November 16, 2015 11:26am EST
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VARUBI™(rolapitant) provides extended protection for
chemotherapy-induced nausea and vomiting (CINV) in the delayed phase
(25-120 hours) with a single dose as part of an antiemetic regimen
More than half of patients undergoing emetogenic chemotherapy may
experience delayed CINV, even when prescribed a 5-HT 3
receptor antagonist and a corticosteroid
MIAMI--(BUSINESS WIRE)--
OPKO Health Inc. (NYSE: OPK), today announced that VARUBI™ (rolapitant),
an NK-1 receptor antagonist, is now available in the United States. The
U.S. Food and Drug Administration (FDA) approved VARUBI on Sept. 1,
2015, for use in combination with other antiemetic agents in adults for
the prevention of delayed nausea and vomiting associated with initial
and repeat courses of emetogenic cancer chemotherapy, including, but not
limited to, highly emetogenic chemotherapy.
VARUBI is a selective and competitive antagonist of human substance
P/neurokinin 1 (NK-1) receptors, with a plasma half-life of
approximately seven days. Results from all three Phase 3 trials of
VARUBI demonstrated that patients receiving highly and moderately
emetogenic chemotherapy agents, including platinum and
anthracycline/cyclophosphamide-containing regimens, experienced a
significant reduction in episodes of vomiting or use of rescue
medication during the 25 to 120 hour period following chemotherapy
administration. In addition, patients who received VARUBI reported
experiencing less nausea that interfered with normal daily life and
fewer episodes of vomiting or retching over multiple cycles of
chemotherapy. No dosage adjustment is required for dexamethasone, a
CYP3A4 substrate, when administering VARUBI. A single dose (two 90
milligram tablets) of VARUBI is to be administered approximately one to
two hours prior to chemotherapy administration, in combination with a
5-HT 3 receptor antagonist and dexamethasone.
Just three weeks after the approval of VARUBI by the U.S. FDA, the
National Comprehensive Cancer Network (NCCN) added VARUBI to the NCCN
Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Antiemesis
Version 2.2015 as a recommended option, in combination with other
antiemetic agents, for patients receiving both high emetic risk
intravenous chemotherapy (HEC) and moderate emetic risk intravenous
chemotherapy (MEC). Category 1, the highest level category of evidence
and consensus, was granted to VARUBI for both HEC and MEC chemotherapy.
The full prescribing information for VARUBI is available at www.VarubiRx.com .
About Chemotherapy-Induced Nausea and Vomiting (CINV)
Chemotherapy-induced nausea and vomiting is a debilitating, yet often
preventable, side effect of chemotherapy.
Up to 50% of patients undergoing highly or moderately emetogenic
chemotherapy experience delayed CINV (25 to 120 hours post
chemotherapy)—even when prescribed a 5-HT 3 receptor
antagonist and corticosteroid.
Blocking both 5-HT 3 and NK-1 receptors has been shown to
offer better control of nausea and vomiting than inhibiting 5-HT 3
receptors alone. Adding a single dose of VARUBI to an antiemetic
regimen, including a 5-HT 3 receptor antagonist and
corticosteroid, further improves prevention of CINV in the delayed phase
following chemotherapy.
About VARUBI™
VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist
indicated in combination with other antiemetic agents in adults for the
prevention of delayed nausea and vomiting associated with initial and
repeat courses of emetogenic cancer chemotherapy, including, but not
limited to, highly emetogenic chemotherapy. NK-1 receptors are highly
concentrated in the brain and bind neurokinin substance P. Activation of
NK-1 receptors plays a central role in nausea and vomiting induced by
emetogenic stimuli, including certain cancer chemotherapies. A Positron
Emission Tomography (PET) study with rolapitant in normal, healthy
volunteers demonstrated that rolapitant crosses the blood brain barrier
and occupies brain NK-1 receptors at high levels for up to 120 hours.
VARUBI has a half-life of approximately seven days, which may contribute
to the ability of a single dose of VARUBI to cover the entire delayed
CINV phase (25-120 hours).
