Shionogi USA in the News
July 10, 2002
Shionogi & Co., Ltd.
GlaxoSmithKline plc

Results of first human trial of a new class of anti-HIV drugs reported by Shionogi-GlaxoSmithKline Pharmaceuticals, LLC
Barcelona, Spain, July 9, 2002 -- Results were presented today at the XIV International Conference on Aids from the first human study of a new class of potent anti-HIV agents that target integrase. Integrase, reverse transcriptase and protease are the three enzymes necessary for viral replication. Integrase is the only viral target unaffected by currently available HIV therapies.

The compound S-1360 is being developed by Shionogi-GlaxoSmithKline Pharmaceuticals, LLC; a joint venture between companies. It is the first potential drug in this class to progress to this stage of development.

The study, a randomized, double-blind, placebo-controlled trial, was conducted in 24 healthy HIV-negative volunteers. Subjects were randomized to S-1360 500mg, 100mg, or 2000mg twice a day, or placebo. Results showed that S-1360 was generally well tolerated and showed acceptable pharmacokinetic profiles. These data support proceeding to clinical studies in HIV-positive individuals. Phase II clinical trials are currently underway.

There were no serious adverse events reported in this study. During the trial, a similar percent of subjects receiving S-1360 and placebo experienced mild to moderate adverse events (56% vs. 50%). The most frequent adverse event reported was headache.

“Progressing research on integrase inhibitors is an important step forward for AIDS research. Like reverse transcriptase and protease, integrase is essential for the virus to infect cells and replicate. Inhibiting integrase could be a new way to suppress the virus and extend treatment options for patients,” said Dr. Tamio Fujiwara, General Manager, Antiviral Research Program, Shionogi Institute for Medical Science.

Shionogi-GlaxoSmithKline Pharmaceuticals, LLC, a joint-venture created in 2001 between Shionogi & Co., Ltd., and GlaxoSmithKline Pharmaceuticals is currently developing S-1360 as well as compounds that target disorders of the central nervous system.

Shionogi & Co., Ltd., the discoverer of S-1360, is one of Japan’s largest research-based pharmaceutical companies. It develops, manufactures, distributes, imports, and exports pharmaceuticals and diagnostics. Shionogi aims to provide innovative medicines that make a positive contribution to health worldwide.

GlaxoSmithKline, the leader in HIV research, has led the development of treatments for HIV, beginning 15 years ago with the availability of Retrovir® (zidovudine), the first therapy to treat HIV. Other anti-HIV products include Epivir® (lamivudine) also known as 3TC®, Ziagen® (abacavir sulfate), and Agenerase® (amprenavir). In 1997, the company greatly simplified treatment regimins by developing Combivir® (lamivudine/zidovudine), which contains two therapies in one pill. In 2000, the first triple combination product in one pill called Trizivir® (abacavir sulfate/lamivudine/zidovudine) was approved.

Epivir, Retrovir, Combivir, Ziagen, Agenerase, and Trizivir are trademarks of the GlaxoSmithKline Group of companies.

Note to editors
Ziagen was discovered and is being developed by GlaxoSmithKline. The rights to related compounds and technology, including intermediates used in the manufacture of Ziagen, resulting from the research by Dr. Robert Vince, et al, were licensed to Glaxo Wellcome by the University of Minnesota in 1992.

Epivir was discovered by Shire Pharmaceuticals Group plc, of Basingstoke, UK and licensed to Glaxo Wellcome in 1990.

Aprenavir was disovered by scientists at Vertex Pharmaceuticals of Cambridge, MA and licensed to Glaxo Wellcome in the United States, Europe and other countries. GlaxoSmithKline has been responsible for product formulation and manufacture of Agenerase, design and implementation of clinical trials, and regulatory submissions.