Companies to co-promote newly-approved statin LIVALO in the U.S.
market Lilly licenses LIVALO commercialization rights for Latin
America INDIANAPOLIS and MONTGOMERY, Ala., Dec. 23
/PRNewswire-FirstCall/ -- Eli Lilly and Company (NYSE:LLY), Kowa
Company, Limited, and Kowa's U.S. subsidiary, Kowa Pharmaceuticals
America, Inc., today announced that Lilly and Kowa Pharmaceuticals
America have entered into a co-promotion agreement in the United
States to commercialize LIVALO® (pitavastatin). Lilly and Kowa have
also entered into a licensing agreement in Latin America. LIVALO is
a statin approved by the U.S. Food and Drug Administration (FDA) in
August 2009 for the treatment of primary hyperlipidemia and mixed
dyslipidemia. Under the terms of the agreements, Kowa
Pharmaceuticals America will receive an undisclosed upfront
payment. Lilly and Kowa Pharmaceuticals America will co-promote
LIVALO in the U.S. market, with both companies providing sales
force resources and sharing development and marketing costs. Kowa
Pharmaceuticals America will record all U.S. sales of LIVALO and
will pay Lilly an escalating co-promotion fee based on the level of
annual net sales. In addition, Lilly has acquired an exclusive
license from Kowa to commercialize LIVALO in Latin American
markets, including Mexico, Central America and South America.
Additional deal terms were not disclosed. "We are pleased to
partner with Kowa to help bring this new statin to market and
provide patients a new option to help control their cholesterol,"
said John Lechleiter, Ph.D., Lilly chairman and chief executive
officer. "Our co-promotion arrangement in the U.S. and licensing
arrangement in Latin America will allow Lilly to expand our product
offerings in the cardiovascular therapeutic area and more
efficiently utilize our existing cardiovascular sales force."
"Physicians are challenged by some patients who do not always do
well on their current statin therapy, and who also must deal with
potential interactions with other medications. LIVALO offers a new
statin option, with LDL lowering consistent with the commonly
administered doses of Lipitor® and Zocor®, and significantly
greater LDL lowering in the elderly compared to Pravachol®," stated
LeRoy LeNarz, M.D., senior medical director at Lilly. "It is with
great pleasure that we partner with an internationally-renowned
company like Lilly," said Yoshihiro Miwa, Kowa president and CEO.
"With a joint effort by Lilly, Kowa and Kowa Pharmaceuticals
America, we hope to pave the way for the efficient market entry and
establish a presence with LIVALO in the statin market in the U.S.
and Latin America." "We are excited to partner with Lilly as we
work to establish the LIVALO brand and expand Kowa Pharmaceuticals
America's presence in the U.S. market," said Ben Stakely, president
and CEO of Kowa Pharmaceuticals America. About LIVALO LIVALO is a
fully synthetic statin originating from Japan. The efficacy of
LIVALO has been evaluated against atorvastatin, simvastatin, and
pravastatin in patients with primary hyperlipidemia or mixed
dyslipidemia. In these studies, LIVALO effectively reduced LDL-C,
including in patients with diabetes, the elderly, and patients with
2 or more risk factors for coronary artery disease. Unlike many
statins, LIVALO is only minimally metabolized by the liver
Cytochrome P450 enzyme system, suggesting that the potential for
clinically significant drug interactions between LIVALO and drugs
that inhibit or that are metabolized by CYP450 enzymes, including
warfarin, would be reduced. Since its launch in Japan, South Korea,
Thailand and China, LIVALO has been successfully used in these
countries to treat hypercholesterolemia and familial
hypercholesterolemia, and has accumulated millions of patient-years
of exposure. In Japan, sales of LIVALO for fiscal year 2008 reached
34 billion yen (approximately $380 million) and its market share
was about 12%. About Dyslipidemia and Hypercholesterolemia
Dyslipidemia refers to abnormal levels of fatty substances in the
blood, or a disorder of the production or breakdown process of
lipoprotein. Dyslipidemia may be marked by an elevation of total
cholesterol, LDL-C, and triglyceride (TG) concentrations and a
decrease in HDL-C in the blood. An elevated level of cholesterol in
the blood is called hypercholesterolemia, commonly referred to as
high cholesterol. LDL-C lowering is well established as one of the
strongest independent predictors of cardiovascular morbidity and
mortality. Despite the availability of treatments in the U.S.,
there is still a need for better control of and treatment for
dyslipidemia. According to the American Heart Association,
approximately one out of every three American adults has an LDL
cholesterol level of 130mg/dL or higher, which is a major risk
factor for coronary heart disease (CHD) and stroke. In addition,
less than half of patients who qualify for any kind of
lipid-modifying treatment for CHD risk reduction are receiving it,
and only about one-third of patients who are on treatment are
achieving their LDL goals. IMPORTANT SAFETY INFORMATION ABOUT
LIVALO® (PITAVASTATIN) TABLETS INDICATIONS AND USAGE Drug therapy
should be one component of multiple-risk-factor intervention in
individuals who require modifications of their lipid profile.
