis patients,” Butler said. “Given the very different approach that the EMA appears to be taking through the FDA, we would expect very different outcomes.”
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