Phase II study of Gardasil is Published for the First Time in The Lancet Oncology -
Gardasil, the investigational vaccine against HPV from Merck & Co., Inc., significantly reduced the combined incidence of persistent HPV 6, 11, 16, or 18 infection and related diseases, including new cervical pre-cancers and genital warts compared to placebo in a Phase II study published for the first time in The Lancet Oncology.
"The level of protection in this study against infection with these four HPV types, including pre-cancerous lesions, was significant," said the study's lead investigator, Luisa Villa, PhD, head of the Virology Group at the Ludwig Institute for Cancer Research, Sao Paulo branch.
About the Study
This phase II, randomized, double-blind, placebo-controlled study evaluated the efficacy of Gardasil in preventing infection from the types of HPV responsible for 70 percent of all cases of cervical cancer and 90 percent of all cases of genital warts. In the study, 552 women in the United States, Europe and Brazil between the ages of 16 and 23 were randomized to receive vaccine or placebo at Day 1, Month 2, and Month 6. The primary endpoint of the study was to assess the efficacy of the investigational vaccine in reducing the combined incidence of persistent HPV 6, 11, 16, and 18 infections and related diseases, including cervical pre-cancers (cervical intraepithelial neoplasia, or CIN), cervical cancer, and/or external genital lesions (genital warts).
Over the two and a half years of follow-up after vaccination, Gardasil reduced the combined incidence of persistent infection from HPV 6, 11, 16, or 18 and related genital disease including new cervical pre-cancers and genital warts by 90 percent compared with placebo among women who were naive to the relevant HPV types at baseline (p<0.001). Thirty-six cases of either disease, persistent infection, or detection of HPV on the last visit on record were seen in the placebo group compared to four in the group who received Gardasil. Of the four cases seen in the group who received Gardasil, one was confirmed as persistent infection; in the other three cases HPV was detected on the last study visit but was not later confirmed as a persistent infection.
The women who participated in this study were randomized to receive either the vaccine or the placebo at day 1, month 2 and month 6. At regular intervals for 30 months following the 6-month vaccine or adjuvant-containing placebo regimen, the participating women underwent gynecologic examination and sampling to determine HPV status.
"This study evaluated the effectiveness of Gardasil in reducing the combined incidence of persistent HPV infections and related diseases, including new cervical pre-cancers and genital warts caused by HPV 6, 11, 16 and 18," said Kevin Ault, MD, Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine. "Although the study was not originally designed or powered to assess vaccine efficacy on the disease endpoints separately, efficacy of the investigational vaccine against cervical pre-cancers caused by the HPV types 16 18, 6 and 11 was 100 percent."
Adverse events related to the injection site were higher among those who received Gardasil compared with placebo recipients. The most common injection site and systemic adverse events were pain and headache, respectively. None of the subjects who received the investigational vaccine discontinued the study due to an adverse experience.
In this study, vaccination with Gardasil induced an immune response as measured by anti-HPV serum antibody titers. Anti-HPV 6, 11, 16 and 18 geometric mean titers (GMTs) at the completion of the vaccine regimen (month 7) were substantially higher among vaccinated women than among placebo-recipients with a previous history of natural HPV infection. Although antibody levels among the women vaccinated with Gardasil started to decline after month 7, at month 36 they still remained at or above those observed in women in the placebo group who had an immune response to a previous natural HPV infection.
Phase III clinical trials to evaluate Gardasil are currently underway with over 25,000 participants enrolled worldwide. Phase III data are expected to be available later this year.
Cervical Cancer, HPV and Genital Warts
It is estimated that approximately 20 million American men and women are infected with HPV. In most people, HPV appears to go away on its own. In some, the virus has been linked to cervical cancer, abnormal pap tests and genital warts. In the United States, an estimated 10,370 new cases of cervical cancer will be diagnosed in 2005, and there will be an estimated 3,710 deaths from cervical cancer. Genital warts are common - 500,000 to 1,000,000 cases in the United States alone - and treatment options may be painful.
"HPV types 6 or 11 are not linked to cervical cancer, but they can cause abnormal Pap smears, which then lead to additional tests - and unnecessary worries about cancer," said Eliav Barr, MD, senior director of Clinical Research, Merck Research Laboratories, and a co-author of the study. "Gardasil was purposefully designed to target the HPV types most commonly associated with cervical cancer, as well as the types that cause genital warts and many abnormal Pap smears, to reduce the burden from HPV infection as much as possible."
In 1995, Merck entered into a license with CSL Limited relating to technology used in Gardasil.
About Merck & Co.