An intravenous formulation of rolapitant is also being developed. TESARO
licensed exclusive rights for the development, manufacture,
commercialization, and distribution of VARUBI (rolapitant) from OPKO
Health, Inc.
About the VARUBI (Rolapitant) Clinical Program
The superior efficacy of VARUBI was established in multiple global,
randomized, well-controlled, blinded clinical trials that enrolled more
than 2,500 patients. VARUBI, when administered in combination with a 5-HT 3
receptor antagonist and dexamethasone, was significantly superior to a
5-HT 3 receptor antagonist and dexamethasone in preventing
delayed CINV in patients receiving either moderately or highly
emetogenic chemotherapy.
The clinical profile of VARUBI in cisplatin-based, highly emetogenic
chemotherapy (HEC) was confirmed in two identical Phase 3 studies: HEC1
and HEC2. Both trials met their primary endpoint of complete response
(CR) in the delayed phase (25-120 hours) of CINV and demonstrated
statistical superiority of rolapitant 180 mg compared to active control
(5-HT 3 receptor antagonist + dexamethasone). In HEC1, 264
patients received rolapitant 180 mg, and 262 received control. The
proportion of patients achieving a CR was 72.7% vs. 58.4% (p= < 0.001).
In HEC2, 271 patients received rolapitant, and 273 received control. The
proportion of patients achieving a CR was 70.1% vs. 61.9% (p=0.043). The
most common adverse reactions (≥3%) among patients receiving
cisplatin-based chemotherapy were neutropenia (9% VARUBI vs. 8%
control), hiccups (5% vs. 4%), and abdominal pain (3% vs. 2%).
A Phase 3 trial was also conducted to evaluate rolapitant 180 mg
compared to active control in 1,332 patients receiving
anthracycline/cyclophosphamide combinations or moderately emetogenic
chemotherapy regimens, including carboplatin, irinotecan, pemetrexed,
oxaliplatin, and doxorubicin. This trial met its primary endpoint of CR
in the delayed phase of CINV and demonstrated statistical superiority of
rolapitant 180 mg compared to active control (5-HT 3 receptor
antagonist + dexamethasone). The proportion of patients achieving a CR
was 71.3% vs 61.6% (p= < 0.001). The most common adverse reactions (≥3%)
among patients receiving these chemotherapies were decreased appetite
(9% VARUBI vs. 7% control), neutropenia (7% vs. 6%), dizziness (6% vs.
4%), dyspepsia (4% vs. 2%), urinary tract infection (4% vs. 3%),
stomatitis (4% vs. 2%), and anemia (3% vs. 2%).
Primary data from the three Phase 3 studies have been published in Lancet
Oncology. The analysis of the non-AC MEC population was presented at
the 2015 annual meeting for the Multinational Association for Supportive
Care in Cancer, and commentary has been provided in Nature Reviews
Clinical Oncology .
Indication and Important Safety Information for VARUBI™ (Rolapitant)
Indication
VARUBI, in combination with other antiemetic agents, is indicated in
adults for the prevention of delayed nausea and vomiting associated with
initial and repeat courses of emetogenic cancer chemotherapy, including,
but not limited to, highly emetogenic chemotherapy.
Contraindication
VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6
substrate. A significant increase in plasma concentrations of
thioridazine may result in QT prolongation and Torsades de Pointes.
Warnings and precautions
Interaction with CYP2D6 substrates with a narrow therapeutic index
The inhibitory effect of VARUBI on CYP2D6 lasts for at least 7 days
and may last longer after administration of a single dose of VARUBI.
Avoid use of VARUBI in patients who are receiving pimozide, a CYP2D6
substrate. An increase in plasma concentrations of pimozide may result
in QT prolongation.
Monitor for adverse reactions if concomitant use of VARUBI and other
CYP2D6 substrates with a narrow therapeutic index cannot be avoided.
