Trial shows CERVARIX cervical cancer candidate vaccine effective

Results from an interim analysis of a Phase III study show that CERVARIX, the GlaxoSmithKline (GSK) cervical cancer candidate vaccine, provides up to 100 percent protection against advanced precancerous lesions caused by the most common types of human papillomavirus, types 16 and 18.

The study also strengthens earlier preliminary evidence that the vaccine provides significant protection against infection with additional cancer-causing virus types. These results were published today in The Lancet.

"This landmark trial has provided important new insights into the natural history of cervical lesions, and helps us to more clearly understand the causal link between these lesions and the virus types detected within them," said Gary Dubin, M.D., Vice President, North American Clinical Development, GSK.

"These results validate our previous clinical findings, and we believe that the data in this study show the GSK candidate vaccine provided 100 percent protection against precancerous lesions caused by virus types 16 and 18, which are responsible for 70 percent of all cervical cancers," commented David Stout, President of Pharmaceuticals Operations, GSK.

In this study, the majority of precancerous lesions included in the primary analysis had multiple cancer-causing virus types detected, making it difficult to clearly determine which virus type was the cause of the lesion. The observation of such a high number of lesions with multiple virus types was not expected based on published data. This necessitated additional analyses to determine which virus type was the cause of the lesion. In these analyses, causality was determined by confirming the presence of the virus in both the lesion and in previous Pap smear samples.

-- When using the pre-specified analyses which only required detection of virus in the lesion, and not taking previous samples into account, vaccine efficacy in women with virus type 16 and/or 18 in the lesion was 90 percent. -- When considering the virus type present in both the lesion and previous samples, the vaccine was 100 percent effective in preventing precancerous lesions caused by virus types 16 and/or 18.

"The findings are very encouraging because the women in the study are representative of the patients seen by physicians every day in their practice," said lead investigator Professor Jorma Paavonen, Department of Obstetrics and Gynecology at Helsinki University Central Hospital, Finland. "This provides a strong indication that this vaccine can protect women from the infections that may develop into cervical cancer."

This pivotal, Phase III study involves 18,644 women aged 15 to 25 from 14 countries across Europe, Asia-Pacific and Latin and North America, making it the single largest cervical cancer vaccine efficacy trial to date.

In this clinical trial, the vaccine showed significant cross-protection against 6-month persistent infection caused by virus types 45, 31 and 52. Together with virus types 16 and 18, these types are collectively responsible for more than 80 percent of cervical cancer cases globally.

"These results suggest protection from persistent infection with additional cancer-causing virus types beyond those contained in the vaccine," said Professor Margaret Stanley, Pathology Department, University of Cambridge, UK. "This is important because persistent infection is a necessary first step in the development of precancerous lesions and cervical cancers."

The data also shows that the GSK candidate vaccine, formulated with the innovative adjuvant system AS04, produced a robust immune response for both virus types 16 and 18. This strong immune response has been shown to persist for up to 5.5 years in previous studies.

As in previous studies conducted over the past five years and involving over 40,000 women, the candidate vaccine has been shown to be generally well- tolerated.

These data are interim results from an ongoing Phase III randomized, controlled trial of 18,644 women aged between 15 to 25 from across four continents - Asia-Pacific, Europe, Latin America and North America, in a total of 14 countries.

This interim analysis shows results over an average follow-up time of 15 months after first vaccination, in which a proportion of the women enrolled already had a human papillomavirus infection or abnormal cytology (abnormal Pap smears) at study entry.

The primary objective of the interim analysis was to evaluate the vaccine efficacy against precancerous lesions associated with cancer-causing virus types 16 and 18 among women who were DNA-negative and seronegative for the corresponding vaccine type at study entry. Secondary objectives included efficacy against 6- and 12-month persistent infection with virus types 16, 18 or other cancer-causing virus types, immunogenicity and safety.

In May, CERVARIX was granted its first license in a major market by the Therapeutic Goods Administration (TGA) of Australia for the prevention of cervical cancer and precancerous lesions caused by human papillomavirus types 16 and 18 for use in females ages 10 to 45 years. This is the first time that a cervical cancer vaccine has been explicitly indicated anywhere in the world for women over the age of 26.

GSK submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its cervical cancer candidate vaccine in March 2007, following earlier regulatory filings with the European Medicines Agency (EMEA) and regulatory filings in Africa, Asia and Latin America.

Worldwide, more than 500,000 women will be newly diagnosed with cervical cancer and over 280,000 women will die from it each year. In the United States, after breast cancer, cervical cancer is the leading cause of cancer death in women ages 20-39. Cervical cancer and precancerous lesions are a major health, psychological and social burden on women everywhere.

Published data shows that any given time, only 2.3 percent of women ages 14-59 are currently infected with cancer-causing human papillomavirus types 16 and 18. Only 0.1 percent are currently infected with both types. Therefore, the vast majority of these women (up to 99.9 percent) may benefit from vaccination as they are not actively infected with these virus types and are potentially at risk for developing an infection in the future. Naturally occurring infections with cancer-causing virus types may resolve on their own, but this previous exposure may not protect against future infections with the same virus types. Some infections persist and develop into precancerous lesions, which can advance into cancer.