Newswise — A new risk predictor for diagnosing kidney disease and measuring its progression could help physicians focus treatment efforts more efficiently, says study findings co-authored by University of Alabama at Birminghamresearchers and published in the May 9, 2012 issue of the Journal of the American Medical Association.

More than 26 million Americans have chronic kidney disease, according to the National Kidney Foundation, and the more accurately it can be diagnosed, the better physicians can prevent its progression to kidney failure and other related complications including heart disease and death.

Using the newest risk predictor, the Chronic Kidney Disease Epidemiology Collaboration equation, or CKD-EPI, fewer individuals in the study were classified as having chronic kidney disease. This equation more accurately categorized the risk for death and end-stage renal disease than its more widely used counterpart, the Modification of Diet in Renal Disease Study equation. The findings suggest that switching to the CKD-EPI equation could help physicians focus treatment efforts more efficiently and improve assessment of a patient’s risk of end-stage renal disease and other complications.

Kidney function is measured by estimating glomerular filtration rate using kidney filtration markers that are present in the blood. A higher filtration rate means healthy kidney function. A lower rate indicates kidney disease and is used to measure its progression.

“Compared to the MDRD Study equation, the CKD-EPI equation more accurately estimates GFR using the same variables — age, sex, race and serum creatinine level — especially at higher GFR,” says UAB co-author David Warnock, M.D., Hilda B. Anderson Endowed Chair in Nephrology in the UAB Division of Nephrology. “It also more consistently classified future complication risks — mortality and the need for dialysis — than the MDRD Study equation. This was true across a wide range of populations.”

The study, which included data from more than 1 million adults ages 18 years and older in 40 countries or regions — Asia, Europe, North America, South America, Middle East and Oceania — compared the risk for adverse outcomes using estimated GFR calculated by the CKD-EPI versus GFR calculated by the MDRD Study equation. The primary adverse outcomes the researchers looked at were all-cause mortality, cardiovascular mortality and end-stage renal disease.

“About one-third of patients with mild to moderate kidney disease had a higher GFR category when the CKD-EPI equation was used compared to the MDRD Study equation,” Warnock says. “The same group also had up to a two-fold lower risk of dying or developing end-stage renal disease — even after adjusting for other factors that affect kidney disease risk.”

Currently, more than 90 percent of the medical laboratories in the United States use the MDRD Study equation more than 300 million times each year to assess kidney function.

“I believe this study is conclusive evidence that the CKD-EPI equation translates to better risk prediction and should become the standard,” Warnock says. “It allows more accurate GFR estimation, lower CKD prevalence estimates and better risk categorization by the CKD-EPI equation without additional costs.”

The study’s lead author is Kunihiro Matsushita, M.D, Ph.D., of Johns Hopkins Bloomberg School of Public Health. Other authors are Bakhtawar K. Mahmoodi, M.D., Ph.D., and Josef Coresh, M.D., Ph.D., Johns Hopkins Bloomberg School of Public Health; Mark Woodward, Ph.D., Johns Hopkins Bloomberg School of Public Health and George Institute, University of Sydney, Australia; Jonathan R. Emberson, Ph.D., Oxford University, Oxford, United Kingdom; Tazeen H. Jafar, M.D., M.P.H., Aga Khan University, Karachi, Pakistan; Sun Ha Jee, Ph.D., M.H.S., Yonsei University, Seoul, Korea; Kevan R. Polkinghorne, FRACP, MClinEpi, Ph.D., Monash University, Victoria, Australia; Anoop Shankar, M.D., M.P.H., Ph.D., West Virginia University School of Medicine, Morgantown, W.Va.; David H. Smith, R.Ph., Ph.D., Kaiser Permanente Northwest, Portland, Ore.; Marcello Tonelli, M.D., S.M., Departments of Medicine, University of Alberta, Edmonton, Alberta, Canada; Chi-Pang Wen, M.D., Dr.P.H., of China Medical University Hospital, Zhunan, Taiwan; Bakhtawar K. Mahmoodi, M.D., Ph.D., and Ron T. Gansevoort, M.D., Ph.D., University Medical Center Groningen, Groningen, the Netherlands;
Brenda R. Hemmelgarn, M.D., Ph.D., University of Calgary, Calgary, Alberta, Canada; and Andrew S. Levey, M.D., Tufts Medical Center.

