Amgen's Aranesp gains approval for anemia
When darbepoetin alfa (Aranesp, Amgen) won federal approval to treat anemia associated with chronic renal failure, that was only one of several news-making events about the drug. Amgen soon filed for federal approval of darbepoetin for the treatment of chemotherapy-related anemia.
Meanwhile, even during the initial publicity blitz about darbepoetin's approval for renal-related anemia, an Amgen official emphasized the importance of educating healthcare providers and consumers about the frequently ignored, widespread signs of anemia in the general population. Judging from Amgen's past campaigns promoting its recombinant human erythropoietin (EPO), such educational emphasis is almost a sure sign that Amgen intends to have darbepoetin approved to treat many kinds of anemia.
One fact may be driving this headlong push toward widespread use of darbepoetin (less often called "novel erythropoiesis-stimulating protein"). Though the drug is a unique molecule, it performs like EPO (Epogen, Amgen; Procrit, Ortho Biotech), except for the fact that darbepoetin's terminal half-life is three times longer than EPO's. So patients receive darbepoetin much less often, said researcher Ravi Thadhani, M.D., assistant professor of medicine, Harvard Medical School, Boston.
Even darbepoetin's side effects and adverse reactions are comparable to those associated with EPO, Thadhani said during a teleconference.
The list price of darbepoetin is $399 per mcg, but with less-frequent dosing the new drug's per-patient cost is comparable to EPO's, Amgen officials said. Also, less-frequent dosing will make the drug more popular among patients who must supply a copayment for each injection.
As similar as the two drugs are, there are some minor differences:
Amgen may promote EPO as the well-established drug of choice for hemodialysis patients since they can get in-line injections during their frequent visits for dialysis. Amgen may also promote darbepoetin mainly for the large number of anemic people needing less-frequent dosing, although once-weekly EPO works for some patients, said Wendy St. Peter, Pharm.D., associate professor of pharmacy, University of Minnesota, and a clinical R.Ph. at Hennepin County Medical Center, Minneapolis. She works with dialysis patients and United Renal Data Services.
A large market exists just among chronic renal patients who have not progressed to end-stage renal disease. No more than 28% of patients with chronic renal disease receive EPO for even a short time before starting dialysis, St. Peter told Drug Topics. Use of the drug could also be significant among cancer patients. Amgen said 50% to 60% of cancer patients who undergo chemotherapy experience anemia.
As with EPO, patients must realize the importance of taking iron supplements with darbepoetin. Oral supplements work well for most patients. However, recent research shows hemodialysis patients fare better taking IV supplements, said St. Peter.
One of pharmacists' most important tasks could be helping patients realize they might have anemia, St. Peter said, because many patients think the symptoms simply are an unavoidable part of aging or a disease.
With its potentially segmented marketing strategy, Amgen may not drop EPO's price. Ortho Biotech reported it doesn't plan to drop Procrit's price. In fact, that price went up 3.5% in September as part of an increase Ortho implemented for all of its products.
A head-to-head study comparing darbepoetin with EPO at the same dosing intervals will be the only way to determine whether darbepoetin will displace EPO, St. Peter said. Among the 12 clinical trials already done with darbepoetin, Amgen highlighted two in its media materials.
One of darbepoetin's approval studies analyzed 166 chronic renal insufficiency patients who had not previously received EPO. Darbepoetin given once weekly performed comparably to EPO given twice weekly. Subjects in the 24-week study had baseline hemoglobin values < 11.0 gm/dl and received either 0.45 mcg/kg of darbepoetin once weekly or 50 U/kg of EPO twice weekly. Dosage adjustments maintained hemoglobin within the study target range of 11.0 gm-13.0 gm/dl. (The recommended hemoglobin target is not to exceed 12 gm/dl, which is lower than the target range of this study.)
Among the 129 darbepoetin patients, 93 achieved the primary efficacy end point of an increase in hemoglobin of > 1.0 gm/dl from baseline to a value of > 11.0 gm/dl. The EPO and darbepoetin had the same seven-week median time to achieve the hemoglobin target.
In a 32-week study of 519 dialysis patients switching from EPO to darbepoetin, IV or subcutaneous darbepoetin, dosed once weekly, successfully maintained hemoglobin levels. All but 3% of patients switched from EPO, given two or three times weekly, to once-weekly darbepoetin. Among patients receiving EPO once weekly, 95% switched to darbepoetin given once every other week.
The federally approved starting dose of darbepoetin is 0.45 mcg/kg administered intravenously or subcutaneously once weekly. Darbepoetin should be given once every two weeks to patients who were receiving EPO once weekly. Additionally, some chronic renal insufficiency patients not taking EPO may be treated successfully with darbepoetin administered once every two weeks. For full prescribing information, see www.Aranesp.com .
Single-dose vials are available in five strengths, 25, 40, 60, 100, or 200 mcg. Multidose vials will appear eventually, Beckworth said. Two formulations use either polysorbate solution or albumin solution for excipients.
For information about treating chemotherapy-related anemia with darbepoetin, see studies in the April issue of the British Journal of Cancer, St. Peter said.
Steve Carrell. New anemia drug offers patients more convenience. Drug Topics 2001;21:28.