Phase 3 Sensipar®/Mimpara® EVOLVE™ Trial Published In The New England Journal Of Medicine

Phase 3 Sensipar®/Mimpara® EVOLVE™ Trial Published In The New England Journal
                                 Of Medicine

Study Results Simultaneously Presented at American Society of Nephrology's
Kidney Week

PR Newswire

THOUSAND OAKS, Calif., Nov. 3, 2012

THOUSAND OAKS, Calif., Nov. 3, 2012 /PRNewswire/ --Amgen (NASDAQ: AMGN) today
announced results of the Phase 3 EVOLVE™ (EValuation Of Cinacalcet HCl Therapy
to Lower CardioVascular Events) trial, which evaluated treatment with
Sensipar^®/Mimpara^® (cinacalcet) for the reduction of the risk of mortality
and cardiovascular (CV) events among 3,883 patients with secondary
hyperparathyroidism (HPT) and chronic kidney disease (CKD) receiving dialysis.
The primary endpoint of the study was time to the composite event comprising
all-cause mortality or first non-fatal CV event, including myocardial
infarction, hospitalization for unstable angina, heart failure or peripheral
vascular event. Although patients in the Sensipar/Mimpara arm experienced a
seven percent reduction in the primary endpoint (Hazard Ratio 0.93, 95 percent
CI 0.85 to 1.02, p=0.112), the results were not statistically significant, and
the trial did not meet its primary endpoint in the intent-to-treat analysis.
These data were published today in the New England Journal of Medicine and
simultaneously presented at the American Society of Nephrology's Kidney Week
(Abstract # 6450).

Baseline characteristics between the Sensipar/Mimpara and placebo groups were
generally well-balanced with the notable exception of age – an important
predictor of death and CV events. Patients in the Sensipar/Mimpara group were
one-year older than those in the placebo group (median age 55 and 54 years,
respectively). A pre-specified analysis adjusting for baseline imbalances
showed that treatment with Sensipar/Mimpara resulted in a 12 percent reduction
in the primary endpoint (Hazard Ratio 0.88, 95 percent CI 0.79 to 0.97). 

Discontinuation of investigational product was common in both arms and more
frequent in the placebo group (66.7 percent Sensipar/Mimpara versus 70.5
percent placebo). Reasons for discontinuation included kidney transplant,
parathyroidectomy, adverse events and patient request. A pre-specified
analysis, which excluded data from patients that was collected beyond six
months after stopping investigational product, showed a 15 percent reduction
in the primary endpoint (Hazard Ratio 0.85, 95 percent CI 0.76 to 0.95).

The above described pre-specified analyses, however, cannot be interpreted as

Cardiovascular disease is common among patients with CKD, including those
treated with dialysis, among whom death due to cardiovascular disease is
approximately 10 to 100-fold higher than in the general population. Secondary
HPT, a disorder which is characterized by abnormal parathyroid hormone,
calcium and phosphorus levels, has emerged as one of several complications of
CKD thought to contribute to high rates of CV events and death in the patient
population receiving dialysis.

"The EVOLVE trial is one of the largest outcomes studies ever conducted in
patients on dialysis, who are among our society's most chronically ill.
Cardiovascular disease is unacceptably high among these patients, accounting
for nearly half of all deaths. While EVOLVE did not meet its primary
endpoint, the study provides important information related to the management
of these patients," said Michael Severino, M.D., senior vice president of
Global Development and corporate chief medical officer at Amgen.

The most frequently reported adverse events in the Sensipar/Mimpara arm of the
trial were consistent with the known safety profile of this therapy and
included nausea, vomiting and hypocalcemia. As reported in the primary
manuscript, rates of serious adverse events were similar in both groups.
There were 115 and 90 neoplastic events (25 and 23 fatal) in the
Sensipar/Mimpara and placebo groups, respectively.

Sensipar/Mimpara is an oral calcimimetic agent approved for the treatment of
secondary HPT in patients with CKD receiving dialysis.

