Date: 2016-07-08
Type of information: Milestone
Compound: roxadustat (FG-4592)
Company: AstraZeneca (UK) Fibrogen (USA - CA)
Therapeutic area: Kidney diseases - Renal diseases
Type agreement: development
commercialisation
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) and end-stage renal disease (ESRD)
Details: * On July 31, 2013, AstraZeneca and FibroGen have announced that they have entered into a strategic collaboration to develop and commercialize FG-4592, a first-in-class oral compound in late stage development for the treatment of anemia associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD).
The AstraZeneca-FibroGen joint effort will be focused on the development of FG-4592 to treat anemia in CKD and ESRD, and may be extended to other anemia indications. In Phase II clinical studies, FG 4592 met its primary objective of demonstrating anemia correction in treatment-naïve CKD patients not on dialysis as well as maintenance of hemoglobin levels and anemia correction in patients on dialysis. FG 4592 has demonstrated this efficacy combined with an acceptable safety profile in clinical trials, and has been shown to achieve anemia correction in the absence of intravenous iron supplementation. The companies plan to undertake an extensive FG-4592 Phase III development program for the US, and to initiate Phase III trials in China, with anticipated regulatory filings in China in 2015 and in the US in 2017.
AstraZeneca will be responsible for the US commercialization of FG-4592, with FibroGen undertaking specified promotional activities in the ESRD segment in this market. The companies will also co-commercialize FG-4592 in China where FibroGen will be responsible for clinical trials, regulatory matters, manufacturing and medical affairs, and AstraZeneca will oversee promotional activities and commercial distribution.
This collaboration focuses on the US, China and all major markets excluding Japan, Europe, the Commonwealth of Independent States, the Middle East and South Africa, which are covered by an existing agreement between FibroGen and Astellas Pharma. The Japan rights were licensed to Yamanouchi (now Astellas) in 2004. In 2006, FibroGen has then completed an exclusive licensing agreement with Astellas Pharma that provides Astellas development and marketing rights to certain FibroGen HIF prolyl hydroxylase inhibitors for the treatment of anemia in Europe, Commonwealth of Independent States (CIS), Middle East, and South Africa. These inhibitors include FG-2216 and FG-4592. The two partners have just announced the initiation of a Phase 2 clinical study in Japan of ASP1517/FG-4592 for treatment of anemia associated with chronic kidney disease (CKD) in patients on dialysis. Astellas also plans to conduct an additional Phase 2 clinical study in Japan in non-dialysis patients in late 2013. In December 2012, Astellas and FibroGen announced the initiation of the first clinical study in the Phase 3 development of ASP1517/FG-4592 to support approval in the U.S. and Europe.
Financial terms: AstraZeneca will pay FibroGen committed upfront and subsequent non-contingent payments totaling $350 million, as well as potential future development related milestone payments of up to $465 million, and potential future sales related milestone payments in addition to tiered royalty payments on future sales on FG-4592 in the low 20 percent range. Additional development milestones will be payable for any subsequent indications which the companies choose to pursue.
Latest news: * On July 8, 2016, FibroGen announced that it has received a scheduled $62 million license payment pursuant to its collaboration agreement with AstraZeneca for the United States and certain other territories. AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat (FG-4592) for the treatment of anemia in patients with CKD in the U.S., China, and other markets. Roxadustat is currently in Phase 3 development as a potential therapy for anemia associated with chronic kidney disease in both patients on dialysis and not on dialysis. * On June 29, 2015, FibroGen announced that it has received a scheduled $120.0 million non-contingent license payment from AstraZeneca under its collaboration agreements with AstraZeneca for roxadustat in the United States, China and certain other territories. In addition to this non-contingent license payment of $120.0 million, as previously announced, FibroGen received a $15.0 million milestone payment from AstraZeneca during the second quarter of 2015 in connection with the completion of long-term preclinical safety studies of roxadustat. On a pro-forma basis, FibroGen expects to have approximately $410 million to $415 million of cash, cash equivalents, investments, and receivables on June 30, 2015 (unaudited). Roxadustat is currently in Phase 3 global development for the treatment of anemia in patients with chronic kidney disease (CKD) on dialysis and not on dialysis. The global development program is being conducted by FibroGen and its partners, AstraZeneca and Astellas Pharma Inc. Approximately 8,000 CKD patients will be enrolled in 10 clinical trials. Regulatory filings are expected to be submitted in 2016 for China and in 2018 for the US. * On May 7, 2015, FibroGen announced that it has received a $15 million milestone payment from AstraZeneca, triggered by the completion of roxadustat non-clinical carcinogenicity studies. In two separate two-year carcinogenicity studies, in rats and in mice, there was no evidence of a roxadustat-related effect on mortality or carcinogenicity.