Lipid-altering agents should be used in addition to a diet
restricted in saturated fat and cholesterol only when the response
to diet and other nonpharmacological measures has been inadequate.
LIVALO is a HMG-CoA reductase inhibitor indicated as an adjunctive
therapy to diet to reduce elevated total cholesterol (TC),
low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo
B), triglycerides (TG), and to increase HDL-C in adult patients
with primary hyperlipidemia or mixed dyslipidemia. Limitations of
Use: Doses of LIVALO greater than 4 mg once daily were associated
with an increased risk for severe myopathy in premarketing clinical
studies. Do not exceed 4 mg once daily dosing of LIVALO. The effect
of LIVALO on cardiovascular morbidity and mortality has not been
determined. LIVALO has not been studied in patients with severe
renal impairment (glomerular filtration rate < 30 mL/min/1.73
m2) not on hemodialysis. LIVALO should not be used in this patient
population. LIVALO has not been studied with the protease inhibitor
combination lopinavir/ritonavir. LIVALO should not be used with
this combination of protease inhibitors. LIVALO has not been
studied in Fredrickson Type I, III, and V dyslipidemias. General
Dosing Information: The dose range for LIVALO is 1 to 4 mg orally
once daily at any time of the day with or without food. The
recommended starting dose is 2 mg and the maximum dose is 4 mg. The
starting dose and maintenance doses of LIVALO should be
individualized according to patient characteristics, such as goal
of therapy and response. After initiation or upon titration of
LIVALO, lipid levels should be analyzed after 4 weeks and the
dosage adjusted accordingly. Dosage in Patients with Renal
Impairment: Patients with moderate renal impairment (glomerular
filtration rate 30 to < 60 mL/min/1.73 m2) and end -stage renal
disease receiving hemodialysis should receive a starting dose of
LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once
daily. LIVALO should not be used in patients with severe renal
impairment (glomerular filtration rate < 30 mL/min/1.73 m2) In
patients taking erythromycin, a dose of LIVALO 1 mg once daily
should not be exceeded. In patients taking rifampin, a dose of
LIVALO 2 mg once daily should not be exceeded. CONTRAINDICATIONS
The use of LIVALO is contraindicated in the following conditions:
-- Patients with a known hypersensitivity to any component of this
product. Hypersensitivity reactions including rash, pruritus, and
urticaria have been reported with LIVALO. -- Patients with active
liver disease which may include unexplained persistent elevations
of hepatic transaminase levels -- Women who are pregnant or may
become pregnant. Because HMG-CoA reductase inhibitors decrease
cholesterol synthesis and possibly the synthesis of other
biologically active substances derived from cholesterol, LIVALO may
cause fetal harm when administered to pregnant women. Additionally,
there is no apparent benefit to therapy during pregnancy, and
safety in pregnant women has not been established. If the patient
becomes pregnant while taking this drug, the patient should be
apprised of the potential hazard to the fetus and the lack of known
clinical benefit with continued use during pregnancy. -- Nursing
mothers. Animal studies have shown that LIVALO passes into breast
milk. Since HMG-CoA reductase inhibitors have the potential to
cause serious adverse reactions in nursing infants, LIVALO, like
other HMG-CoA reductase inhibitors, is contraindicated in pregnant
or nursing mothers. -- Co-administration with cyclosporine.
WARNINGS AND PRECAUTIONS Skeletal Muscle Effects: Cases of myopathy
and rhabdomyolysis with acute renal failure secondary to
myoglobinuria have been reported with HMG-CoA reductase inhibitors,
including LIVALO. These risks can occur at any dose level, but
increase in a dose-dependent manner. LIVALO should be prescribed
with caution in patients with predisposing factors for myopathy.
