New Data Showed Minimal Potential for Drug Interaction Between Cholesterol Drug LIVALO and a Common Antiretroviral Therapy

MONTGOMERY, Ala. and INDIANAPOLIS, July 18, 2011 /PRNewswire/ –Kowa
Pharmaceuticals America, Inc. and Eli Lilly and Company (NYSE: LLY) today
released new study results that investigated the potential interaction of
cholesterol drug LIVALO (pitavastatin) 4 mg in healthy volunteers taking the
protease inhibitor (PI) combination lopinavir/ritonavir, a fixed dose
combination drug for the treatment of HIV infection.(1) Protease inhibitors are
commonly used antiretroviral HIV medications.(2) The study, presented at the 6th
International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and
Prevention in Rome, Italy, found that when co-administered, the individual drug
blood levels for LIVALO or each of the PIs was minimally affected. Based on
these data from this FDA-mandated phase IV study, the United States Food and
Drug Administration recently approved a labeling change to delete the
lopinavir/ritonavir limitation of use from the U.S. LIVALO labeling.

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“HIV is a chronic illness today, as opposed to 30 years ago, and patients with
HIV are faced with additional challenges concerning dyslipidemia, accentuated by
both the disease process as well as antiretroviral therapies. Additionally,
these patients are frequently on multiple medications and the management of
dyslipidemia can be even more of a challenge. We are pleased with the results of
this study and the absence of a significant drug interaction when LIVALO is
co-administered with this combination of protease inhibitors,” said Craig
Sponseller, MD, Vice President of Medical Affairs, Kowa Pharmaceuticals America,
Inc.

The study was designed to assess the pharmacokinetic (PK) interaction, or effect
on overall exposure in the body, of the combination lopinavir/ritonavir on the
PK of LIVALO, and secondarily any potential PK effect of LIVALO on lopinavir and
ritonavir.(3) LIVALO (4 mg) and lopinavir/ritonavir (800 mg/200 mg) were
co-administered in 24 healthy, adult volunteers over a 24 day period. At study
end, peak exposure of pitavastatin at steady state, as measured by C(max), was
not affected by co-administration of lopinavir/ritonavir. Total exposure of
pitavastatin at steady state, as measured by AUC(0-T), was weakly affected by
co-administration of lopinavir/ritonavir (decrease of approximately 20%). C(max)
and AUC(0-T) of lopinavir and ritonavir at steady state were marginally affected
by co-administration of pitavastatin. These effects were not considered to be
clinically significant.(4)

A second objective of the study was to investigate any potential effect on the
safety of LIVALO by the addition of lopinavir/ritonavir. No significant safety
issues were observed. Eighteen of 24 patients reported at least one treatment
emergent adverse event (TEAE), with the highest percentage coming from subjects
receiving lopinavir/ritonavir only. All TEAEs were mild in severity, except for
four subjects who had TEAEs after lopinavir/ritonavir only that were moderate in
severity. One subject was discontinued from the study because of an adverse
event (AE) of diarrhea during treatment with lopinavir/ritonavir only. There
were no severe AEs, SAEs, or deaths.(5)

“This study is important to caregivers and patients alike, as LIVALO showed
minimal drug-drug interactions with a common antiretroviral therapy HIV patients
need to fight the disease. For a patient population that is taking multiple
medications, this is exciting news,” said Dr. Judith Aberg, Director of
Virology, Bellevue Hospital Center and Director, Division of Infectious Diseases
and Immunology, NYU School of Medicine.

Elevated cholesterol, particularly the “bad” cholesterol, low density
lipoprotein cholesterol (LDL-C), triglycerides (TG), or both, is a common
complication associated with HIV infection as well as the use of antiretroviral
therapies.(6,7) The frequency of hyperlipidemia, elevation of fats in the blood,
in HIV-infected patients taking protease inhibitors, including
lopinavir/ritonavir, is up to 66 percent of the patient population.(8)

Cholesterol-lowering drugs, particularly statins, are often used in patients
with HIV; therefore it is important for physicians to understand the potential
drug-drug interactions with antiretroviral therapies.

About LIVALO

LIVALO is a HMG-CoA reductase inhibitor indicated for patients with primary
hyperlipidemia and mixed dyslipidemia 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). LIVALO is predominantly metabolized via
glucuronidation and is only minimally metabolized by CYP system, which may help
reduce its potential for CYP-mediated drug-drug interactions.

