AstraZeneca's recent collaboration with Fibrogen to develop and commercialize FG-4592 (ASP1517), a small molecule HIF-PIF inhibitor in Phase III development for anemia in chronic kidney disease (CKD), is an unusual move by the company. Historically, neither hematology nor anemia have been areas of interest for AstraZeneca, and the deal is another example of the company's recent surge of business development activity aimed at replenishing its diminishing late stage pipeline. The collaboration spans the United States, China and other markets, but excludes Japan, Europe, the Middle East and South Africa, which are covered by an existing agreement between Fibrogen and Astellas which took place in 2006. In our opinion, this deal is a good move by AstraZeneca as it offers a near-term commercial opportunity in a lucrative market.
FG-4592 (ASP1517): a novel MOA in treating anemia in CKD
FG-4592 (ASP1517) is an oral inhibitor of hypoxia inducible factor-prolyl hydroxylase (HIF-PIH). HIF-PIH inhibitors create hypoxic conditions, which increases the natural production of erythropoetin (EPO) thus causing an increase in hemoglobin in anemia patients. HIF also down-regulates hepcidin, a regulatory hormone that limits iron availability and suppresses erythropoeisis when inflammation is occurring. The drug is in Phase III development for anemia in patients with CKD who are not on dialysis and those on dialysis.
FG-4592 represents a novel mechanism of action in a disease stage that is largely treated by erythropoietin stimulating agents (ESAs) and IV iron replacement products. The ESAs control erythropoiesis (red blood cell production) thus increasing hemoglobin levels. A previously booming drug class with notable blockbusters such as Amgen's Epogen (epoetin alfa), this class has been hit by a string of negative factors, namely safety concerns. Top-line results from the Phase III TREAT trial released in 2008 showed that Aranesp (darpepoetin alfa) increased the risk of stroke events. Following the announcement of these results in 2011, the FDA lowered the dose of ESAs required to treat anemia in CKD. Aside from safety concerns, changes to reimbursement guidelines and biosimilar competition in Europe are all contributing to the class' declining sales.
An expensive but potentially worthwhile deal
AstraZeneca will pay a hefty upfront fee of $350m, with future milestone payments of up to $465m. Additional development milestones are payable for any subsequent indications which the companies decide to explore. In the United States, AstraZeneca will be responsible for the commercialization of FG-4592, while Fibrogen undertakes certain promotional activities within the end-stage renal disease (ESRD) segment of this market. For a deal centered on the United States and China (excluding most other ROW markets), the potential total amount ($815m) is pricey but adds an innovative Phase III candidate in a large and growing indication. The estimated prevalence of CKD in the United States is about 7 percent of the population, which represents about 22 million people (National Health and Nutrition Examination Survey, NHANES).
We also note that the drug is a fine strategic fit with the company's core therapy area of cardiovasculars. CKD patients carry a high burden of cardiovascular disease and dyslipidemia. Early stage results of FG-4592 in anemia in CKD have demonstrated the drug's ability to reduce cholesterol and blood pressure; features which we expect to be a bonus in the clinical management of anemia patients. We believe the company will use its experience in the cardiovascular space to explore further and communicate the cardiovascular benefits of FG-4592 compared to other therapies. Clinical development in other closely related indications such as chemotherapy-induced anemia and, anemia caused as a result of MDS are also possible.
FG-4592 enters a competitive market dominated by ESA brands such as Amgen's Epogen (U.S.) and J&J's Procrit/Eprex (ROW). Roche's Mircera (PEG - epoetin alfa) has a long-acting profile and, superior regimen compared to the older generation ESAs and is expected to launch in the United States in 2014; it will also pose a threat. However, given that FG-4592 is a non-biologic, we expect it to be cheaper compared to the ESAs, which should aid reimbursement especially in markets like China where the infrastructure is less well established. Additionally, the drug's oral route of delivery and cardiovascular benefits noted in trials (lowers cholesterol and blood pressure) should aid uptake. We would expect FG-4592 to enhance AstraZeneca's footing in the U.S. market. The company has a strong position in China and has stated its intention to continue to build on its strength in this region and re-focus around innovative products in emerging markets. Thus, FG-4592 should help the company to meet these goals.
Efua Edusei is an analyst on the Pharmaview team at Decision Resources.