Anemia Markets
Anemia Affects Millions but is Currently Undertreated
Chronic kidney disease (CKD) is a crisis in the US healthcare system. In 2005, CKD accounted for 27% of Medicare expenses ($60 billion). Between the National Health and Nutrition Evaluation Surveys (NHANES) 3 and 4, prevalence of CKD increased from 10% to 13% of the US adult population or approximately 20 million US adults in 1988-94 vs. 29 million in 1999-2004.
Approximately 5.6 million CKD patients are in the later stage of disease (Stages 3b-5, eGFR <45) and it is estimated that 1.1 million of these later stage nondialysis patients are anemic with hemoglobin levels below 11 g/dL. Prevalence of anemia increases as CKD progresses. In addition to these 1.1 million nondialysis patients with anemia, nearly all hemodialysis patients (350,000) become anemic due to hemodialysis treatments.
Current Therapies Pose Significant Challenges in Access to Care
Although Erythropoiesis Stimulating Agents (ESAs) were introduced nearly two decades ago, the CKD anemia market is still limited to treatment of approximately 95% of the 350,000 US dialysis patients. It is estimated that only 150,000 nondialysis patients receive ESA treatment. There is limited access to anemia therapy until a patient is referred to a nephrologist, which is usually only immediately prior to the initiation of dialysis, although multiple studies and medical organizations have pointed to the importance of early-in-CKD treatment of anemia in improving CKD outcomes.
One important driver of this pattern of undertreatment is that CKD patients are referred very late from their primary care physicians to nephrologists who have access to ESAs. In fact, only 56% of incident dialysis patients have been under the care of a nephrologist prior to initiating dialysis. While dialysis patients are in the care of specialty nephrologists, the nondialysis patients are in the care of endocrinologists, internal medicine specialists and primary care physicians who do not have ready access to ESAs.
Undertreatment of anemia in nondialysis represents a significant unmet medical need and commercial opportunity for FibroGen. Further, within the dialysis population, ESA hyporesponders stand out as an important market opportunity.
Recent Changes in Markets for ESA Therapies
US anemia markets have contracted over the past two years as a result of FDA actions. Most of the impact has been in the oncology setting. Off-label use in cancer-related anemia outside of chemotherapy has been discredited and reminders have been added to prescribing information that use in cancer is not indicated unless patients are receiving concomitant myelosuppressive chemotherapy. In addition, significant concern with thrombotic and embolic events in cancer populations has led to significant limitations in usage.
Most recently, on July 30, 2008, FDA, following the guidance of the Oncologic Drugs Advisory Committee (ODAC), FDA directed Amgen and Johnson & Johnson to further modify the labeling for ESAs in the chemotherapy-induced anemia (CIA) indication. The revised labeling directs prescribers that “ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.” Further, FDA reiterated that “therapy should not be initiated at hemoglobin levels = 10 g/dL.” Previous guidance allowed that patients with comorbid conditions could be considered for higher hemoglobin targets.
In contrast, the CKD related anemia market has not significantly declined. FDA has reinstituted a target hemoglobin range of 10-12 g/dL in response to criticism that previous label direction to give the lowest dose of ESA to avoid transfusion did not give prescribers enough guidance and overlooked the clear benefits of maintaining hemoglobin from 11-12 g/dL. The Centers for Medicare Services (CMS), which has had a major impact in oncology to limit treatment initiation to below hemoglobin 10 g/dL did not try to impose such a limit in CKD. CKD differs from the oncology setting due to the rigorous clinical studies performed and debated over many years showing clear net benefit to patients for correction to hemoglobin 11-12 g/dL.
Between Amgen (Epogen® and increasingly Aranesp®) in dialysis and Johnson and Johnson (subcutaneous Procrit®) and Amgen (Aranesp®) in nondialysis, the CKD-ESRD category produces about $3.5 billion of US ESA sales today. We believe that there will continue to be significant growth in this category for several reasons:
- Underlying Population Growth: The CKD population is growing at a rate in excess of the base population growth and aging rates (NHANES shows a CAGR of >6% from the mid-1990’s). CKD is now estimated to affect approximately 30 million people, due to drivers such as increasing obesity, diabetes and hypertension rates.
- New Anemia Market Entrants Trying to Address Nondialysis Market: New competitors poised to enter the US anemia market including Roche’s CERA, Affymax’s Hematide and AMAG Pharmaceutical’s Ferumoxytol are all aiming at the nondialysis population, but cannot address the basic issues in primary care – ease of use (all are injected products), routine reimbursement and affordability.
- Increasing Evidence on Benefit of Anemia Treatment in Nondialysis: Recent studies suggest that anemia care in nondialysis is far more than palliative. Gouva (2004) showed that anemia treatment in CKD slowed renal disease progression compared with no anemia treatment,1 raising the possibility that low dose EPO is renoprotective.2 In addition, according to a pharmacoeconomic study of employees with nondialysis CKD, anemia treatment was associated with increased hemoglobin levels, improved productivity, and decreased direct employer costs, ultimately saving approximately $4400 per patient per year.3 In addition, major policy organizations are lining up in favor of early therapy in CKD. One example is the UK National Institute of Clinical Excellence (NICE). NICE stated in their 2006 monograph on anemia treatment that “the patients most likely to derive the greatest long-term benefit from correction of anemia are those with chronic kidney disease who are nondialysis. Early intervention to correct anemia has the potential to impact on the progression of chronic kidney disease and affect patient morbidity, hospitalization rates, quality of life and mortality.”
References
1. Gouva C, et al. (2004) Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int 66:(2):753-760.
2. Singh AK (2007) Does correction of anemia slow the progression of chronic kidney disease? Nat Clin Pract Nephrol 3: (12):638-639.
3. Papatheofanis F, et al. (2008) An examination of productivity and resource utilization associated with epoetin alfa treatment in employees with predialysis chronic kidney disease. J Occup Environ Med 50(5):584-9.