The study was performed for the research group, the Chronic Kidney Disease Prognosis Consortium. It was established by Kidney Disease: Improving Global Outcomes, a global non-profit foundation dedicated to improving the care and outcomes of kidney disease patients worldwide. Funding for the research was provided by the National Kidney Foundation.

Screening for, Monitoring, and Treatment of Chronic Kidney Disease Stages 1 to 3

A Systematic Review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline

From article published  in Annals of Internal Medicine on April 17, 2012

and online at  U.S. Preventive Services Task Force

By Howard A. Fink, MD, MPH; Areef Ishani, MD, MS; Brent C. Taylor, PhD, MPH; Nancy L. Greer, PhD; Roderick MacDonald, MS; Dominic Rossini, MD; Sameea Sadiq, MD; Srilakshmi Lankireddy, MD; Robert L. Kane, MD; and Timothy J. Wilt, MD, MPH.

Abstract

Background: Screening and monitoring for chronic kidney disease (CKD) could lead to earlier interventions that improve clinical outcomes.

Purpose: To summarize evidence about the benefits and harms of screening for and monitoring and treatment of CKD stages 1 to 3 in adults.

Data Sources: MEDLINE (1985 through November 2011), reference lists, and expert suggestions.

Study Selection: English-language, randomized, controlled trials that evaluated screening for or monitoring or treatment of CKD and that reported clinical outcomes.

Data Extraction: Two reviewers assessed study characteristics and rated quality and strength of evidence.

Data Synthesis: No trials evaluated screening or monitoring, and 110 evaluated treatments. Angiotensin-converting enzyme inhibitors (relative risk, 0.65 [95% CI, 0.49 to 0.88]) and angiotensin II–receptor blockers (relative risk, 0.77 [CI, 0.66 to 0.90]) reduced end-stage renal disease versus placebo, primarily in patients with diabetes who have macroalbuminuria. Angiotensin-converting enzyme inhibitors reduced mortality versus placebo (relative risk, 0.79 [CI, 0.66 to 0.96]) in patients with microalbuminuria and cardiovascular disease or high-risk diabetes. Statins and β-blockers reduced mortality and cardiovascular events versus placebo or control in patients with impaired estimated glomerular filtration rate and either hyperlipidemia or congestive heart failure, respectively. Risks for mortality, end-stage renal disease, or other clinical outcomes did not significantly differ between strict and usual blood pressure control. The strength of evidence was rated high for angiotensin II–receptor blockers and statins, moderate for angiotensin-converting enzyme inhibitors and β-blockers, and low for strict blood pressure control.

Limitations: Evidence about outcomes was sometimes scant and derived from post hoc analyses of subgroups of patients enrolled in trials. Few trials reported or systematically collected information about adverse events. Selective reporting and publication bias were possible.

Conclusion: The role of CKD screening or monitoring in improving clinical outcomes is uncertain. Evidence for CKD treatment benefit is strongest for angiotensin-converting enzyme inhibitors and angiotensin II–receptor blockers, and in patients with albuminuria combined with diabetes or cardiovascular disease.

Primary Funding Source: Agency for Healthcare Research and Quality

Highlights

• A policy instituted in 2005 has reduced racial disparities in deceased-donor kidney transplantation among children.
• Since the institution of the policy, called Share 35, fewer children receive kidneys from living donors.
• More than 800 children and adolescents in the U.S. are waiting for a kidney transplant.

Washington, DC (April 26, 2012) — A policy instituted in 2005 has reduced racial disparities in kidney transplantation among children, according to a study appearing in an upcoming issue of theJournal of the American Society Nephrology (JASN). Children are better off receiving kidneys from live donors, though, and receiving organs from deceased donors can diminish the limited supply of organs available to kidney failure patients on waiting lists.

Everyone with kidney failure deserves a transplanted kidney that works well. But because children with the disease have the greatest long-term potential for a healthy future, in 2005 the United Network for Organ Sharing instituted a policy, Share 35, to preferentially offer kidneys from younger (< 35 years of age) deceased donors, who are more likely to have been healthier at the time of their deaths than older donors, to pediatric patients. (The United Network for Organ Sharing manages the nation’s organ transplant system under contract with the federal government.)

