1 December 2020 - - Japan's Ministry of Health, Labour and Welfare approved Evrenzo (roxadustat) for the treatment of anemia of chronic kidney disease in adult patients not on dialysis, Japan-based pharmaceutical company Astellas Pharma Inc. (TSX: 4503) and US-based FibroGen, Inc. (NASDAQ: FGEN) said.

This marks the second approval in Japan for roxadustat through the Astellas and FibroGen collaboration, after the therapy was approved and launched for use in adult patients with anemia of CKD on dialysis last year.

This approval is based on results obtained from three clinical studies in more than 500 Japanese patients with anemia of CKD not on dialysis.

The first, an open-label Phase 3 conversion study versus active comparator, darbepoetin alfa, met the primary efficacy endpoint of non-inferiority and continued to demonstrate maintenance of hemoglobin levels over time.

Roxadustat was generally well tolerated, and the safety profile was comparable with that of darbepoetin alfa.1 The other two studies (one Phase 3 and one Phase 2) support the safety and efficacy of roxadustat in erythropoiesis-stimulating agent -untreated patients.

The approval of the supplementary New Drug Application for roxadustat in Japan for the treatment of anemia of CKD in adult patients not on dialysis triggers a milestone payment of USD 15m by Astellas to FibroGen.

As a first-in-class orally administered inhibitor of hypoxia-inducible factor prolyl hydroxylase, roxadustat increases Hb levels through a mechanism of action that is different from that of traditional ESAs.

As a HIF-PH inhibitor, roxadustat activates the body's natural protective response to reduced oxygen levels in the blood.

This response involves the regulation of multiple, coordinated processes that lead to the correction of anemia.

CKD is characterized by a progressive loss of kidney function caused by damage to the kidneys resulting from conditions such as hypertension, diabetes or immune-regulated inflammatory conditions.

Worldwide, 1 in 10 people are living with CKD.6 In Japan specifically, the prevalence of CKD has increased significantly over time.

Although CKD can occur at any age, it becomes more common in aging populations and the prevalence is increasing.8 In addition, CKD is predicted to become the fifth most common cause of premature death by 2040 globally.

It is a critical worldwide healthcare issue that represents a large and growing unmet medical need.

Anemia is a common complication of CKD,10 resulting from the failing kidneys' ability to produce erythropoietin, reduced oxygen sensing, and increased hepcidin and iron deficiency resulting from chronic inflammation.

Anemia affects approximately one-third of Japanese patients with Stage 3–5 CKD.

It is associated with significant morbidity and mortality in dialysis and non-dialysis populations, increasing in both prevalence and severity as kidney disease worsens.

Anemia of CKD increases the risk of adverse cardiovascular events, worsens renal outcomes and can negatively impact patients' quality of life.

Roxadustat is a first-in-class orally administered inhibitor of HIF-PH, which increases hemoglobin levels through a mechanism of action that is different from that of traditional ESAs.

As a HIF-PH inhibitor, roxadustat activates a response that occurs naturally when the body responds to reduced oxygen levels in the blood.

Roxadustat promotes red blood cell production through increased endogenous production of erythropoietin; improved iron absorption, transport and mobilization; and downregulation of hepcidin, which helps to overcome the negative impact of inflammation on hemoglobin synthesis and red blood cell production.

Roxadustat is approved and launched for the treatment of anemia of CKD in Japan and China in adult patients on dialysis and not on dialysis.

A New Drug Application for the treatment of anemia of CKD in patients both DD and NDD is under review by the US Food and Drug Administration with a decision expected in December 2020.

The marketing authorisation application for roxadustat for the treatment of anemia of CKD in patients both DD and NDD was accepted by the European Medicines Agency for review.

Several other licensing applications for roxadustat have been submitted by Astellas and AstraZeneca to regulatory authorities across the globe, which are currently in review.

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East and South Africa.

FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the US, China and other markets in the Americas and in Australia/New Zealand as well as Southeast Asia.