These factors include advanced age (>65 years), renal
impairment, and inadequately treated hypothyroidism. The risk of
myopathy may also be increased with concurrent administration of
fibrates or lipid-modifying doses of niacin. LIVALO should be
administered with caution in patients with impaired renal function,
in elderly patients, or when used concomitantly with fibrates or
lipid-modifying doses of niacin. LIVALO therapy should be
discontinued if markedly elevated creatine kinase (CK) levels occur
or myopathy is diagnosed or suspected. LIVALO therapy should also
be temporarily withheld in any patient with an acute, serious
condition suggestive of myopathy or predisposing to the development
of renal failure secondary to rhabdomyolysis (e.g., sepsis,
hypotension, dehydration, major surgery, trauma, severe metabolic,
endocrine, and electrolyte disorders, or uncontrolled seizures).
All patients should be advised to promptly report unexplained
muscle pain, tenderness, or weakness, particularly if accompanied
by malaise or fever. Liver Enzyme Abnormalities and Monitoring:
Increases in serum transaminases (aspartate aminotransferase
[AST]/serum glutamic-oxaloacetic transaminase, or alanine
aminotransferase [ALT]/serum glutamic-pyruvic transaminase) have
been reported with HMG-CoA reductase inhibitors, including LIVALO.
In most cases, the elevations were transient and resolved or
improved on continued therapy or after a brief interruption in
therapy. In placebo-controlled Phase 2 studies, ALT >3 times the
upper limit of normal was not observed in the placebo, LIVALO 1 mg,
or LIVALO 2 mg groups. One out of 202 patients (0.5%) administered
LIVALO 4 mg had ALT >3 times the upper limit of normal. It is
recommended that liver enzyme tests be performed before and at 12
weeks following both the initiation of therapy and any elevation of
dose and periodically (e.g., semiannually) thereafter. Patients who
develop increased transaminase levels should be monitored until the
abnormalities have resolved. Should an increase in ALT or AST of
>3 times upper limit of normal persist, reduction of dose or
withdrawal of LIVALO is recommended. As with other HMG-CoA
reductase inhibitors, LIVALO should be used with caution in
patients who consume substantial quantities of alcohol. Active
liver disease, which may include unexplained persistent
transaminase elevations, is a contraindication to the use of
LIVALO. ADVERSE REACTIONS: The following serious adverse reactions
are discussed in greater detail in the full prescribing
information: -- rhabdomyolysis (a serious muscle disorder) with
myoglobinuria (a laboratory test result), and acute renal (kidney)
failure and myopathy including myositis (muscular pains), and --
liver enzyme abnormalities (a laboratory test result). In
controlled clinical trials of up to 12 weeks duration adverse
reactions were infrequent, the common adverse reactions, including
their MedDRA and common names, reported by 2% or more of treated
patients are: back pain, constipation or diarrhea, myalgia
(muscular pain), and pain in the extremities (pain in arms or
legs). Other adverse reactions reported from clinical studies were
arthralgia (joint pain), headache, influenza (the flu), and
nasopharyngitis (common cold). The following laboratory
abnormalities have also been reported: elevated creatine
phosphokinase, transaminases, alkaline phosphatase, bilirubin, and
glucose. In controlled clinical studies and their open-label
extensions, 3.9% (1 mg), 3.3% (2 mg), and 3.7% (4 mg) of
pitavastatin-treated patients were discontinued due to adverse
reactions. The most common adverse reactions that led to treatment
discontinuation were: elevated creatine phosphokinase (0.6% on 4
mg) and myalgia (0.5% on 4 mg). DRUG INTERACTIONS: As with other
statin medications there is a chance of certain drug interactions
while taking LIVALO. Caution is advised. The physician should
consult the full prescribing information regarding suggested dose
reductions or avoidance of LIVALO therapy when coadminstration of
any of the following is being considered: -- the AIDS drugs,
lopinavir and ritonavir. LIVALO should not be used with this drug
combination, -- the antibiotics, erythromycin and rifampin. A
LIVALO dose reduction may be indicated. -- the cholesterol drugs,
fibrates and niacin. A LIVALO dose reduction may be indicated.