What effects have Share 35 had on kidney transplantation? For example, in the past, black and Hispanic children with kidney failure experienced reduced access to transplantation compared with white children. Has Share 35 had an impact on these racial disparities? Also, has Share 35 inadvertently promoted deceased organ donation over living donation for children in need of a kidney transplant?

To answer these and other questions, Sandra Amaral, MD (The Children’s Hospital of Philadelphia) and her colleagues analyzed data from the US Renal Data System before and after Share 35. These data applied to 2,299 pediatric kidney failure patients who received a transplant before Share 35 and 2,467 patients who received one after.

Among the major findings:

• On average, patients were 46% more likely to receive a deceased-donor kidney transplant after Share 35 was implemented, with increases of 81% for Hispanics, 45% for blacks, and 37% for whites.
• Patients received a deceased-donor kidney transplant earlier after Share 35: 201 days earlier for Hispanics, 90 days earlier for blacks, and 63 days earlier for whites.
• All races experienced a shift from living- to deceased-donor sources after Share 35, with a 48% reduction in living donors for Hispanics, a 46% reduction for blacks, and a 25% reduction for whites.

These results indicate that Share 35 has attenuated racial disparities in terms of how likely and how soon children will receive a deceased-donor kidney transplant.

“Reduced racial disparities in access to deceased donor kidney transplant for children with end-stage kidney disease is a very positive step toward achieving equity in overall transplant access for all children; however, greater declines in living donors for all pediatric patients, particularly for those of black or Hispanic ethnicity, may be a concern,” said Dr. Amaral. “Less access to living donors for children with end-stage kidney disease may mean that these patients have less access to the best quality kidneys and less potential for the best graft survival,” she explained. More studies are needed to understand how these changes will impact racial differences in the long-term health of transplanted kidneys.

Study co-authors include Rachel Patzer, PhD, Nancy Kutner, PhD, and William McClellan, MD (Emory University).

Home-based dialysis is more popular in developing countries, less so in developed

LONDON, ON –Researchers at Lawson Health Research Institute have discovered that developing countries have faster growing rates of use of home-based dialysis (called peritoneal dialysis) for kidney failure than the developed world. Despite home-based dialysis’ reduced cost and better outcomes, developed countries (including Canada) are using this form of therapy less.

The study by Dr. Arsh Jain, Lawson researcher and Nephrologist at London Health Sciences Centre, was published in the Journal of American Society Nephrology (JASN) last month. Peritoneal dialysis represents only 11 per cent of dialysis patients worldwide.

While the overall use of peritoneal dialysis for kidney failure is climbing world wide, rates are climbing quickly in developing countries. According to Dr. Jain, peritoneal dialysis is more cost effective than hospital-based dialysis (called hemodialysis). Dr. Jain and his colleagues analyzed records from 1997 to 2008 in 130 countries in order to come up with the conclusion that developed countries are using peritoneal dialysis less.

The study found that 59 per cent of peritoneal patients were treated in developing countries as opposed to 41 per cent in developed countries. Throughout the 12 years of the study, peritoneal dialysis patients in developing countries increased by 24.9 patients per million populations and in developed countries only 21.8 per million populations. Despite this increase the overall proportion of all dialysis patients that are treated with peritoneal dialysis in developed countries has in fact declined by 5.3 per cent, while developing countries have had no change.

“Our findings may impact future business and research innovations,” said Dr. Jain. “It may be the developing world and not the developed world that drives future medical innovations in peritoneal dialysis.” These results also serve as a call to action for developed countries to increase the use of this effective therapy.

PALO ALTO, Calif. & OSAKA, Japan, Apr 24, 2012 (BUSINESS WIRE) — Affymax, Inc. and Takeda Pharmaceutical Company Limited , today announced that OMONTYS(R) (peginesatide) Injection is now available only for use in treating anemia due to chronic kidney disease (CKD) in adult patients on dialysis. OMONTYS is the only once-monthly erythropoiesis-stimulating agent (ESA) for anemia available to the dialysis patient population in the United States. OMONTYS is co-marketed by Affymax and Takeda Pharmaceuticals U.S.A. (TPUSA) and distributed by TPUSA.

