Date: 2016-07-25
Type of information: Treatment of the first patient
phase: 3
Announcement: treatment of the first patient
Company: FibroGen (USA - CA) Astellas Pharma (Japan)
Product: roxadustat
Action
mechanism: enzyme inhibitor/hypoxia inducible factor (HIF) prolyl hydroxylase inhibitor. Roxadustat (FG-4592) is an orally administered small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase activity, in development for the treatment of anemia in patients with chronic kidney disease (CKD). HIF is a protein transcription factor that induces the natural physiological response to conditions of low oxygen, "turning on" erythropoiesis and other protective pathways.
Disease: anemia associated with chronic kidney disease (CKD)
Therapeutic area: Kidney diseases - Renal diseases
Country: Japan
Trial details:
Latest
news: * On July 25, 2016, Astellas Pharma and FibroGen announced the dosing of the first patient in Phase 3 trials in Japan of roxadustat for treatment of anemia in chronic kidney disease (CKD), which triggered a $10 million milestone payment from Astellas to FibroGen. The initiation of Phase 3 studies in Japan follows the positive results from two Phase 2 studies in Japan of roxadustat in CKD patients on dialysis and in CKD patients not on dialysis. In the Phase 2 studies in Japan of CKD patients receiving dialysis and not receiving dialysis, roxadustat was well tolerated and met the primary objective of demonstrating dose-related rates of hemoglobin (Hb) increase measured over the first six weeks of treatment, as well as anemia correction and Hb maintenance over the 24-week treatment period. The Phase 2 study in Japan of CKD patients not on dialysis was a multi-center, randomized, parallel-group, placebo-controlled, double-blind study over 24 weeks. The subjects, 107 CKD patients not yet receiving dialysis, were randomized to one of three roxadustat treatment arms (50 mg, 70 mg, 100 mg) or to a placebo arm, with roxadustat orally administered three times weekly (TIW) for the first six weeks of the study to evaluate dose response of efficacy and safety. This was followed by dose titration every four weeks until hemoglobin response was achieved, at which point hemoglobin was maintained with patients randomized to one of two dosing regimens (continuation of TIW dosing or a change to weekly (QW) dosing). Results showed achievement in the full analysis set of dose response in the three roxadustat treatment arms, with a mean rate of Hb increase of 0.200, 0.453, and 0.570 g/dL per week (50 mg, 70 mg, 100 mg, respectively), as measured over the first six weeks of the study, compared to a mean Hb decrease of 0.052 g/dL per week in subjects receiving placebo. Of note, 93.8% of roxadustat-treated subjects achieved hemoglobin correction as measured by hemoglobin response defined as Hb more than or equal to 10 g/dL and Hb increase of at least 1 g/dL from baseline. In the placebo arm, hemoglobin response was achieved in 14.8% of the subjects. Roxadustat was well tolerated, with no deaths and no major adverse cardiovascular events reported for roxadustat-treated patients. The Phase 2 study in Japan in 130 CKD patients receiving dialysis was a multi-center, randomized, darbepoetin-controlled, double blind (roxadustat arms), open-label (darbepoetin) study over 24 weeks in CKD patients on chronic stable dialysis. The subjects who had discontinued previous standard-of-care therapy (erythropoiesis-stimulating agents) to reach Hb levels of < 9.5 g/dL were randomized to one of three roxadustat arms (administered orally TIW at a fixed dose) or to the darbepoetin arm (darbepoetin administered intravenously QW) over the first six weeks of the study to evaluate dose response of efficacy and safety, followed by dose titration to the desired Hb level every four weeks. During weeks 18 to 24, average Hb levels achieved (a secondary endpoint) in the full analysis set were 10.31 g/dL (1.33 g/dL Hb increase), 10.20 g/dL (1.37 g/dL Hb increase), and 10.53 g/dL (1.57 g/dL Hb increase), respectively, in the roxadustat treatment arms, compared to 10.25 g/dL (1.42 g/dL Hb increase) in the darbepoetin arm. Roxadustat was well tolerated in this study, with one death reported in a subject who suffered from bacterial pneumonia and thromboembolism, whose death was deemed unrelated to roxadustat; no deaths were reported in the other treatment arms. FibroGen and development partner Astellas have, in total, completed six roxadustat Phase 2 studies in CKD patients on dialysis and CKD patients not on dialysis in the U.S., Europe and China. The results reported in these Phase 2 studies in Japan are consistent with the results from the Phase 2 studies in other regions. Completion of these studies enabled Astellas to initiate the Phase 3 clinical development program in Japan in 2016. This is consistent with the ongoing Phase 3 clinical development program for roxadustat and treatment of anemia in CKD patients that includes 10 current Phase 3 studies: eight global studies in support of U.S. and Europe requirements and two studies in support of China marketing approval. * On June 9, 2016, FibroGen announced that it will receive a $10.0 million milestone payment from Astellas Pharma. This payment, whichFibroGen expects to receive by July 2016, was triggered by the initiation by Astellas of the first Phase 3 clinical study in Japan of roxadustat (ASP1517 or FG-4592) for treatment of anemia associated with chronic kidney disease (CKD) in patients on dialysis. Under the exclusive license and collaboration agreement with Astellas, Astellas is responsible for the development costs of roxadustat in Japan, and makes payments to FibroGen for certain development, regulatory, and commercial-based milestones.
