THOUSAND OAKS, Calif.,
Feb. 7, 2017 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and
Drug Administration (FDA) has approved Parsabiv™ (etelcalcetide)
for the treatment of secondary hyperparathyroidism (HPT) in adult
patients with chronic kidney disease (CKD) on hemodialysis.
Parsabiv is the first therapy approved for this condition in 12
years and the only calcimimetic that can be administered
intravenously by the dialysis health care team three times a week
at the end of the hemodialysis session.
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"We are excited about today's approval of Parsabiv in the U.S.
and the opportunity to provide patients and health care providers
with a novel option to help treat a complex disease that affects a
significant number of patients on hemodialysis," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "Parsabiv not only has
demonstrated strong efficacy in clinical trials; it also fills an
unmet need by putting the delivery of the therapy in the hands of
the health care professional."
Often occurring in patients in Stage 5 of CKD,1,2
secondary HPT refers to the excessive secretion of parathyroid
hormone (PTH) by the parathyroid glands in response to decreased
renal function and impaired mineral metabolism.1,3
Parsabiv binds to and activates the calcium-sensing receptor on the
parathyroid gland, thereby causing decreases in PTH.
"As a physician who cares for patients with advanced chronic
kidney disease, I understand the importance of achieving and
maintaining simultaneous reductions in a number of complex lab
values in the treatment of secondary HPT," said Geoffrey A. Block, M.D., nephrologist at Denver
Nephrologists, PC, in Colorado.
"The ability to provide my patients with an intravenous
calcimimetic and help ensure they receive the therapy they need is
a tremendous milestone in the management of this frequently
undertreated chronic progressive disease."
Secondary HPT is a serious condition and the proportion of
patients unable to reach recommended secondary HPT lab targets has
more than doubled in the last five
years.4 Sensipar® (cinacalcet), the
first FDA-approved calcimimetic, became an important treatment for
patients with secondary HPT on dialysis based on its ability to
reduce three important biochemical abnormalities (PTH, calcium,
phosphorus). Parsabiv is a novel calcimimetic that can be
delivered intravenously at the end the hemodialysis session and has
been demonstrated to effectively reduce levels of PTH, corrected
calcium and phosphate. These reductions were maintained for up to
78 weeks.
Amgen is committed to working with patients, dialysis providers
and payers to deliver value-based solutions for managing the burden
of secondary HPT. Based on the doses expected to be used in
clinical practice, the monthly costs of Parsabiv and Sensipar
should be comparable.
Phase 3 Studies
The approval of Parsabiv in the U.S. was largely based on data from
two placebo-controlled Phase 3 studies, both of which met their
primary endpoints.
In the two 26-week, randomized, double-blind, placebo-controlled
studies, an aggregate of 1,023 patients with moderate-to-severe
secondary HPT (PTH greater than 400 pg/mL) on hemodialysis were
randomized to receive intravenous Parsabiv or placebo three times a
week, at the end of their dialysis sessions in addition to standard
of care that could include vitamin D and/or phosphate binders. The
primary endpoint of both studies was the proportion of patients
achieving greater than 30 percent reduction from baseline in PTH
during the Efficacy Assessment Phase (EAP), defined as weeks 20
through 27. Secondary endpoints included the proportion of patients
with PTH less than or equal to 300 pg/mL during the EAP; and
percent reductions in PTH, albumin-adjusted calcium (cCa),
phosphate (P) and cCa x P during the EAP.
The two studies showed that significantly more Parsabiv than
placebo patients, respectively, achieved:
- A greater than 30 percent reduction from baseline in PTH during
the EAP: 77 percent versus 11 percent in Study 1, and 79 percent
versus 11 percent in Study 2
- PTH levels of 300 pg/mL or less during the EAP: 52 percent
versus 6 percent in Study 1, and 56 percent versus 5 percent in
Study 2
Additionally, greater percent reduction from baseline was
achieved in Parsabiv-treated patients than placebo-treated patients
during the EAP, for PTH, corrected calcium and phosphate in both
studies.
In a pooled analysis of the two Phase 3 placebo-controlled
studies, asymptomatic reductions in serum calcium and symptomatic
hypocalcemia occurred more frequently in patients treated with
Parsabiv compared to placebo (64 percent versus 10 percent, and 7
percent versus 0.2 percent, respectively). Other commonly reported
adverse reactions were muscle spasms (12 percent versus 7 percent),
diarrhea (11 percent versus 9 percent), nausea (11 percent versus 6
percent), vomiting (9 percent versus 5 percent), headache (8
percent versus 6 percent), and paresthesia/hypoesthesia (6 percent
versus 1 percent).
