New Superiority Trial Showed LIVALO® (pitavastatin) 4 mg Provided Significantly Greater LDL-C Reduction in HIV-Infected Adults

      New Superiority Trial Showed LIVALO® (pitavastatin) 4 mg Provided
Significantly Greater LDL-C Reduction in HIV-Infected Adults with Dyslipidemia
                           versus Pravastatin 40 mg

Study results presented as late-breaker at CROI 2013 this week

PR Newswire

ATLANTA, March 7, 2013

ATLANTA, March 7, 2013 /PRNewswire/ -- Kowa Pharmaceuticals America, Inc. and
Eli Lilly and Company (NYSE:LLY)announced results of a study evaluating the
efficacy of LIVALO^® (pitavastatin) 4 mg compared with pravastatin 40 mg in
reducing low-density lipoprotein cholesterol (LDL-C) in HIV-infected adults
with high cholesterol, or dyslipidemia. The study was designed as a
superiority trial for the primary endpoint, percent reduction in LDL-C, and
evaluated HIV-infected adults with dyslipidemia; with and without viral
Hepatitis B or C. The study met its primary endpoint.^1



Results showed that, after 12 weeks of therapy, pitavastatin had a
significantly greater decrease in LDL-C compared with pravastatin
(pitavastatin -49.4 mg/dL and pravastatin -33.6 mg/dL, 31% vs 21% reduction in
LDL-C, respectively, p<0.001). The results were presented yesterday at a
late-breaking poster presentation at the 20th Conference on Retroviruses &
Opportunistic Infections (CROI) in Atlanta, GA.^1^

Dyslipidemia is common in people with HIV infection.^2 HIV-infected adults are
at an increased risk for cardiovascular disease due to many factors, including
lipid abnormalities.^3

"We are pleased that the study objective was met, showing superiority of
pitavastatin 4 mg to pravastatin 40 mg on LDL-C reduction in HIV-infected
adults with dyslipidemia, and we look forward to further analysis of these
data," said Dr. Craig Sponseller, Vice President of Medical Affairs, Kowa
Pharmaceuticals America, Inc.

Study investigator, Dr. Judith Aberg, Director of Virology, Bellevue Hospital
Center and Director, Division of Infectious Diseases and Immunology, NYU
School of Medicine, said, "In HIV-infected patients with high cholesterol,
data such as these represent an important step in understanding lipid
management in this immunocompromised patient population."

The overall incidence of treatment emergent adverse events (TEAEs) was 61.1%
for pitavastatin and 62.7% for pravastatin. The most frequently reported TEAEs
overall (in >2% of subjects in either treatment group) included diarrhea (13
subjects, 5.2%), upper respiratory tract infection (13 subjects, 5.2%),
sinusitis (12 subjects, 4.8%), headache (10 subjects, 4.0%), nausea (10
subjects, 4.0%), nasopharyngitis (9 subjects, 3.6%), and blood creatine
phosphokinase increased (8 subjects, 3.2%). Eleven subjects were discontinued
from the study due to a TEAE (4.4%).^1

About the Study
In the 12-week, Phase 4, randomized (1:1), double-blind, double-dummy,
active-controlled, parallel-group study, 252 patients were randomized to
receive once-daily doses of pitavastatin 4 mg or pravastatin 40 mg. The
primary efficacy analysis (ANCOVA) used percent change in LDL-C as the
dependent variable, and treatment, site, and viral hepatitis B or C infection
as independent variables. The major secondary lipid endpoints assessed were
total cholesterol, HDL-C, non-HDL-C and triglycerides. Safety assessments
included adverse events, clinical/laboratory tests, HIV-1 RNA, CD4 count, and
virologic failure.^1

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 high-density lipoprotein cholesterol (HDL-C) in adult patients with
primary hyperlipidemia or mixed dyslipidemia.

Limitations of Use:

  oDoses 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.
  oThe effect of LIVALO on cardiovascular morbidity and mortality has not
    been determined.
  oLIVALO has not been studied in Fredrickson Type I, III, and V

In addition to being launched in the U.S. in June 2010, LIVALO has been
approved in Japan and 32 other countries as of January 2013.

Primary Hyperlipidemia and Mixed Dyslipidemia
Primary hyperlipidemia is defined as an elevation of cholesterol, particularly
"bad" cholesterol (LDL-C), triglycerides (TG), or both. Mixed dyslipidemia is
usually characterized by an elevation of LDL-C, TG, and a decrease in the
"good" cholesterol (HDL-C) in the blood.


LIVALO is contraindicated in patients with a known hypersensitivity to product
components, in patients with active liver disease (which may include
unexplained persistent elevations in hepatic transaminase levels), in women
who are pregnant or may become pregnant, in nursing mothers, or in
co-administration with cyclosporine.


