By Randall Osborne

West Coast Editor

Amgen Inc. is landing a one-two punch with disclosures of data from experiments with Aranesp (darbepoetin alfa) - a novel, second-generation, hyperglycosylated erythropoiesis stimulating protein (NESP) - for use against anemic conditions related to kidney disease and to cancer.

The drug, for which a new drug application has been filed, was the subject of a legal dispute with the company's development partner for EPO, Johnson and Johnson (J&J). That fight is finished "only in terms of arbitration," said David Kaye, spokesman for Thousand Oaks, Calif.-based Amgen. "Now, we'll be competing against each other."

At Sunday's 33rd annual meeting of the American Society of Nephrology (ASN), Amgen offered findings from a Phase II/III study in 166 patients with chronic renal insufficiency (CRI), in which kidney function is lower but does not yet require dialysis.

The study compared patients treated once weekly with Aranesp to patients treated twice weekly with recombinant Epoetin alfa (called rHuEPO in the study), resulting in similar safety profiles and comparable increases in hemoglobin levels in both groups.

"It's below normal levels, but it's a moderate level of hemoglobin," Kaye said. "Obviously, it's fewer painful needle sticks, and having to go to the doctor fewer times."

The findings are important because they are the first showing efficacy in CRI, or pre-dialysis disease, Kaye said. "This is the precursor to end-stage renal disease," he said. "It's a new market for Amgen. This is where J&J markets Procrit."

In an agreement in 1985 with Ortho Pharmaceuticals Corp., a division of New Brunswick, N.J.-based J&J, Amgen gave J&J rights to sell Epoetin alfa (Procrit/Eprex) for non-dialysis uses in the U.S. and for all indications worldwide except in China and Japan. Amgen retained rights to sell its brand of Epoetin alfa (Epogen) for use dialysis patients in the U.S.

In June 1997, J&J claimed that the earlier agreement ensured rights to Amgen's second-generation product, with its three-fold longer half-life than EPO. Amgen, however, won all rights. (See BioWorld Today, Dec. 22, 1998, p. 1.)

Another Phase II/III trial, involving 122 dialysis patients who had not yet been treated with rHuEPO, yielded similarly satisfactory hemoglobin levels, the ASN meeting heard. Aranesp was well tolerated when dosed once weekly, also, as compared to rHuEPO three times per week.

A third, pivotal, Phase III trial of 28 weeks in 507 dialysis patients randomized the subjects to receive Aranesp once per week or rHuEPO three times per week. Despite the reduced frequency of dosage, patients kept their target hemoglobin levels.

Yet another Phase I/II trial tested 703 patients with end-stage renal disease. Researchers found the patients could maintain their target hemoglobin levels when treated with Aranesp once per week, as compared to rHuEPO two or three times per week. The same result was gained by switching patients from rHuEPO once per week to Aranesp, once every other week.

Amgen's filing for marketing approval for Aranesp with the FDA and Europe broadly covers renal disease and includes data from patients with pre-dialysis CRI as well as patients with chronic renal failure requiring dialysis. The filing was based on data from the treatment of more than 2,100 patients. At the ASN meeting last year, Amgen presented data from a Phase III trial with NESP in dialysis patients. (See BioWorld Today, Nov. 9, 1999, p. 1.)

"It's hard to project" when Aranesp will be launched, Kaye said. "It should be sometime next year."

The second research punch involving the drug is expected to be delivered today at the 25th annual meeting of the European Society of Medical Oncology, in Hamburg, Germany.

Amgen said it will disclose the first efficacy data from studies with Aranesp at multiple dose levels in anemic cancer patients getting myelotoxic chemotherapy. The data show 85 percent of the patients' anemia was corrected at the highest dose level of Aranesp.

The multicenter, randomized, open-label study showed Aranesp was safe and well tolerated. Data were drawn from 130 patients in four dose groups, given Aranesp for a maximum of 12 weeks. They were compared to three patients who received rHuEPO three times per week. Doses of rHuEPO were doubled if these patients failed to respond.

"Aranesp was still better," Kaye said. Endpoints included not only anemia correction, but also response rate and blood transfusions required. Adverse events were consistent with bone marrow-suppressing chemotherapy, and patients ended up needing fewer transfusions with Aranesp.

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