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|Amgen Announces EVOLVE Trial(TM) To Investigate Impact of Sensipar(R)/Mimpara(R) (cinacalcet HCl) on Mortality and Cardiovascular Morbidity in Secondary Hyperparathyroidism Patients With Chronic Kidney Disease Receiving Dialysis|
GLASGOW, Scotland--(BUSINESS WIRE)--July 16, 2006-- -- New Data Showed Earlier Intervention With Sensipar/Mimpara Improved Ability to Achieve K/DOQI(TM) Secondary HPT Treatment Guidelines in Dialysis Patients --
Amgen (Nasdaq:AMGN), the world's largest biotechnology company, announced today the initiation of the largest prospective, randomized clinical trial planned to date in patients with stage five chronic kidney disease (CKD). EVOLVE (EValuation Of Cinacalcet Therapy to Lower CardioVascular Events)(TM) is a Phase 3 international, clinical outcomes study designed to determine whether Sensipar(R)/Mimpara(R) (cinacalcet HCl) can effectively reduce the risk of mortality and cardiovascular morbidity in patients with secondary hyperparathyroidism (secondary HPT) and CKD undergoing maintenance dialysis. EVOLVE was announced at the 2006 European Renal Association - European Dialysis and Transplant Association (ERA-EDTA). Cinacalcet HCl is marketed as Sensipar in the United States, Canada and Australia and as Mimpara in the European Union.
Amgen's decision to initiate EVOLVE is supported by a recent post-hoc analysis of four pooled, prospective, randomized, placebo-controlled clinical trials that showed treatment with cinacalcet HCl in patients with secondary HPT and CKD receiving dialysis resulted in improvement of clinical outcomes, including cardiovascular hospitalization, parathyroidectomy, fracture and health-related quality of life.(1)
"Recent data have shown a relationship between poorly controlled secondary HPT and increased mortality and morbidity in CKD patients receiving dialysis," said Willard Dere, MD, senior vice president for global development and chief medical officer at Amgen. "Until EVOLVE, no robust prospective, clinical trial has definitively determined whether treating secondary HPT reduces the risk of cardiovascular events. The results of the EVOLVE will be invaluable to nephrologists in deciding how to optimally manage secondary HPT."
EVOLVE is expected to enroll approximately 3,800 patients in 500 clinical sites throughout the world, including the United States, Latin America, Canada, Australia, Russia and the European Union. Amgen has gained acceptance of the study design with global regulatory authorities and enrollment is expected to begin in the second half of 2006.
At ERA-EDTA, Amgen also announced new cinacalcet HCl data from the OPTIMA Study (An OPen-label, Randomized Study Using Cinacalcet To IMprove Achievement of K/DOQI(TM) Targets in Patients with ESRD). This study showed that initiation of cinacalcet HCl at the earlier stages of secondary HPT at intact parathyroid hormone (iPTH) levels of 300-500 pg/mL enabled greater achievement of the National Kidney Foundation's (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for secondary HPT targets than if treatment was initiated at higher iPTH levels. The K/DOQI guidelines are evidence-based clinical practice guidelines for kidney dialysis patients. Additionally, cinacalcet HCl helped more patients achieve K/DOQI(TM) targets for iPTH and calcium-phosphorous product (Ca x P) levels compared to conventional therapy (with unrestricted vitamin D and phosphate binder use). Control of both PTH and Ca x P was greatest in patients with lower baseline PTH and was achieved with lower cinacalcet HCl doses.(2)
"Use of Mimpara in dialysis patients enables patients and physicians to achieve greater control of secondary HPT, especially when adequate treatment is initiated in the early stages of this progressive metabolic disorder," said Martin Wilkie, MD, Northern General Hospital, Sheffield, United Kingdom. "In our study, we found that the greatest reductions in Ca and P were in those patients receiving Mimpara in combination with lower doses of vitamin D sterols. Furthermore, large Phase 3 outcomes clinical studies are needed to determine Mimpara's benefits in improving patients' lives and preventing disease progression."