About Secondary Hyperparathyroidism
Secondary hyperparathyroidism (HPT) is a chronic and serious
condition which affects many of the approximately two million
people throughout the world who are receiving dialysis, including
468,000 people in the U.S.5,6,7,8 Approximately 88
percent of CKD patients on hemodialysis will develop secondary
HPT.9 Secondary HPT refers to the excessive secretion of
parathyroid hormone (PTH) by the parathyroid glands in response to
decreased renal function and impaired mineral
metabolism.1,3 The elevated levels of PTH can lead to an
increase in the release of calcium and phosphate from the
bones.3,10,11 Secondary HPT is often initially silent
and asymptomatic.3 As a result, secondary HPT is
frequently underdiagnosed and undertreated.3,12
About Parsabiv™ (etelcalcetide) in the U.S.
Parsabiv is a novel calcimimetic agent indicated for the treatment
of secondary hyperparathyroidism (HPT) in adult patients with
chronic kidney disease (CKD) on hemodialysis.
Parsabiv has not been studied in adult patients with parathyroid
carcinoma, primary hyperparathyroidism, or with CKD who are not on
hemodialysis and is not recommended for use in these
populations.
A calcimimetic is a drug that mimics the action of calcium by
activating the calcium-sensing receptors on the parathyroid gland.
Parsabiv binds to and activates the calcium-sensing receptor on the
parathyroid gland, thereby decreasing PTH levels.
Parsabiv Important Safety Information in the U.S.
Contraindication: Parsabiv™ is contraindicated in patients
with known hypersensitivity to etelcalcetide or any of its
excipients. Hypersensitivity reactions, including pruritic rash,
urticaria, and face edema, have occurred.
Hypocalcemia: Parsabiv™ lowers serum calcium and can lead
to hypocalcemia, sometimes severe. Significant lowering of serum
calcium can cause QT interval prolongation and ventricular
arrhythmia. Patients with conditions that predispose to QT
interval prolongation and ventricular arrhythmia may be at
increased risk for QT interval prolongation and ventricular
arrhythmias if they develop hypocalcemia due to Parsabiv. Closely
monitor corrected serum calcium and QT interval in patients at risk
on Parsabiv™.
Significant reductions in corrected serum calcium may lower the
threshold for seizures. Patients with a history of seizure disorder
may be at increased risk for seizures if they develop hypocalcemia
due to Parsabiv™. Monitor corrected serum calcium in
patients with seizure disorders on Parsabiv™.
Concurrent administration of Parsabiv™ with another oral
calcimimetic could result in severe, life-threatening hypocalcemia.
Patients switching from cinacalcet to Parsabiv™ should discontinue
cinacalcet for at least 7 days prior to initiating Parsabiv™.
Closely monitor corrected serum calcium in patients receiving
Parsabiv™ and concomitant therapies known to lower serum
calcium.
Measure corrected serum calcium prior to initiation of
Parsabiv™. Do not initiate in patients if the corrected serum
calcium is less than the lower limit of normal. Monitor corrected
serum calcium within 1 week after initiation or dose adjustment and
every 4 weeks during treatment with Parsabiv™. Measure PTH 4
weeks after initiation or dose adjustment of Parsabiv™. Once the
maintenance dose has been established, measure PTH per clinical
practice.
Worsening Heart Failure: In Parsabiv™ clinical studies,
cases of hypotension, congestive heart failure, and decreased
myocardial performance have been reported. Closely monitor patients
treated with Parsabiv™ for worsening signs and symptoms of heart
failure.
Upper Gastrointestinal Bleeding: In clinical studies, 2
patients treated with Parsabiv™ in 1253 patient years of exposure
had upper gastrointestinal (GI) bleeding at the time of death. The
exact cause of GI bleeding in these patients is unknown and there
were too few cases to determine whether these cases were related to
Parsabiv™.
Patients with risk factors for upper GI bleeding, such as known
gastritis, esophagitis, ulcers or severe vomiting, may be at
increased risk for GI bleeding with Parsabiv™. Monitor patients for
worsening of common Parsabiv™ GI adverse reactions and for signs
and symptoms of GI bleeding and ulcerations during Parsabiv™
therapy.