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.

  oLIVALO should be prescribed with caution in patients with predisposing
    factors for myopathy
  oThe risk of skeletal muscle effects (e.g., myopathy, and rhabdomyolysis)
    increases in a dose-dependent manner with advanced age (>65 years), renal
    impairment, inadequately treated hypothyroidism, and in combination use
    with fibrates or lipid-modifying doses of niacin (>1 g/day)
  oLIVALO 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
  oConcomitant administration of LIVALO with gemfibrozil should be avoided
  oLIVALO therapy should be discontinued if markedly elevated 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)
  oAdvise patients to promptly report unexplained muscle pain, tenderness, or
    weakness, particularly if accompanied by malaise or fever, and to
    discontinue LIVALO if these signs or symptoms appear
  oThere have been rare reports of immune-mediated necrotizing myopathy
    (IMNM), an autoimmune myopathy, associated with statin use. IMNM is
    characterized by: proximal muscle weakness and elevated serum creatine
    kinase, which persist despite discontinuation of statin treatment; muscle
    biopsy showing necrotizing myopathy without significant inflammation;
    improvement with immunosuppressive agents. IMNM has not been reported with
    LIVALO therapy
  oAdvise patients to promptly report if muscle signs and symptoms persist
    after discontinuing LIVALO as this may be a sign of IMNM requiring
    immediate medical attention

Liver Enzyme Abnormalities
Increases in serum transaminases have been reported with HMG-CoA reductase
inhibitors, including LIVALO.

  oIt is recommended that liver enzyme tests be performed before the
    initiation of LIVALO and if signs or symptoms of liver injury occur
  oThere have been rare postmarketing reports of fatal and non-fatal hepatic
    failure in patients taking statins, including pitavastatin. If serious
    liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice
    occurs during treatment with LIVALO, promptly interrupt therapy. If an
    alternate etiology is not found do not restart LIVALO
  oAdvise patients to promptly report any symptoms that may indicate liver
    injury, including fatigue, anorexia, right upper abdominal discomfort,
    dark urine or jaundice
  oLIVALO should be used with caution in patients who consume substantial
    quantities of alcohol and/or have a history of chronic liver disease

Endocrine Function
Increases in HbA1c and fasting serum glucose levels have been reported with
HMG-CoA reductase inhibitors, including LIVALO.

In short-term controlled studies, the most frequent adverse reactions reported
by >2% of patients treated with LIVALO 1 mg, 2 mg, and 4 mg, respectively, and
at a rate> placebo were back pain (3.9%, 1.8%, 1.4% vs 2.9%), constipation
(3.6%, 1.5%, 2.2% vs 1.9%), diarrhea (2.6%, 1.5%, 1.9% vs 1.9%), myalgia
(1.9%, 2.8%, 3.1% vs 1.4%), and pain in extremity (2.3%, 0.6%, 0.9% vs 1.9%).
This is not a complete listing of all reported adverse events.

For additional information please see the full Prescribing Information
provided, or visit

LIV-RA-0058 PS82458 1/2013

About Kowa Company, Ltd. and Kowa Pharmaceuticals America, Inc.
Kowa Company, Ltd. (KCL) is a privately held multinational company
headquartered in Nagoya, Japan. Established in 1894, KCL is actively engaged
in various manufacturing and commercial activities in the fields of
pharmaceutical, life science, information technology, textiles, machinery and
various consumer products. KCL's pharmaceutical division is focused on
cardiovascular therapeutics, with sales of the company's flagship product
LIVALO, totaling $567 million in Japan in 2012, and was launched in the United
States in June 2010.

Kowa Pharmaceuticals America, Inc. (KPA) is a pharmaceutical company
specializing primarily in the area of cardiometabolic diseases. The company,
started in 2001 as ProEthic Pharmaceuticals, Inc., was acquired by KCL in
September of 2008. A privately held company, KPA directs its efforts towards
the acquisition, licensing and marketing of pharmaceutical products.

exchange rate used $1=90JPY

About Eli Lilly and Company
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

This press release contains certain forward-looking statements about LIVALO^®,
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
high-density lipoprotein cholesterol (HDL-C) in adult patients with primary
hyperlipidemia or mixed dyslipidemia. This release reflects Lilly and Kowa's
current beliefs; however, as with any pharmaceutical product, there are
substantial risks and uncertainties in the process of development and
commercialization. There is no guarantee that future study results and
patient experience will be consistent with study findings to-date or that
LIVALO will be commercially successful. For further discussion of these and
other risks, see Lilly's filings with the United States Securities and
Exchange Commission. Lilly undertakes no duty to update forward-looking

LIVALO is a registered trademark of the Kowa group of companies.


^1 Data on File: Sponseller C, Morgan R, Campbell S, et al. Pitavastatin 4 mg
Provides Greater LDL-C Reduction Compared to Pravastatin 40 mg over 12 weeks
of Treatment in HIV-infected Adults with Dyslipidemia. Poster presentedat
the 20th Conference on Retroviruses & Opportunistic Infections, March 3-6,
2013; Atlanta, GA.

^2 Boccara F. Lang S, Meuleman C, et al. HIV and Coronary Heart Disease.
Journal of the American College of Cardiology. 2013; 61(5):511-523.
< p511/1>.

^3 Malvestutto CD, Aberg JA. Management of dyslipidemia in HIV-infected
patients. Journal of Clinical Lipidology. 2011; 6(4):447-462.

SOURCE Kowa Pharmaceuticals America, Inc. and Eli Lilly and Company

Contact: Eliza Merves, Makovsky for Kowa Pharmaceuticals America, Inc., Office
+1-212-508-9631, Mobile +1-908-256-1243,; Lisa Garman,
Kowa Pharmaceuticals America, Inc., Mobile +1-404-291-4772,; or Christina Gaines, APR, Eli Lilly and Company,
Office +1-317-276-3845, Mobile +1-317-366-2568,
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