About EVOLVE and Amgen Cardiovascular Clinical Trials Program
Amgen has initiated an extensive clinical trials program to study the effect of treating CKD complications or anemia on cardiovascular outcomes in different populations. In addition to EVOLVE, Amgen initiated TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy)(TM), which is an ongoing trial in diabetic patients with chronic kidney disease and anemia not requiring dialysis, and the RED-HF(TM) Trial (Reduction of Events with Darbepoetin alfa in Heart Failure) to evaluate treatment of anemia with Aranesp on morbidity and mortality in patients with symptomatic heart failure.
About OPTIMA Data Presented At ERA-EDTA
The study involved 552 dialysis patients with baseline (BL) iPTH 300-800 pg/mL, randomized to receive either cinacalcet HCl or conventional therapy (CT) in a ratio of 2:1. Cinacalcet HCl patients were initiated at 30 mg/day and titrated to achieve iPTH Less Than or Equal to 300 pg/mL. After reaching iPTH target, vitamin D dose was decreased if necessary to achieve Ca x P target. In the CT arm, physicians had full freedom to treat patients with unrestricted vitamin D and phosphate binder use in an attempt to reach treatment targets. All patients were assessed during an efficacy assessment phase (weeks 17 to 23). More cinacalcet HCl patients with moderate BL iPTH levels (300 - 500 pg/mL) met both iPTH and Ca x P targets (65 percent) than cinacalcet HCl patients with high BL iPTH levels (500 - 800 pg/mL; 55 percent) and CT patients (16 percent). Mean daily dose of cinacalcet HCl was also lower among patients with moderate than high BL iPTH levels (42 mg vs. 60 mg).(2)
Secondary HPT, Chronic Kidney Disease and Cardiovascular Disease
There are approximately 1.3 million patients worldwide currently on dialysis to treat kidney failure(3) and nearly all of them also have secondary HPT.(4) Secondary HPT is characterized by increased levels of parathyroid hormone (PTH), calcium and phosphorus. If left untreated, patients with secondary HPT may develop severe bone disease, including bone pain and fractures.(4)
Abnormalities in PTH, calcium and phosphorus are also associated with an increased risk of hospitalization and death, often due to cardiovascular disease.(4) According to the NKF, cardiovascular disease is the leading cause of death among dialysis patients.(5)
About Sensipar/Mimpara (cinacalcet HCl)
In clinical trials in secondary HPT patients on dialysis, cinacalcet HCl was well-tolerated and effective in reducing PTH, Ca, P, Ca x P in a broad range of patients regardless of age, gender, dialysis method (hemo- or peritoneal dialysis), years on dialysis or disease severity.(6)
In a clinical trial in patients with hypercalcemia due to parathyroid carcinoma, cinacalcet HCl significantly lowered calcium levels in the majority of patients.(7)
Studies have shown that cinacalcet HCl lowers Ca, based on its mechanism of action, so it should not be initiated if a patient's Ca levels are below the lower limit of the normal range.(7) During dose titration, Ca levels should be monitored frequently and if levels decrease below the normal range, appropriate steps should be taken to increase Ca levels. The threshold for seizures may be lowered by reductions in Ca levels and, infrequently, seizures have been reported. The most commonly reported side effects are nausea and vomiting.(7)
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This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen's Form 10-K for the year ended December 31, 2005, and in Amgen's periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
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(1)Cunningham J, Danese M, Olson K, Klassen P, Chertow G.M. Kidney Int.: 1793-1800, 2005. (2)Messa P, Villa G, Braun J, et al. European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) (3)Lameire N., Jager K., van Biesen W., et al: Chronic kidney disease. Kidney Int,.68:99:30-38, 2005 (4)De Francisco AL. Clin Ther 2004; 26: 1976-1993. (5)National Kidney Foundation. Available at: http://www.kidney.org/professionals/kdoqi/guidelines_cvd/overview.htm (6)Moe SM, et al. Kidney Int.: 2005; 760-771 (7)Mimpara(R) Summary of Product Characteristics
CONTACT: Amgen, Thousand Oaks Marie Fay, 805-418-0185 (international mobile); 805-447-0081 (Thousand Oaks) Arvind Sood, 805-447-1060 (investors) SOURCE: Amgen