Ferumoxytol Treatment for Kidney Disease

The National Kidney Foundation estimates 20 million Americans (one in nine adults) suffer from kidney disease. Kidney disease can lead to diabetes, high blood pressure, other disorders and kidney failure. 15 In the United States, ninth leading cause of death is kidney disease. 6

Two kidneys in the human body filter blood and remove waste products and extra water which becomes urine, carried away through the bladder. The bladder stores the urine until it is excreted through the urethra. Twenty percent of the blood gets filtered under pressure in the kidneys. 1 The nephrons in the kidney are tiny structures which filter the blood. 2 The kidneys have millions of nephrons enough in reserve in case a number of nephrons become damaged which is irreversible. However, when at least half of the total number of nephrons is damaged, kidney disease is inevitable, and resulting in renal failure. Nephrons may be damaged by Injury (trauma), Infection, drugs harmful to the kidneys, decreased blood flow, stones lodged in the urethra or ureters disrupt urine outflow, and toxins including antifreeze. 3 Common causes for kidney failure diabetes, high blood pressure and hereditary factors. After filtering the blood, healthy kidneys regulate chemicals in the body: Sodium, phosphorus, and potassium are released in the body. "The right balance is necessary for life, but excess levels can be harmful." Symptoms of kidney diseases urinate less or more frequently, fatigue, loss of appetite, nausea, vomiting, feet or hands swell or feel numb, trouble concentrating or feeling drowsy, skin appears dark and muscle cramps. Laboratory results confirm kidney disease besides other tests: Creatinine (Waste product in the blood normally excreted through the urine) increases in the blood. During the latest stage of kidney disease, require dialysis (filter and clean the blood) or kidney transplant. 4 In 2005, Renal Data System ('USRDS is a national data system that collects, analyze, and distributes information about end -stage renal disease in the United States". 7) estimated 340,000 patients undergoing dialysis treatment. 6

"Anemia is common in people with kidney disease." When healthy blood cells (carry sufficient amount of oxygen to the vital organs of the body) are low contribute to heart problems. Disease kidneys unable produce a hormone erythropoietin (EPO) stimulates the bone narrow to establish a proper number of red blood cells to carry oxygen. 5 Iron deficiency indicates presence of anemia. When hematocrit (hct -measure percentage of red blood cells) and hemoglobin (measure iron in the blood) blood tests are low suggests anemia as a diagnosis. 8

In May 2008, AMAG (Advanced Mangetic's) Pharmaceuticals (biopharmaceutical company - develops iron therapy treatments for cardiovascular disease and cancer 12) reported during the Eighth American Transplant Congress in Toronto, Canada positive Phase three Studies of Ferumoxytol as an intravenous iron replacement for treating anemia in kidney disease patients. During trial study 31 chronic kidney disease patients received two doses 510 mg of intravenous ferumoxytol or 200 mg of oral iron daily replacement. After thirty five days, statistically positive results were shown. 9 Bruce S. Spinowitz, M.D. clinical professor of medicine, Weill Medical College of Cornell University said: "Ferumoxytol improved hemoglobin and iron stores in study subjects more effectively than oral iron and was well tolerated." 10 Effectiveness of ferumoxytol may not require patients to receive dosages of red blood cell stimulating drugs or reduce their dosage. 14 In August 2008, study results published in the Journal of the American Society of Nephrology. 10 Total of 1,700 clinical patients treated during various phases studies, supported positive ferumoxytol results. However, 1.1% of ferumoxytol subjects compared to 2.8% among oral iron replacement treatment incidence of deaths followed. In December 2007, AMAG Pharmaceuticals filed New Drug Application with Food and Drug Administration (FDA), seeking marketing approval for ferumoxytol for treatment of iron deficiency in patients with chronic kidney disease. 6 Expected by October 19, 2008 FDA will grant approval of ferumoxytol and by the first quarter of 2009 AMAG Pharmaceuticals begin sale of the iron drug. 10 Also, AMAG pharmaceuticals is in the process of hiring sales representatives. 11