In addition to being launched in the U.S. June 2010, LIVALO is also approved in
Japan (2003), South Korea (2005), Thailand (2007), China (2008), European Union
(2010), Taiwan (2011) and Lebanon (2011).

About 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.

Despite the availability of treatments in the U.S. there is still a need for
more options to help treat elevated cholesterol. According to the American Heart
Association, approximately one out of every three American adults has an LDL-C
level of 130 mg/dL or higher, which is a major health risk. In addition, less
than half of patients who qualify for any kind of lipid-modifying treatment are
receiving it, and only about one-third of patients who are on treatment are
achieving their LDL-C goals.

What is LIVALO?

LIVALO is a prescription medicine that, along with diet, has been approved for
the treatment of high cholesterol.

LIVALO has not been studied to evaluate its effect on reducing heart-related
disease or death.

LIVALO Important Safety Information

Who should NOT take LIVALO?

LIVALO is not right for everyone, including:

— Those who have had an allergic reaction to LIVALO
— Anyone with liver disease
— Patients with severe kidney disease not on hemodialysis
— Women who are nursing, pregnant, or who may become pregnant
— Anyone currently taking cyclosporine
What should I talk to my doctor about?

— If you take LIVALO, tell your doctor right away if you experience any
unexplained muscle pain, tenderness, or weakness, particularly if
accompanied by fever or a general feeling of discomfort. This could be a
sign of a rare but serious side effect.
— Your doctor should do blood tests to monitor your liver function before
starting LIVALO, and then at 12 weeks following the start of LIVALO,
after any increase in dose, and periodically (e.g., every 6 months)
thereafter.
— Please talk to your doctor about your alcohol use.
— Tell your doctor about all the medications you take including
nonprescription medicines, vitamins, or herbal supplements.
What are the most common side effects of LIVALO?

The most common side effects of LIVALO in clinical studies were:

— Back pain
— Constipation
— Diarrhea
— Muscle pain
— Pain in the legs or arms
This is not a complete list of side effects.

For more information about LIVALO, and to access the Full Prescribing
Information go to www.LIVALORX.com.

(1) Sponseller, C. Effects of Steady State Lopinavir/Ritonavir on the
Pharmacokinetics of Pitavastatin in Healthy Adult Volunteers. 6th International
AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.
Rome, Italy. July 17-20, 2011.

(2) Sponseller, C. Effects of Steady State Lopinavir/Ritonavir on the
Pharmacokinetics of Pitavastatin in Healthy Adult Volunteers. 6th International
AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.
Rome, Italy. July 17-20, 2011.

(3) Sponseller, C. Effects of Steady State Lopinavir/Ritonavir on the
Pharmacokinetics of Pitavastatin in Healthy Adult Volunteers. 6th International
AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.
Rome, Italy. July 17-20, 2011.

(4) Sponseller, C. Effects of Steady State Lopinavir/Ritonavir on the
Pharmacokinetics of Pitavastatin in Healthy Adult Volunteers. 6th International
AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.
Rome, Italy. July 17-20, 2011.

(5) Sponseller, C. Effects of Steady State Lopinavir/Ritonavir on the
Pharmacokinetics of Pitavastatin in Healthy Adult Volunteers. 6th International
AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.
Rome, Italy. July 17-20, 2011.

(6) Calza L, Manfredi R, Pocaterra D, Chiodo F. Risk of premature
atherosclerosis and ischemic heart disease associated with HIV infection and
antiretroviral therapy. J Infect 2008; 57:16-32.

(7) Echevarria KL, Hardin TC, Smith JA. Hyperlipidemia associated with protease
inhibitor therapy. Ann Pharmacother. 1999; 33:859-63.

(8) Kaul DR, Cinti SK, Carver PL et al. HIV protease inhibitors: advances in
therapy and adverse reactions, including metabolic complications.
Pharmacotherapy. 1999; 19:281-98.

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 $530
million (14.6% market share) in Japan in the 2010 fiscal year, 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=85JPY

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 www.lilly.com. P-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 is a registered trademark of the Kowa group of companies.

PS72893 LIV-MT-124

SOURCE Kowa Pharmaceuticals America, Inc.