FibroGen, Inc., announced that its investigational oral anaemia therapy, FG-4592, received Clinical Trial Application (CTA) approval from the Chinese State Food and Drug Administration (SFDA) to commence clinical development for the treatment of anaemia associated with chronic kidney disease (CKD) in the People's Republic of China.
FG-4592 is a first-in-class hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI) entering phase 2b clinical development in the US and Europe for the treatment of CKD anaemia. SFDA approved protocols for both phase 1 and 2 studies. The first of these studies of FG-4592 in China will begin in the fourth quarter of 2010.
“This is a significant milestone in the global expansion of our development programme for FG-4592,” said Thomas B. Neff, CEO of FibroGen. “With the support of SFDA, we are committed to bringing safe, effective and accessible oral anaemia therapy to the people of China.”
In October 2009, SFDA accepted FG-4592 for Special Examination and Approval of the Registration of New Drugs, otherwise known as ‘Green Channel.' This designation by the SFDA has allowed FibroGen to establish close communication with the Center for Drug Evaluation (CDE) in the determination of clinical development plans in China. “As we continue a productive dialog with the CDE, we will explore options to bring FG-4592 to the expanding Chinese market as rapidly as possible, including possible submission of FG-4592 as a domestic first-in-class NDA,” said Neff.
Phase 1 and 2 trials in China are expected to have completed dosing by the end of 2011. In parallel with completion of these studies, phase 3 plans and commercialization strategy, including identification of potential partners, will be determined.
CKD is a chronic progressive disease that ultimately leads to end-stage renal disease (ESRD) necessitating kidney transplant or dialysis. Global prevalence rates of CKD are far higher in industrial countries than in rural settings. As the Chinese economy has grown, a large portion of the population has moved to urban settings where accompanying changes in diet and exercise have led to increased prevalence of CKD risk factors including diabetes and hypertension. As a result, studies have shown that CKD prevalence in China has reached levels similar to that of the US, resulting in approximately 125 million Chinese people with CKD.
The prevalence of anaemia increases as CKD worsens, resulting in fatigue, loss of exercise capacity, diminution of cognitive abilities and reduced independence. The unmet medical need for treatment of anaemia in China is large. Nearly all of the approximately 300,000 Chinese CKD patients who reach the end-stage every year are anaemic and approximately 6-8 million Chinese CKD patients not yet on dialysis are anaemic.
At present, it is estimated that only 10% of anaemic patients are treated. This is largely because providing anaemia care has been difficult in the past. Erythropoiesis Stimulating Agents (ESA), injectable supplements of recombinant human erythropoetin or analogs, were first made available in China in the early 1990’s at high Western prices. In addition, at that time there was a limited health insurance system in China, so provision of care for ESRD patients, including dialysis and anaemia treatment, was greatly limited.
In recent years, China’s government has initiated a dramatic revolution in reimbursement that has increased health care affordability, particularly for complex, expensive disease states such as ESRD requiring dialysis treatment. The number of Chinese with health insurance has increased ten-fold in the past decade to an estimated 1.2 billion, nearly all of the 1.3 billion people in China, in 2010. Further, the level of insurance coverage has been expanded to the point where complex medical procedures such as dialysis have become affordable for many.
The scope and scale of insurance reform continues to increase. In particular, the Chinese government has made treatment of CKD a national health care priority. Focused government efforts have resulted in the rapid expansion of dialysis services, including creation of additional haemodialysis facilities in urban areas and increased use of peritoneal dialysis in the countryside, and improved access to ESA therapy.
The current ESA market in China is relatively small but growing with increased patient access to dialysis. Although the anaemic patient population is four times that of the US, only one sixth the number of US anaemia patients is currently treated. In addition to previous limitations on health insurance and access to dialysis services, high cost of ESA, complexity of administration as well as need for refrigerated transport and storage have contributed to low ESA sales. As a result, the ESA market in China was only $100 million vs. $5 billion in the US in 2009.
In addition, except in certain major hospitals, anaemic CKD patients generally go untreated, resulting in low average haemoglobin levels. The only publicly available data on haemoglobin levels in China is from the Shanghai Dialysis Registry where patients on average are corrected to 10.3 g/dL. Since Shanghai is among the Chinese cities with the highest level of medical treatment in the country, the haemoglobin correction level reached across China is believed to be lower than that in Shanghai, less than 10 g/dL, compared with an average of 11.8 g/dL among dialysis patients in the US.
Given the vast geography, the size of population and the aggregate healthcare cost of dialysis treatment in the country, the need for oral anaemia therapy is far greater in China than in Western countries. FG-4592 could potentially revolutionize anemia treatment in China by offering less expensive, more easily administered oral therapy, particularly for the 70% of people residing in rural areas far from tertiary hospitals and predialysis patients who are still employed and are challenged to come to medical centers frequently to receive ESA injections. Th greater treatment accessibility offered by FG-4592 will potenitally enable more patients to be treated to the higher haemoglobin targets that are recommended by medical associations worldwide, allowing for better patient outcomes.
FG-4592 is a novel, orally-active investigational compound that works through an entirely different mechanism of action than that of ESA. FG-4592 activates HIF, the key regulatory protein that coordinates all elements of erythropoiesis necessary for proper formation of mature red blood cells plump with iron-rich, oxygen-carrying hemoglobin molecules. HIF also down-regulates hepcidin, a regulatory hormone that limits iron availability and thus suppresses erythropoiesis under conditions of inflammation. Preclinical and early clinical data suggest that FG-4592 may offer several safety and efficacy advantages over current ESA therapy including correction of anaemia with more physiologic levels of erythropoietin, not increasing blood pressure and providing efficacious treatment of patients who are hyporesponsive to ESA.
Certain rights to FG-4592 are licensed to Astellas Pharma Inc. for Japan, Europe, Commonwealth of Independent States (CIS), Middle East, and South Africa. FibroGen retains full rights in North and South America, remaining parts of Africa and all of Asia Pacific ex-Japan.
FibroGen, Inc. is a biotechnology-based drug discovery and development company using its expertise in the fields of tissue fibrosis, connective tissue growth factor (CTGF), and hypoxia-inducible factor (HIF) biology to discover, develop, and commercialize novel therapeutics for fibrotic disorders, diabetic complications, anaemia, conditions associated with tissue damage or injury, cancer, and other areas of unmet medical need.