Various Wall Street brokerage firm analysts have opposite opinions regarding FDA approval of ferumoxytol. Jefferies & Company analyst Adam Walsh and Robert W. Baird analyst Christopher J. Raymond expect FDA approval and raised target price of AMAG Pharmaceuticals public traded stock to $99.00 and $80 respectively. Also, Robert W. Baird said: "Ferumoxytol is easier to administer than currently approved intravenous supplements". However, Merrill Lynch Andrew Berens estimates 20% chance the FDA will grant approval and may require the pharmaceutical company additional clinical information regarding ferumoxytol. 11 During the Jefferies & Company Health Care Conference (June 27, 2007) in New York at 12:30 pm ET, Brian J. G. Pereira MD, President and CEO of Advanced Mangetics, will provide an overview of the company. 16

In China 12 million people diagnosed with stage 3 and 4 kidney disease and 91,000 people on dialysis. AMAG Pharmaceuticals signed agreement with 3SBio Incorporated (Chinese Biotechnology Company) develop and market ferumoxytol to treat iron deficiency anemia in China, provided the drug gets regulatory approval. AMAG pharmaceuticals will receive $1 million and subsequent royalties up to twenty-five percent from sales of ferumoxytol. 12 "The agreement has an initial duration of 13 years but will be automatically renewed if minimum sales thresholds are met". 13

References:

1.) How Your Kidneys Work - http://health.howstuffworks.com/kidney.htm

2.) Kidney Diseases - http://www.nlm.nih.gov/medlineplus/kidneydiseases.html

3.) Renal (Kidney) Failure - http://www.gcvs.com/internists/renal.htm

4.) Your Kidneys and How They Work - http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/index.htm

5.) Anemia in Kidney Disease and Dialysis - http://kidney.niddk.nih.gov/kudiseases/pubs/anemia/

6.) AMAG Pharmaceuticals Provides Clinical Information On Ferumoxytol As An Intravenous Iron Replacement Therapeutic in Chronic Kidney Disease Patients - http://www.medicalnewstoday.com/articles/95884.php

7.) USRDS - http://www.usrds.org/

8.) Anemia management and chronic kidney disease - http://www.davita.com/dialysis/complications/a/1798

9.) AmAG Pharmaceuticals, Inc. Announces Presentation of Positive Results from Phase III Studies of Ferumoxytol as an Intravenous Iron Replacement Thearpy in Kidney Transplant Recipients at the American Transplant Congress - http://biz.yahoo.com/bw/080531/20080531005022.html?.v=1

10.) AMAG's iron drug fermuoxytol has positive results in phase 3 study - http://www.renalbusiness.com/hotnews/amag-ferumoxytol-positive-results.html

11.) AMAG shares down, but analysts upbeat on lead drug - http://biz.yahoo.com/ap/080609/amag_mover.html?.v=2

12.) 3SBio pays AMAG Pharma $1M to sell ferumoxytol in China - http://www.masshightech.com/stories/2008/05/26/daily5-3SBio-pays-AMAG-Pharma-$1M-to-sell-ferumoxytol-in-China.html

13.) AMAG Pharmaceuticals in development and commercialization pact with 3SBIO -http://www.iii.co.uk/news/?type=afxnews&articleid=6730538&subject=companies&action=article

14.) New iron drug improves anemia with kidney disease - http://www.sciam.com/article.cfm?id=new-iron-drug-improves-an

15.) Advanced Magnetics up on positive trial - http://www.spectroscopynow.com/coi/cda/detail.cda?id=15068&type=News&chId=3

16.) Advanced Magnetics, Inc, Provide Update on Timing of Final Ferumoxytol Phase III Results - http://www.redorbit.com/news/health/982523/advanced_magnetics_inc_provides_update_on_timing_of_final_ferumoxytol/index.html?source=r_health