See below for Full Indication, Limitations of Use and Important Safety Information including Boxed WARNINGS.

OMONTYS was approved by the U.S. Food and Drug Administration (FDA) on March 27, 2012. It is administered either intravenously (IV) or subcutaneously (SC) as a single monthly injection. Dialysis providers interested in ordering OMONTYS should contact their group purchasing organizations (GPOs), specialty distributors or call 1-855-GOMONTYS (1-855-466-6689).

“Today’s announcement represents an important milestone in the field as nephrologists and anemia nurses will now be able to use the first once-monthly treatment for anemia for adult dialysis patients available in the United States,” said John Orwin, chief executive officer, Affymax. “We are excited to partner with the dialysis community and support the important work they do for patients.”

“We look forward to working with the dialysis community as they implement this once-monthly medicine into their practice,” said Douglas Cole, president, Takeda Pharmaceuticals U.S.A. “In partnership with Affymax, we will support the providers and physicians as they convert their adult CKD patients on dialysis to OMONTYS.”

Takeda’s consolidated financial statements for the 2011 fiscal year will be announced on May 11, 2012. The fiscal 2012 outlook and Mid-Range Plan 2012-14 will also be presented, which will include this product launch.

About OMONTYS

OMONTYS(R) (peginesatide) Injection is a synthetic, pegylated, peptide-based ESA. It is the only ESA that is peptide-based and its building blocks (amino acids) are arranged in a different order than erythropoietin (i.e., it has no sequence homology to endogenous erythropoietin).

On March 27, 2012, the United States Food and Drug Administration approved OMONTYS for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis. OMONTYS is not indicated and is not recommended for use in patients with CKD not on dialysis, in patients receiving treatment for cancer and whose anemia is not due to CKD, or as a substitute for red blood cell (RBC) transfusions in patients who require immediate correction of anemia. OMONTYS has not been shown to improve symptoms, physical functioning or health-related quality of life.

OMONTYS is the only once-monthly erythropoiesis-stimulating agent (ESA) for anemia available to the dialysis patient population in the United States.

In February 2012, Takeda and its wholly-owned subsidiary, Takeda Global Research & Development Centre (Europe) Ltd. announced the acceptance of a Marketing Authorization Application (MAA) for peginesatide by the European Medicines Agency (EMA). The application is currently under review by that agency.

About Anemia Due to CKD in Adult Patients on Dialysis

Anemia (a condition in which blood has a lower than normal number of red blood cells) is a common complication in CKD patients on dialysis because their kidneys no longer produce enough erythropoietin, the hormone that stimulates red blood cell production in the body. As of 2009, the United States Renal Data System noted there were nearly 400,000 people in the United States who were on dialysis. According to the Centers for Medicaid and Medicare Services (CMS), nearly 95 percent of dialysis patients in the United States are being treated for anemia with ESAs.

For more information about OMONTYS, visit www.omontys.com .

IMPORTANT SAFETY INFORMATION

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE.

Chronic Kidney Disease:

* In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.

* No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.

* Use the lowest OMONTYS dose sufficient to reduce the need for red blood cell (RBC) transfusions.

Contraindications

OMONTYS is contraindicated in patients with uncontrolled hypertension.

Warnings and Precautions

Increased mortality, myocardial infarction, stroke, and thromboembolism:

– Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiovascular disease and stroke. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of >1 g/dL over 2 weeks may contribute to these risks

– In controlled clinical trials of ESAs in patients with cancer, increased risk for death and serious adverse cardiovascular reactions was observed. These adverse reactions included myocardial infarction and stroke

– In controlled clinical trials of ESAs, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and deep venous thrombosis (DVT) in patients undergoing orthopedic procedures

– In 2 trials of OMONTYS, patients with CKD not on dialysis experienced increased specific cardiovascular events

Increased mortality and/or increased risk of tumor progression or recurrence in patients with cancer: The safety and efficacy of OMONTYS have not been established for use in patients with anemia due to cancer chemotherapy. OMONTYS is not indicated in patients with cancer receiving chemotherapy.

Hypertension: OMONTYS is contraindicated in patients with uncontrolled hypertension. Appropriately control hypertension prior to initiation of and during treatment with OMONTYS. Reduce or withhold OMONTYS if blood pressure becomes difficult to control. Advise patients of the importance of compliance with antihypertensive therapy and dietary restrictions.

