FibroGen presented data from two pooled analyses from its roxadustat global Phase III development program this weekend at the American Society of Nephrology Kidney Week 2020 Reimagined conference.
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FibroGen presented data from two pooled analyses from its roxadustat global Phase III development program this weekend at the American Society of Nephrology (ASN) Kidney Week 2020 Reimagined conference. The analyses looked at associations between the hemoglobin (Hb) levels achieved and cardiovascular outcomes in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients with anemia of chronic kidney disease (CKD).
They analyzed six total trials, three in NDD patients and three in DD patients, and they showed that Major Adverse Cardiovascular Events (MACE; all-cause mortality, myocardial infarction, and stroke) and MACE+ (MACE plus heart failure or unstable angina requiring hospitalization) rates were highest when Hb was less than 8 g/dL, decreased as Hb rose, and were lowest when Hb levels exceeded 10 g/dL.
“We have evidence that roxadustat is effective in increasing and maintaining hemoglobin levels in patients with anemia with chronic kidney disease, as shown across the roxadustat clinical program,” said Robert Provenzano, associate professor of Medicine, Wayne State University, Detroit, and primary investigator in the roxadustat global Phase III program. “These new post-hoc analyses showed that for patients who were treated with roxadustat, rates of cardiovascular events were lowest in patients when their hemoglobin levels were greater than 10 g/dL. These additional safety results, coupled with roxadustat’s well-defined efficacy profile and its oral formulation, support the potential for roxadustat to become a safe and effective treatment option for anemia of chronic kidney disease, an area that has seen little therapeutic progress in the last 30 years.”
CKD is typically a progressive disorder marked by gradual loss of kidney function that can lead to kidney failure or end stage renal disease (ESRD) that can require dialysis or a kidney transplant. It can occur in about 10-12% of adults globally and is expected to become the fifth most common cause of premature death around the world by 2040.
Anemia is a common early complication of CKD and affects about 20% of CKD patients. Although blood transfusions are treatment for severe anemia, they can decrease a patient’s chances for kidney transplant and increase potential infections or complications like heart failure and allergic reactions.
Roxadustat is a first-in-class, oral small molecule HIF-PH inhibitor. It promotes the production of red blood cells and improves iron absorption, transport and mobilization. The drug is already approved in China for anemia in adults with CKD, both NDD and DD; in Japan for anemia of CKD patients on dialysis with a supplemental New Drug Application for anemia of CKD patients not only dialysis underway. The U.S. Food and Drug Administration (FDA) has a target action date of December 20, 2020 for the drug for anemia of CKD in both DD and NDD. In Europe, it is under review for both patient sets and was filed by their partner Astellas on May 21, 2020.
The MACE and MACE+ results, in particular, support the company’s regulatory filings. The company’s rival, Akebia, failed to hit that improvement with its own anemia associated with CKD drug, vadadustat, last week. The drug met its primary and key secondary efficacy endpoints in two studies but failed to meet the primary safety endpoint.
Of the FibroGen data, Yaron Werber, an analyst with Cowen, wrote in a note to clients, “Based on the data, we think roxadustat sets a high bar for both efficacy and safety as the potentially first-in-class HIF-PHI drug. We have high conviction that roxadustat will receive broad approval for both NDD- and DD-CKD by its 12/20/20 PDUFA.”
And Werber wasn’t the only analyst impressed by the results.
Geoffrey Porges, an analyst with SVB Leerink wrote, “This is important to roxa and its commercial outlook, since the increased CV risk associated with Higher Hb cost ESAs a blackbox in 2011 and reduced revenue by more than half. This post-hoc analysis won’t necessarily guarantee a blackbox-free label for roxa, but it demonstrated very encouraging signals that roxa is a safer oral formulation for the treatment of chronic kidney disease (CKD) anemia.”
