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 | Home > Pipeline > Indications/Uses > Anemia |
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Anemia Anemia Erythropoiesis Current pharmacological anemia therapy Full erythropoiesis: HIF-mediated therapeutic approach to
treating anemia FibroGen has identified a series of potent, orally active compounds that stabilize HIF. Preclinical experiments demonstrate that FibroGen's HIF stabilization compounds can act selectively as erythropoietic compounds, increasing circulating levels of endogenous EPO and inducing the expression of other genes involved in iron processing and in heme synthesis. In animal models of anemia, treatment with certain HIF stabilizers leads to elevation of hematocrit (packed red blood cell volume), hemoglobin, and amelioration of anemia. FibroGen is currently developing two erythropoietic compounds based on the company's HIF stabilization technology: FG-2216 and FG-4592. More information about the development of FG-2216 and FG-4592 can be found in the Products in Development section of this Web site. Expanding the market for anemia therapy Patients with chronic kidney disease who have not yet reached end-stage renal disease (the most severe category requiring transplant or dialysis) represent a large but under-penetrated market for anemia therapy. While over 75% of new dialysis patients are anemic, less than 25% of chronic kidney disease patients with anemia are treated with recombinant EPO prior to dialysis. These patients are typically still under the care of primary physicians and are not making regular visits to the nephrologist or to dialysis centers where recombinant EPO is typically administered. Injections of recombinant EPO are therefore particularly inconvenient for predialysis patients. In addition, some 5-15% of end-stage renal disease patients are refractory to recombinant EPO therapy and require costly blood transfusions.
The predialysis market for anemia therapy is not only under-penetrated but also growing, largely due to the diabetes epidemic. People with diabetes are at high risk of developing kidney complications. The American Diabetes Association estimates that 20-30% of people with diabetes will develop diabetic nephropathy, a progressive loss of kidney function that is the leading cause of end-stage renal disease. In the U.S., the Center for Disease Control estimates (as of the end of calendar year 2002) that there are 13 million diagnosed diabetics, and another 5.2 million undiagnosed patients. The sum total of 18.2 million diabetics represents 6.3% of the total population. The number of new cases of diabetes continues to accelerate, increasing from 878,000 in 1997 to 1.3 million in 2002, an increase of 48% (or an 8% compound annual growth rate) over the most recently reported five-year period. Total U.S. diabetic patients are projected to exceed 30 million by 2030. A study published in Kidney International (September 2004) underscores the importance of treating anemia associated with diabetic nephropathy as the results demonstrated that even mild anemia (Hb < 13.8 g/dL) increases risk for progression of nephropathy to end-stage renal disease in type 2 diabetes: the average increase in adjusted relative risk reported in the article was 11% for each 1 g/dL decrease in hemoglobin concentration. In addition to anemia associated with chronic kidney disease, there is a large class of patients who suffer from anemia of chronic disease, including severely anemic patients in the settings of cancer (independent of chemotherapy), rheumatoid arthritis, inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, and iron processing deficiencies. In many of these patients, inflammatory responses associated with chronic disease suppress the body's ability to make EPO and/or hemoglobin. Anemia in such patients is treated through blood transfusions, which pose the risk of transmitting infectious pathogens (e.g., viruses).
FibroGen's HIF stabilization technology offers hope for a new approach to treating anemia of chronic disease. Preclinical studies of FG-2216 have shown that HIF-mediated mechanisms can counteract the suppressive effects of inflammatory molecules TNF-alpha and IL-1-beta. These observations suggest that HIF-mediated anemia therapy may be highly effective in inflammatory conditions where recombinant EPO therapy has not yet been approved. Because HIF mobilizes other critical aspects of erythropoiesis, such as factors essential to iron utilization and heme synthesis, FibroGen's HIF-mediated anemia therapy could also be beneficial in treating patients with iron processing deficiency. A small molecule therapy is also expected to have economic and ease-of-use advantages over recombinant EPO, which is a protein therapy that must be injected, making it expensive and inconvenient and limiting its use in a large percentage of patients with anemia. There is also concern about the potential for developing Pure Red Cell Aplasia (PRCA), a rare blood disease, associated with immune responses in kidney in a small number of patients who received recombinant EPO via subcutaneous dosing. These patients, most of whom received a version of recombinant EPO marketed in Europe, developed specific antibodies that neutralized not only recombinant EPO but also endogenous EPO, resulting in significantly reduced red blood cell production. In some, the condition can be improved using immunosuppressive therapy, but the majority of those with PRCA will require frequent blood transfusions for life.
Due to the limited penetration of recombinant EPO therapy in a small fraction of the entire anemia patient population and the limited erythropoietic profile of recombinant EPO therapy, there is a compelling need for a simpler, less expensive, and broader reaching method for the management of anemia. FibroGen believes that there is significant opportunity in advancing anemia therapy with a safe and effective oral medicine that addresses these needs. |