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. http://www.merck.com.
Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2004, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.
Gardasil, the investigational vaccine against HPV from Merck & Co., Inc., significantly reduced the combined incidence of persistent HPV 6, 11, 16, or 18 infection and related diseases, including new cervical pre-cancers and genital warts compared to placebo in a Phase II study published for the first time in The Lancet Oncology.
"The level of protection in this study against infection with these four HPV types, including pre-cancerous lesions, was significant," said the study's lead investigator, Luisa Villa, PhD, head of the Virology Group at the Ludwig Institute for Cancer Research, Sao Paulo branch.
About the Study
This phase II, randomized, double-blind, placebo-controlled study evaluated the efficacy of Gardasil in preventing infection from the types of HPV responsible for 70 percent of all cases of cervical cancer and 90 percent of all cases of genital warts. In the study, 552 women in the United States, Europe and Brazil between the ages of 16 and 23 were randomized to receive vaccine or placebo at Day 1, Month 2, and Month 6. The primary endpoint of the study was to assess the efficacy of the investigational vaccine in reducing the combined incidence of persistent HPV 6, 11, 16, and 18 infections and related diseases, including cervical pre-cancers (cervical intraepithelial neoplasia, or CIN), cervical cancer, and/or external genital lesions (genital warts).
Over the two and a half years of follow-up after vaccination, Gardasil reduced the combined incidence of persistent infection from HPV 6, 11, 16, or 18 and related genital disease including new cervical pre-cancers and genital warts by 90 percent compared with placebo among women who were naive to the relevant HPV types at baseline (p<0.001). Thirty-six cases of either disease, persistent infection, or detection of HPV on the last visit on record were seen in the placebo group compared to four in the group who received Gardasil. Of the four cases seen in the group who received Gardasil, one was confirmed as persistent infection; in the other three cases HPV was detected on the last study visit but was not later confirmed as a persistent infection.
The women who participated in this study were randomized to receive either the vaccine or the placebo at day 1, month 2 and month 6. At regular intervals for 30 months following the 6-month vaccine or adjuvant-containing placebo regimen, the participating women underwent gynecologic examination and sampling to determine HPV status.
"This study evaluated the effectiveness of Gardasil in reducing the combined incidence of persistent HPV infections and related diseases, including new cervical pre-cancers and genital warts caused by HPV 6, 11, 16 and 18," said Kevin Ault, MD, Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine. "Although the study was not originally designed or powered to assess vaccine efficacy on the disease endpoints separately, efficacy of the investigational vaccine against cervical pre-cancers caused by the HPV types 16 18, 6 and 11 was 100 percent."
Adverse events related to the injection site were higher among those who received Gardasil compared with placebo recipients. The most common injection site and systemic adverse events were pain and headache, respectively. None of the subjects who received the investigational vaccine discontinued the study due to an adverse experience.
In this study, vaccination with Gardasil induced an immune response as measured by anti-HPV serum antibody titers. Anti-HPV 6, 11, 16 and 18 geometric mean titers (GMTs) at the completion of the vaccine regimen (month 7) were substantially higher among vaccinated women than among placebo-recipients with a previous history of natural HPV infection. Although antibody levels among the women vaccinated with Gardasil started to decline after month 7, at month 36 they still remained at or above those observed in women in the placebo group who had an immune response to a previous natural HPV infection.
Phase III clinical trials to evaluate Gardasil are currently underway with over 25,000 participants enrolled worldwide. Phase III data are expected to be available later this year.
Cervical Cancer, HPV and Genital Warts
It is estimated that approximately 20 million American men and women are infected with HPV. In most people, HPV appears to go away on its own. In some, the virus has been linked to cervical cancer, abnormal pap tests and genital warts. In the United States, an estimated 10,370 new cases of cervical cancer will be diagnosed in 2005, and there will be an estimated 3,710 deaths from cervical cancer. Genital warts are common - 500,000 to 1,000,000 cases in the United States alone - and treatment options may be painful.
"HPV types 6 or 11 are not linked to cervical cancer, but they can cause abnormal Pap smears, which then lead to additional tests - and unnecessary worries about cancer," said Eliav Barr, MD, senior director of Clinical Research, Merck Research Laboratories, and a co-author of the study. "Gardasil was purposefully designed to target the HPV types most commonly associated with cervical cancer, as well as the types that cause genital warts and many abnormal Pap smears, to reduce the burden from HPV infection as much as possible."
In 1995, Merck entered into a license with CSL Limited relating to technology used in Gardasil.
About Merck & Co.
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. http://www.merck.com.
Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2004, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.
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