Adverse reactions
In patients receiving cisplatin-based, highly emetogenic chemotherapy
in cycle 1, the most common adverse reactions reported at an incidence
of ≥5% and a frequency greater than control were neutropenia (9%
VARUBI vs 8% control) and hiccups (5% vs 4%).
In patients receiving moderately emetogenic chemotherapy and
combinations of anthracycline and cyclophosphamide in cycle 1, the
most common adverse reactions reported at an incidence of ≥5% and a
frequency greater than control were decreased appetite (9% VARUBI vs
7% control), neutropenia (7% vs 6%), and dizziness (6% vs 4%).
Drug interactions
VARUBI is an inhibitor of breast cancer resistance protein (BCRP) and
P-glycoprotein (P-gp). Increased plasma concentrations of BCRP and
P-gp substrates with a narrow therapeutic index may result in
potential adverse reactions. Monitor for adverse reactions related to
the concomitant drug if use with VARUBI cannot be avoided
Avoid use of VARUBI in patients who require chronic administration of
strong CYP3A4 inducers (e.g., rifampin) as significantly reduced
plasma concentrations of VARUBI can decrease the efficacy of VARUBI
VARUBI is available by prescription only.
About OPKO Health
OPKO Health, Inc. is a diversified healthcare company that seeks to
establish industry-leading positions in large, rapidly growing markets.
Our diagnostics business includes Bio-Reference Laboratories, the
nation’s third-largest clinical laboratory with a core genetic testing
business and a 420-person salesforce to drive growth and leverage new
products, including the 4Kscore® prostate cancer test and the Claros®1
in-office immunoassay platform. Our pharmaceutical business features
Rayaldee™, a treatment for secondary hyperparathyroidism in stage 3-4
chronic kidney disease patients with vitamin D deficiency (March 29,
2016 PDUFA date) and VARUBI™ for chemotherapy-induced nausea and
vomiting (oral formulation approved by FDA and pending launch by partner
Tesaro, IV formulation in Phase 3). Our biologics business includes
hGH-CTP, a once-weekly human growth hormone injection (in Phase 3 and
partnered with Pfizer), and a long-acting Factor VIIa drug for
hemophilia (entering Phase 2a). We also have production and distribution
assets worldwide, multiple strategic investments and an active business
development strategy. More information is available at www.opko.com .
SAFE HARBOR STATEMENT
This press release contains "forward-looking statements," as that term
is defined under the Private Securities Litigation Reform Act of 1995
(PSLRA), which statements may be identified by words such as "expects,"
"plans," "projects," "will," "may," "anticipates," "believes," "should,"
"intends," "estimates," and other words of similar meaning, including
statements regarding the commercial availability of VARUBI in the U.S.
and TESARO's plans to develop and commercialize additional therapies, as
well as other non-historical statements about our expectations, beliefs
or intentions regarding our business, technologies and products,
financial condition, strategies or prospects. Many factors could cause
our actual activities or results to differ materially from the
activities and results anticipated in forward-looking statements. These
factors include those described in our filings with the Securities and
Exchange Commission, as well as the risks inherent in funding,
developing and obtaining regulatory approvals of new,
commercially-viable and competitive products and treatments. In
addition, forward-looking statements may also be adversely affected by
general market factors, competitive product development, product
availability, federal and state regulations and legislation, the
regulatory process for new products and indications, manufacturing
issues that may arise, patent positions and litigation, among other
factors. The forward-looking statements contained in this press release
speak only as of the date the statements were made, and we do not
undertake any obligation to update forward-looking statements. We intend
that all forward-looking statements be subject to the safe-harbor
provisions of the PSLRA.
View source version on businesswire.com: http://www.businesswire.com/news/home/20151116006072/en/
OPKO Health, Inc.
Tara Mackay, 305-575-4100
Investor Relations
or
Media
Rooney
& Associates
Terry Rooney, 212-223-0689
or
Marion
Janic, 212-223-4017
or
Investors
LHA
Anne
Marie Fields, 212-838-3777
or
Bruce
Voss, 310-691-7100
Source: OPKO Health, Inc.
Released November 16, 2015
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