Amgen Inc. reported positive Phase III results at the American Society of Nephrology meeting in San Diego related to cinacalcet HCl when administered once daily for secondary hyperparathyroidism associated with chronic kidney disease.
More specifically, a greater proportion of patients in the cinacalcet HCl group (36 percent to 48 percent), compared to those receiving standard therapy (4 percent to 7 percent), achieved the primary endpoint of parathyroid hormone less than or equal to 250 pg/mL. Across the Phase III program, clinically relevant reductions in calcium-phosphorus product (13 percent to 17 percent), calcium (6 percent to 8 percent) and phosphorus (7 percent to 10 percent) occurred in patients receiving the first-in-class oral calcimimetic, while those receiving standard therapy and placebo remained at baseline levels.
The FDA has granted a priority review for the product, for which Thousand Oaks, Calif.-based Amgen filed a new drug application two months ago. Such designation positions the product for potential approval in early March. (See BioWorld Today, Sept. 10, 2003.)
"Priced at $1,000 per annum (approximately twice that of calcitriol), cinacalcet revenues in 2005 could be on the order of $235 million," William Tanner, an analyst with Leerink Swann & Co. in Boston, wrote in a research note. "More conservative patient populations, and that pricing assumption, imply a revenue opportunity of approximately $177 million."
Separately, Amgen reported other clinical results suggesting that Aranesp (darbepoetin alfa) may be administered once monthly in patients with anemia and chronic kidney disease. A 98-patient trial showed that 85 percent maintained hemoglobin levels within the target range while receiving Aranesp once monthly, with a mean hemoglobin of 11.1 g/dL following treatment with monthly administration.
In other news from the meeting:
• Advanced Magnetics Inc., of Cambridge, Mass., reported new clinical data on ferumoxytol, showing that the investigational intravenous iron replacement therapeutic is suitable in treating iron deficiency in hemodialysis patients receiving erythropoietin and can be delivered in larger doses and more rapidly than currently approved IV iron therapy products. Ferumoxytol has completed Phase II studies in that indication. It remains in Phase II for use as a contrast agent in magnetic resonance angiography, and is expected to enter Phase III trials next year.
• BioStratum Inc., of Research Triangle Park, N.C., said animal data showed that its lead drug candidate, Pyridorin, inhibited the progression of nephropathy as shown by the urinary albumin-to-creatinine ratio when combined with enalapril. In contrast, the ratio significantly increased in both the placebo group and the enalapril monotherapy group. Other data demonstrated that Pyridorin's mechanism of action is different from that of previously studied AGE inhibitors. Separate findings from an animal model of kidney stone formation showed that after induction of hyperoxaluria, urinary oxalate excretion in the Pyridorin-treated group decreased by about 50 percent, compared to untreated controls.
• Encysive Pharmaceuticals Inc., of Houston, and GlaxoSmithKline plc, of London, said an open-label, three-way crossover investigation showed that Argatroban was well tolerated and hemodialysis sessions were successfully completed in end-stage renal disease patients on maintenance hemodialysis. No serious adverse events or bleeding events occurred during the 13-patient trial, which was led by the University of Chicago hospitals. The product, a direct thrombin inhibitor, is indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia.
• Hoffmann-La Roche Inc., of Nutley, N.J., said initial Phase II results showed that dialysis patients with chronic renal anemia treated with CERA (Continuous Erythropoiesis Receptor Activator) received sustained stimulation of red blood cell formation at dosing intervals of up to once every three weeks. The results showed increased hemoglobin at all studied doses, with increasing doses providing a rapid response and extended dosing intervals not influencing the response.
• La Jolla Pharmaceutical Co., of San Diego, reported analyses showing statistically significant associations between changes from baseline in levels of antibodies to double-stranded DNA (dsDNA) and the relative risk of renal flare in both late-stage trials of Riquent. Analyses of data using Cox's Proportional Hazards Regression Model predict that a 50 percent reduction in antibodies to dsDNA from baseline is associated with a 52 percent lower risk of renal flare in the Phase II/III study (p=0.0007) and a 53 percent lower risk in the Phase III trial (p<0.0001). The results will be submitted as part of the company's planned regulatory filing, which it expects to submit around the end of the year. (See BioWorld Today, May 6, 2003.)
• Nabi Biopharmaceuticals, of Boca Raton, Fla., said data from a recently completed clinical trial show that its PhosLo (calcium acetate) product is significantly more efficacious than Renagel (sevelamer hydrochloride, Genzyme Corp.) in controlling serum-phosphorous and calcium-phosphorous product in end-stage renal disease patients on hemodialysis. The eight-week, randomized, double-blinded, controlled study called CARE (Calcium Acetate Renagel Evaluation) compared the efficacy of calcium acetate and sevelamer.
• The Rikshospitalet University Hospital in Oslo, Norway, reported results of separate analyses from the ALERT (Assessment of Lescol in Renal Transplantation) study demonstrate that lipid levels are key risk factors for myocardial infarction and cardiac death in renal transplant recipients. In addition, early introduction of Lescol (fluvastatin, Reliant Pharmaceuticals LLC) shortly after transplantation significantly reduced the risk of coronary heart disease.