Adynamic Bone: Adynamic bone may develop if PTH levels
are chronically suppressed.
Adverse Reactions: In clinical trials of patients with
secondary HPT comparing Parsabiv™ to placebo, the most common
adverse reactions were blood calcium decreased (64% vs. 10%),
muscle spasms (12% vs. 7%), diarrhea (11% vs. 9%), nausea (11% vs
6%), vomiting (9% vs 5%), headache (8% vs 6%), hypocalcemia (7% vs
0.2%), and paresthesia (6% vs 1%).
Please see Parsabiv™ Full Prescribing
Information.
About Sensipar® (cinacalcet) in the U.S.
Sensipar is the first oral calcimimetic agent approved by the FDA
for the treatment of secondary HPT in adult patients with CKD on
dialysis. Sensipar is not indicated for use in adult patients with
CKD who are not on dialysis because of an increased risk of
hypocalcemia. The therapy is also approved in the U.S. for
treatment of hypercalcemia in adult patients with parathyroid
carcinoma and hypercalcemia in adult patients with primary
hyperparathyrodisim (HPT) for whom parathyroidectomy would be
indicated on the basis of serum calcium levels, but who are unable
to undergo parathyroidectomy. Sensipar binds to the calcium-sensing
receptor, resulting in a drop in PTH levels by inhibiting PTH
synthesis and secretion. The reduction in PTH is associated with a
concomitant decrease in serum calcium levels.
Sensipar Important Safety Information in the U.S.
Sensipar® (cinacalcet) treatment initiation is
contraindicated if serum calcium is less than the lower limit of
the normal range (8.4 mg/dL).
Sensipar® lowers serum calcium; therefore, it is
important that patients are carefully monitored for the occurrence
of hypocalcemia. Life threatening events and fatal outcomes
associated with hypocalcemia have been reported in patients treated
with Sensipar®, including pediatric patients. Decreases
in serum calcium can prolong the QT interval, potentially resulting
in ventricular arrhythmia. Cases of QT prolongation and ventricular
arrhythmia secondary to hypocalcemia have been reported in patients
treated with Sensipar®.
Significant reductions in calcium may lower the threshold for
seizures. Patients, particularly those with a history of seizure
disorder, should be carefully monitored for the occurrence of low
serum calcium or symptoms of hypocalcemia.
In Sensipar® postmarketing use, isolated,
idiosyncratic cases of hypotension, worsening heart failure, and/or
arrhythmia were reported in patients with impaired cardiac
function. The causal relationship to
Sensipar® therapy could not be completely excluded
and may be mediated by reductions in serum calcium levels.
Adynamic bone disease may develop if intact parathyroid hormone
(iPTH) levels are suppressed below 100 pg/mL. Patients with
moderate to severe hepatic impairment should be monitored
throughout treatment with Sensipar®, as cinacalcet
exposure assessed by area under the curve (AUC) was higher than in
patients with normal hepatic function.
Patients with secondary HPT: Serum calcium and serum phosphorous
should be measured within 1 week and PTH should be measured 1 to 4
weeks after initiation or dose adjustment of Sensipar®.
Once the maintenance dose has been established, serum calcium and
serum phosphorous should be measured approximately monthly, and PTH
every 1 to 3 months. Patients with primary HPT or parathyroid
carcinoma: Serum calcium should be measured within 1 week after
initiation or dose adjustment of Sensipar®. Once
maintenance dose levels have been established, serum calcium should
be measured every 2 months.
In clinical trials of patients with secondary HPT comparing
Sensipar® to placebo, the most commonly reported
side effects were nausea (31 percent vs. 19 percent), vomiting (27
percent vs. 15 percent), and diarrhea (21 percent vs. 20 percent).
In clinical trials of patients with primary HPT and parathyroid
carcinoma treated with Sensipar®, the most commonly
reported side effects were nausea (63 percent), vomiting (46
percent), and paresthesia (20 percent).
Please see Sensipar® Full Prescribing
Information.
About Amgen
Amgen is committed to unlocking the potential of biology for
patients suffering from serious illnesses by discovering,
developing, manufacturing and delivering innovative human
therapeutics. This approach begins by using tools like advanced
human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages
its expertise to strive for solutions that improve health outcomes
and dramatically improve people's lives. A biotechnology pioneer
since 1980, Amgen has grown to be one of the world's leading
independent biotechnology companies, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
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Accessed December 20, 2016.
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