Several recent clinical studies suggest that ARANESP™, a novel erythropoiesis stimulating protein (NESP) not yet approved by the Food and Drug Administration, allows for less frequent dosing of anemic patients than recombinant epoetin alfa (r-HuEPO, also known as EPO). Although the majority of the studies addressed the treatment of patients with chronic renal insufficiency (CRI) and chronic kidney disease requiring dialysis, biotechnology developer Amgen is also pursuing the use of ARANESP™ to treat anemia in oncology patients. The potential benefits of less frequent dosing on patient management, compliance, and administrative burden are being evaluated in current and planned clinical trials.

In the most significant of the nephrology studies, a phase II/III trial tested 122 patients on dialysis who had not received prior r-HuEPO therapy. Daniel W. Coyne, M.D., associate professor of medicine, Washington University School of Medicine, reported that ARANESP™ achieved target hemoglobin levels when administered at a starting dose of 0.45 µg/kg once weekly, and was comparable to r-HuEPO administered three times weekly.

"Potentially, NESP could replace EPO for dialysis patients," said Dr. Coyne. "The safety profile has been comparable. Less frequent administration of the drug means higher compliance. For most patients, especially those requiring sub-q shots, like peritoneal and pre-dialysis patients, the fewer shots, the better."

In a 24-week phase 2/3 study, 166 patients with CRI who did not require dialysis treatment were randomized to receive either NESP administered once weekly at a starting dose of 0. 45µg/kg or EPO administered twice weekly. Francesco Locatelli, M.D., Azienda Ospedialiera di Lecco, Lecco, Italy, and colleagues reported that the two groups exhibited similar safety profiles and comparable increases in hemoglobin levels.

In a third trial, a pivotal double-blinded 28-week phase 3 study, 507 patients undergoing dialysis were randomized either to switch from EPO three times a week to NESP once a week, or to remain on EPO three times a week. According to Allen R. Nissenson, M.D., F.A.C.P., professor of medicine and the director of the dialysis program, UCLA, NESP enabled dialysis patients to maintain target hemoglobin levels (the mean change in Hgb concentration from baseline to week 36 was 0.16 g/dL). Both treatment groups exhibited similar safety profiles. "When EPO was approved by the FDA in 1989, it was one of the most important breakthroughs in the treatment of dialysis patients," said Dr. Nissenson. "The possibility that EPO could be improved, with the development of NESP, was an exciting one. It was for this reason and the potential value of NESP to patients that I decided to participate in the study." He also noted the benefits that the dosing trials suggest: "In addition to in-center hemodialysis patients, NESP should have particular advantages in home dialysis and CKD patients not yet on dialysis."

Chronic kidney disease is characterized by decreased levels of erythropoietin, a hormone that helps stimulate the production of red blood cells. Reduced hormone levels result in lowered production of red blood cells, or anemia. When left untreated, anemia can significantly impair a patient's quality of life and also may cause serious problems such as cardiac enlargement and ischemia.

Amgen presented the NESP trials data for treating CRI and dialysis patients to the 33rd annual meeting of the American Society of Nephrology in Toronto on October 15, 2000. The following day the company presented additional findings to the European Society of Medical Oncology concerning the use of NESP to treat anemic cancer patients. Preliminary studies suggest that patients receiving NESP require fewer blood transfusions than currently utilized therapy, according to John Glaspy, M.D., professor of medicine, UCLA. The oncology studies are less extensive than the nephrology studies, and additional trials will be required before more definitive conclusions about NESP's broader applications can be drawn.

Ortho Biotech, the maker of Procrit (r-HuEPO), has not yet compared the efficacy of the two drugs. "Because there's limited published data on ARANESP, we can't make any statements about the safety or efficacy of ARANESP," said Ortho Biotech product manager Carol Goodrich. "However, our position is that in both of these markets--oncology and nephrology--there's room for a tremendous amount of growth."