-- 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). Cinalcalet
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)
About Amgen
Amgen discovers, develops and delivers innovative human
therapeutics. A biotechnology pioneer since 1980, Amgen was one of the
first companies to realize the new science's promise by bringing safe
and effective medicines from lab, to manufacturing plant, to patient.
Amgen therapeutics have changed the practice of medicine, helping
millions of people around the world in the fight against cancer,
kidney disease, rheumatoid arthritis, and other serious illnesses.
With a broad and deep pipeline of potential new medicines, Amgen
remains committed to advancing science to dramatically improve
people's lives. To learn more about our pioneering science and our
vital medicines, visit www.amgen.com.
Forward-Looking Statement
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.
No forward-looking statement can be guaranteed and actual results
may differ materially from those we project. Discovery or
identification of new product candidates or development of new
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and become a
commercial product. Further, preclinical results do not guarantee safe
and effective performance of product candidates in humans. The
complexity of the human body cannot be perfectly, or sometimes, even
adequately modeled by computer or cell culture systems or animal
models. The length of time that it takes for us to complete clinical
trials and obtain regulatory approval for product marketing has in the
past varied and we expect similar variability in the future. We
develop product candidates internally and through licensing
collaborations, partnerships and joint ventures. Product candidates
that are derived from relationships may be subject to disputes between
the parties or may prove to be not as effective or as safe as we may
have believed at the time of entering into such relationship. Also, we
or others could identify side effects or manufacturing problems with
our products after they are on the market. In addition, sales of our
products are affected by the availability of reimbursement and the
reimbursement policies imposed by third party payors, including
governments, private insurance plans and managed care providers, and
may be affected by domestic and international trends toward managed
care and healthcare cost containment as well as possible U.S.
legislation affecting pharmaceutical pricing and reimbursement.
Government regulations and reimbursement policies may affect the
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We believe that some of our newer products, product candidates or new
indications for existing products, may face competition when and as
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Our stock price may be affected by actual or perceived market
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related to our product candidates is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and Drug
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regarding the safety or effectiveness of the product candidates. Only
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for our products is preliminary and investigative and is not part of
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discussed in this news release.
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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
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