FibroGen (FGEN) Highlights Results from Ph. 3 HIMALAYAS Trial Evaluating Roxadustat for Treatment of Anemia in Incident Dialysis Patients

FibroGen, Inc. (NASDAQ: FGEN), today announced results from the Phase 3 HIMALAYAS trial evaluating roxadustat for the treatment of anemia in incident dialysis (ID) patients with chronic kidney disease (CKD), a clinically important subgroup of dialysis-dependent CKD patients. Incident dialysis was defined as those who initiated dialysis within 4 months before randomization to roxadustat or epoetin alfa. In this trial of 1,043 patients, believed to be the largest trial to date investigating an anemia medicine in the ID population, roxadustat achieved both primary efficacy endpoints. The safety profile of roxadustat observed in the HIMALAYAS trial was consistent with results observed in previous roxadustat studies.

This incident dialysis subpopulation is appropriate for comparison of roxadustat versus epoetin alfa, as patients experience high rates of morbidity and mortality during the period of initial dialysis treatment, whereas the stable dialysis population consists of patients who have survived this period and are already shown to be responsive to stable ESA doses.

“Roxadustat is the first of a new class of medication, applying the groundbreaking science on oxygen sensing and adaptation to hypoxia recently awarded the 2019 Nobel Prize in Physiology or Medicine,” said Robert Provenzano, MD, Associate Professor of Medicine, Wayne State University, Detroit, Michigan, U.S. and lead investigator of the HIMALAYAS study. “The positive HIMALAYAS results highlight the potential of roxadustat as an attractive new treatment option for anemia in these highly vulnerable patients who are new to dialysis care. This study provides useful insights and clinically relevant data for consideration in clinical practice, as most patients start anemia treatment when they begin dialysis.”

HIMALAYAS is an open label, active controlled, global Phase 3 study in which 1,043 incident dialysis patients were randomized 1:1 to receive roxadustat or epoetin alfa for up to 4.4 years, with mean treatment duration of 1.8 years. The U.S. primary efficacy endpoint of mean change in hemoglobin (Hb) levels from baseline to the average over 28-52 weeks was met as roxadustat was shown to be non-inferior to epoetin alfa, followed by demonstration of superiority (p=0.0005). The mean Hb increased from 8.4 g/dL to 11.0 g/dL in roxadustat-treated patients vs. 8.4 g/dL to 10.8 g/dL in epoetin alfa-treated patients. Roxadustat was non-inferior to epoetin alfa in the EU primary efficacy endpoint of proportion of patients achieving a Hb response (defined as Hb ≥11.0 g/dL and Hb increased by ≥1 g/dL from baseline) during the first 24 weeks of treatment: 88.2% in the roxadustat arm vs. 84.4% in the epoetin alfa arm. Further, patients treated with roxadustat required lower average monthly intravenous iron use than those treated with epoetin alfa (p=0.00028).

The most frequently observed adverse events (AEs) with roxadustat in the HIMALAYAS trial were hypertension, diarrhea, and muscle spasms.

“We are encouraged by these HIMALAYAS efficacy and safety results which suggest roxadustat to be a promising treatment for anemia in incident dialysis CKD patients who have newly initiated dialysis therapy,” said K. Peony Yu, MD, Chief Medical Officer, FibroGen. “These results create the opportunity to potentially improve anemia care in dialysis patients initiating treatment by offering a novel and effective oral therapy.”

These data (TH-OR201) were featured in the oral abstract session, Anemia and Iron Metabolism: Clinical Research, at the American Society of Nephrology (ASN) Kidney Week 2019 in Washington, D.C.

In the same oral abstract session as HIMALAYAS, FibroGen’s collaboration partner AstraZeneca will present study results from the Phase 3 OLYMPUS and ROCKIES trials, assessing roxadustat as a treatment for anemia in non-dialysis and dialysis-dependent patients with CKD, respectively.

Data from the HIMALAYAS trial is included in pooled efficacy and cardiovascular safety analyses of the roxadustat Phase 3 clinical development program, which will be presented during the ASN Kidney Week High-Impact Clinical Trials oral abstract session on Friday, November 8 at 2:00 PM EST.

About Anemia Associated with CKD Anemia can be a serious medical condition in which patients have insufficient red blood cells and low levels of hemoglobin, a protein in red blood cells that carries oxygen to cells throughout the body. Anemia in CKD is associated with increased risk of hospitalization, cardiovascular complications and death, also frequently causing significant fatigue, cognitive dysfunction and reduced quality of life. Severe anemia is common in patients with CKD, cancer, myelodysplastic syndromes (MDS), inflammatory diseases, and other serious illnesses.

Anemia is particularly prevalent in patients with CKD. The prevalence of CKD in the adult population is estimated at 10-12% globally, and is generally a progressive disease characterized by gradual loss of kidney function that may eventually lead to kidney failure, or end stage renal disease, requiring dialysis or kidney transplant to survive. Blood transfusion is used for treating life-threatening severe anemia. However, blood transfusions reduce the patient’s opportunity for kidney transplant, increase risk of infections and the risk of complications such as heart failure and allergic reactions.

According to the United States Renal Data System (USRDS), over 14% of the U.S. adult population is affected by CKD, and a majority of dialysis-eligible CKD patients are currently on dialysis. It is estimated that approximately 509,000 patients are receiving dialysis in the U.S. as of 2016.

About Roxadustat Roxadustat (FG-4592) is a first-in-class, orally administered small molecule HIF-PH inhibitor that promotes erythropoiesis through increasing endogenous production of erythropoietin, improving iron regulation, and overcoming the negative impact of inflammation on hemoglobin syntheses and red blood cell production by downregulating hepcidin. Administration of roxadustat has been shown to induce coordinated erythropoiesis, increasing red blood cell count while maintaining plasma erythropoietin levels within or near normal physiologic range in multiple subpopulations of chronic kidney disease (CKD) patients, including in the presence of inflammation and without a need for supplemental intravenous iron. Roxadustat is currently approved in China for the treatment of anemia in CKD patients on dialysis and patients not on dialysis and approved in Japan for the treatment of anemia in CKD patients on dialysis. Roxadustat is in Phase 3 clinical development in the U.S. and Europe and in Phase 2/3 development in China for anemia associated with myelodysplastic syndromes (MDS), and in a Phase 2 U.S. trial for treatment of chemotherapy-induced anemia.

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in territories including Japan, Europe, the Commonwealth of Independent States, the Middle East, and South Africa. AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in the U.S., China, and other markets in the Americas and in Australia/New Zealand as well as Southeast Asia.

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