While taking LIVALO, the patient should be advised not to start
taking any of these medicines without speaking to their doctor or
pharmacist first. Additional drug-drug pharmacokinetic interaction
studies were conducted; the results of these studies are tabulated
in the full prescribing information. PATIENT COUNSELING INFORMATION
The patient should be informed of the following: Dosing Time:
LIVALO can be taken at any time of day with or without food. Muscle
Pain: Patients should be advised to promptly notify their physician
of any unexplained muscle pain, tenderness, or weakness. They
should discuss all medication, both prescription and over the
counter, with their physician. Pregnancy: Women of childbearing age
should use an effective method of birth control to prevent
pregnancy while using LIVALO. Discuss future pregnancy plans with
your healthcare professional, and discuss when to stop LIVALO if
you are trying to conceive. If you are pregnant, stop taking LIVALO
and call your healthcare professional. Breastfeeding: Women who are
breastfeeding should not use LIVALO. If you have a lipid disorder
and are breastfeeding, stop taking LIVALO and consult with your
healthcare professional. Liver Enzymes: It is recommended that
liver enzymes be checked before and at 12 weeks following both the
initiation of therapy and any elevation of dose, and periodically
(e.g., semiannually) thereafter. For complete product prescribing
information you should consult the current LIVALO (pitavastatin)
package insert which may be found on the Kowa Pharmaceuticals
America, Inc. web page at
http://www.kowapharma.com/companyLivalo.htm About Kowa Company,
Ltd. and Kowa Pharmaceuticals America, Inc. Kowa Company, Ltd. is a
privately held multinational company headquartered in Nagoya,
Japan. Established in 1894, Kowa is actively engaged in various
manufacturing and trading activities in the fields of
pharmaceutical, life science, information technology, textiles,
machinery and various consumer products. Kowa's pharmaceutical
division is focused on cardiovascular therapeutics. In the US, Kowa
has two subsidiaries in the pharmaceutical business, Kowa
Pharmaceuticals America, Inc. and Kowa Research Institute, Inc.,
located in the Research Triangle Park area of North Carolina and
responsible for the clinical development of Kowa's drug candidates.
Kowa Pharmaceuticals America, Inc. is a specialty pharmaceutical
company focused primarily in the area of cardiometabolic disease.
The company started in 2001 as ProEthic Pharmaceuticals, Inc., and
a majority stake in the company was acquired by Kowa Company, Ltd.
in September, 2008. A privately held company, Kowa Pharmaceuticals
America focuses its efforts on the acquisition, development,
licensing and marketing of pharmaceutical products. Its lead
product, LIPOFEN® (fenofibrate capsules), is indicated as
adjunctive therapy to diet to reduce elevated triglycerides and to
increase HDL-C in adult patients with primary hypercholesterolemia
or mixed dyslipidemia. For more information about KPA, please visit
http://www.kowapharma.com/. About Lilly Lilly, a leading
innovation-driven corporation, is developing a growing portfolio of
pharmaceutical products by applying the latest research from its
own worldwide laboratories and from collaborations with eminent
scientific organizations. Headquartered in Indianapolis, Ind.,
Lilly provides answers - through medicines and information - for
some of the world's most urgent medical needs. Additional
information about Lilly is available at http://www.lilly.com/. C:
LLY This news release contains forward-looking statements. These
statements are subject to known and unknown risks and uncertainties
that may cause actual future experience and results to differ
materially from the statements made. Factors that might cause such
a difference include, among others, Lilly and Kowa' abilities to
successfully commercialize and market Livalo, competition from
other pharmaceutical companies (including generic versions of other
statin products), potential regulatory developments affecting the
product, and other factors described in Lilly's most recent filings
with the Securities and Exchange Commission. For additional
information about the factors that affect the company's business,
please see Lilly's latest Form 10-K, filed February 2009, and Form
10-Q filed October 2009. Lilly undertakes no duty to update
forward-looking statements. LIVALO® (pitavastatin, Kowa
Pharmaceuticals America Inc.) Lipitor® (atorvastatin, Pfizer Inc.)
Zocor® (simvastatin, Merck and Co., Inc) Pravachol® (pravastatin,
Bristol-Myers Squibb Company) DATASOURCE: Eli Lilly and Company
CONTACT: Mark E. Taylor, +1-317-276-5795 (Lilly); or Lauren Vinson,
+1-334-288-1288 (Kowa / Kowa Pharmaceuticals America)
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