Lack or loss of response to OMONTYS: For lack or loss of hemoglobin response to OMONTYS, initiate a search for causative factors. If typical causes of lack or loss of hemoglobin response are excluded, evaluate for antibodies to peginesatide.

Dialysis management: Patients receiving OMONTYS may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.

Laboratory monitoring: Evaluate transferrin saturation and serum ferritin prior to and during OMONTYS treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%.

Adverse reactions

The most common adverse reactions in clinical studies in patients with CKD on dialysis treated with OMONTYS were dyspnea, diarrhea, nausea, cough, and arteriovenous fistula site complication.

Please click here for Full Prescribing Information including Boxed WARNINGS, or visit www.omontys.com .

About Affymax, Inc.

Affymax, Inc. is a biopharmaceutical company based in Palo Alto, California. Affymax’s mission is to discover, develop and deliver innovative therapies that improve the lives of patients with kidney disease and other serious and often life-threatening illnesses.

The company’s first marketed product, OMONTYS, was approved by the U.S. Food and Drug Administration (FDA) in March 2012. For additional information on Affymax, please visit www.affymax.com .

This release contains forward-looking statements, including statements regarding the potential advantages of OMONTYS, the continuation and success of Affymax’s collaboration with Takeda, the timing and potential for EMA review of the MAA and the commercialization of OMONTYS. Affymax’s actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties, including risks relating to EMA review of the MAA, regulatory requirements by the FDA, the EMA or other regulatory authorities, including post-marketing studies and Risk Evaluation and Mitigation Strategy, the continued safety and efficacy of OMONTYS, the timing of patient accrual in ongoing and planned clinical studies, industry and competitive environment, financing requirements and our ability to access capital and other matters that are described in Affymax’s Annual Report on Form 10-K filed with the Securities and Exchange Commission. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Affymax undertakes no obligation to update any forward-looking statement in this press release.

About Takeda Pharmaceutical Company Limited

Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com .

About Takeda Pharmaceuticals U.S.A., Inc. and Takeda Global Research & Development Center, Inc.

Based in Deerfield, Ill., Takeda Pharmaceuticals U.S.A., Inc. and Takeda Global Research & Development Center, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology, gastroenterology and cardiovascular disease treatments and seek to bring innovative products to patients through a pipeline that includes compounds in development for diabetes, gastroenterology, neurology and other conditions. To learn more about these Takeda companies, visit www.tpna.com .

This press release contains forward-looking statements. Forward-looking statements include statements regarding Takeda’s plans, outlook, strategies, results for the future, and other statements that are not descriptions of historical facts. Forward-looking statements may be identified by the use of forward-looking words such as “may,” “believe,” “will,” “expect,” “project,” “estimate,” “should,” “anticipate,” “plan,” “assume,” “continue,” “seek,” “pro forma,” “potential,” “target,” “forecast,” “guidance,” “outlook” or “intend” or other similar words or expressions of the negative thereof. Forward-looking statements are based on estimates and assumptions made by management that are believed to be reasonable, though they are inherently uncertain and difficult to predict. Investors are cautioned not to unduly rely on such forward-looking statements.

Forward-looking statements involve risks and uncertainties that could cause actual results or experience to differ materially from that expressed or implied by the forward-looking statements. Some of these risks and uncertainties include, but are not limited to, (1) the economic circumstances surrounding Takeda’s business, including general economic conditions in Japan, the United States and worldwide; (2) competitive pressures and developments; (3) applicable laws and regulations; (4) the success or failure of product development programs; (5) actions of regulatory authorities and the timing thereof; (6) changes in exchange rates; (7) claims or concerns regarding the safety or efficacy of marketed products or product candidates in development; and (8) integration activities with acquired companies.

The forward-looking statements contained in this press release speak only as of the date of this press release, and Takeda undertakes no obligation to revise or update any forward-looking statements to reflect new information, future events or circumstances after the date of the forward-looking statement. If Takeda does update or correct one or more of these statements, investors and others should not conclude that Takeda will make additional updates or corrections.

SOURCE: Affymax, Inc. April 25 2012