EVOLVE Trial Design
EVOLVE was an international, randomized, double-blind, placebo-controlled
Phase 3 study of 3,883 patients with secondary HPT and CKD receiving dialysis.
The trial, the largest of its kind in patients with CKD receiving dialysis,
was designed to determine if treatment with Sensipar/Mimpara, compared to
placebo, decreases the risk of all-cause mortality and CV morbidity. The
primary composite endpoint of the study was time to death or first non-fatal
cardiovascular event (myocardial infarction, hospitalization for unstable
angina, heart failure or peripheral vascular event). Secondary endpoints
included time to individual components of the primary composite endpoint,
cardiovascular mortality, stroke, bone fracture and parathyroidectomy.

The trial consisted of a 30-day screening phase, a titration phase with visits
every two weeks, and a follow-up phase with visits every eight weeks.
Following the screening phase, patients were randomized to the
Sensipar/Mimpara or placebo groups. Possible sequential doses of
Sensipar/Mimpara ^ or placebo included 30, 60, 90, 120, and 180 mg. Flexible
use of traditional therapies, such as vitamin D derivatives and phosphate
binders, were permitted in both groups.

About Secondary Hyperparathyroidism
Secondary HPT is a common and serious condition that is often progressive
among patients with CKD and it affects many of the approximately two million
people throughout the world who are receiving dialysis. The disorder develops
early as an adaptive response to declining kidney function when the
parathyroid glands (four small glands in the neck) increase the production of
parathyroid hormone (PTH) in an effort to maintain normal levels of calcium
and phosphorus. Ultimately, excess PTH production proves inadequate for
maintaining normal serum calcium and phosphorous levels. When kidney disease
progresses to the point where dialysis is needed to sustain life, secondary
HPT manifests as abnormal PTH, calcium and phosphorus levels that, in turn,
can lead to significant clinical consequences, including bone loss, skeletal
fracture and soft-tissue calcification. Although many patients with secondary
HPT are not overtly symptomatic, bone pain, particularly when standing or when
walking, achy and stiff joints, muscle weakness, and complaints of dry, itchy
skin are common. Advanced disease is marked by very large parathyroid glands
that may need to be removed by surgery.

About Sensipar/Mimpara (cinacalcet)
Cinacalcet is approved in more than 50 countries and marketed as Sensipar in
the United States (U.S.), Canada, Australia and New Zealand and as Mimpara in
the European Union and other countries. Sensipar/Mimpara is the first oral
calcimimetic agent approved for the treatment of secondary HPT in CKD patients
receiving dialysis. The therapy is also approved by the U.S. Food and Drug
Administration, European Medicines Agency and Health Canada for hypercalcemia
in patients with parathyroid carcinoma and severe hypercalcemia in patients
with primary HPT who are unable to undergo parathyroidectomy. Sensipar/Mimpara
binds to the calcium-sensing receptor, which causes the receptor to become
more sensitive to extracellular calcium ions. This results in a drop in PTH
levels by inhibiting PTH synthesis and secretion. In addition, the reductions
in PTH lower serum calcium and phosphorus levels.

Secondary HPT Indication
Sensipar is indicated for the treatment of secondary HPT in patients with CKD
on dialysis.

Important Safety Information
Sensipar lowers serum calcium; therefore, it is important that patients are
carefully monitored for the occurrence of hypocalcemia. Sensipar should not be
initiated if serum calcium is less than the lower limit of the normal range.
Significant reductions in calcium may lower the threshold for seizures. In the
treatment of secondary hyperparathyroidism the most commonly reported side
effects in clinical trials were nausea, vomiting, and diarrhea.

To see the full Sensipar Safety Information, visit

About Amgen
Amgen discovers, develops, manufactures 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, 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, bone
disease and other serious illnesses. With a deep and broad 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 vital medicines, visit Follow us on

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