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Merck's HPV Vaccine Gardasil Demonstrates Efficacy In Males In Late-stage Study
Thursday, Merck & Co. Inc. (MRK: News ) announced that its cervical cancer vaccine, Gardasil demonstrated efficacy in preventing HPV (human papillomavirus)-related disease in males in a late-stage study.
In the phase III study, Gardasil was 90.4 percent effective at reducing external genital lesions caused by human papillomavirus (HPV) types 6, 11, 16 and 18 in men aged 16 to 26. These are the only data evaluating efficacy of any HPV vaccine in preventing disease in males.
The company presented the placebo controlled phase III study at the European Research Organization on Genital Infection and Neoplasia or EUROGIN International Multidisciplinary Conference.
Merck said it remains on track to submit a supplemental Biologics License Application for GARDASIL to the U.S. Food and Drug Administration by the end of 2008 for the use of GARDASIL in boys and men ages 9 to 26 for the prevention of external genital lesions caused by HPV types 6, 11, 16 and 18. No vaccine-related serious adverse events were reported in this study.
The study evaluated about 3,400 heterosexual males 16 through 23 years of age and approximately 600 men 16 to 26 years of age who have sex with men. Merck noted that the study is ongoing, and additional data will be submitted to global regulatory agencies once available.
According to the company, in the late-stage study, Gardasil also achieved statistical significance on both secondary endpoints - namely 85.6 percent effective at reducing persistent infection* and 44.7 percent effective at reducing "anytime" HPV DNA detection*
*Persistent infection is when the same HPV type is detected through swabs or biopsies over two or more consecutive visits six months apart.
*Anytime HPV DNA detection means HPV DNA is found through swabs or biopsies at any visit; persistent infection is a part of "anytime" HPV DNA detection.
Gardasil was approved by the FDA in 2006 for use in females 9-26 years of age to prevent cervical cancer, precancerous genital lesions and genital warts due to HPV (human papillomavirus) types 6, 11, 16 and 18. About 70% of cervical cancers and 90% of genital warts are caused by the above-mentioned four HPV types.
Sales growth of Merck's Gardasil vaccine appears to have hit the wall. Last year, Gardasil notched up $1.5 billion in sales. For the third quarter of 2008, total Gardasil sales fell 4% to $401 million, while sales of the vaccine in the U.S. tumbled 16% to $276 million.
In June, the FDA turned thumbs down on Merck's request for approval of Gardasil for women between ages 27 and 45, citing that there are issues that preclude approval of the supplement within the expected review timeframe.
Gardasil is recommended as a three-dose regimen and each dose costs about $120. An editorial in the August 21 issue of the New England Journal of Medicine raises questions not only on the overall effectiveness of Gardasil in the protection against cervical cancer, but also on the vaccine's cost-effectiveness, compared to regular and consistent screening such as Pap smears.
The vaccine's potential side effects have also been gracing the headlines for quite sometime. As of June 30, 9,749 cases of "adverse events" associated with Gardasil administration were reported, of which 94% were deemed non serious and 6% deemed as serious. The nonserious events included injection site pain, headache, nausea, fever and fainting. The serious adverse events included 20 deaths. Other adverse side effects included blood clots and several cases of Guillain-Barre syndrome, an autoimmune disease that can lead to paralysis.
However, last month, the CDC (Centers for Disease Control and Prevention) and the FDA determined that the HPV vaccine is safe to use and effective, based on the available information. The FDA also concluded that there is no evidence that Gardasil caused the deaths or led to Guillain-Barre. But some physicians are still skeptical about the vaccine's safety.
Amid a swirl of controversy over the vaccine's safety and efficacy, and regulatory setback, Merck pared its 2008 full-year sales forecast for Gardasil to $1.4 billion - $1.6 billion from its initial estimate of $1.9 billion - $2.1 billion.
Merck said it remains on track to submit a supplemental Biologics License Application for Gardasil to the FDA by the end of 2008 for the use of the vaccine in boys and men ages 9 to 26 for the prevention of external genital lesions caused by HPV types 6, 11, 16 and 18. Other regulatory submissions around the world will occur as planned.
In September, the FDA expanded the usage of Gardasil vaccine to treat cancers of the vagina and vulva, which affect more than 5,000 women in the U.S. each year. Expanding the vaccine's indication is one sure-fire way to increase sales. Merck may see an uptick in Gardasil sales as the vaccine gets approved for new indications.
Merck Cancer Shot Cuts Genital Warts, Lesions in Men (Update2)
By Michelle Fay Cortez and Shannon Pettypiece
Nov. 13 (Bloomberg) -- Merck & Co.'s Gardasil shot, used to prevent cervical cancer in women, slashed the risk of genital warts and pre-cancerous lesions by 90 percent in men, according to the largest study of the vaccine in males.
Merck said it will use the data to seek U.S. approval to sell Gardasil for males this year to protect against warts and the lesions, which may lead to cancer of the penis and anus. The shot protects against the sexually transmitted human papillomavirus, or HPV.
Gardasil, approved for females ages 9 to 26, is given mostly to school-age girls as a U.S.-recommended routine vaccination. The vaccine is designed to prevent HPV infection, which causes cervical cancer and genital warts, and has been linked to cancers of the penis and anus in men. Expanding the vaccine to males could revive sales, which declined 4 percent in the third quarter, analysts said.
``We finally have something we may be able to offer men as well as women,'' said Anna Giuliano, professor of medicine and epidemiology at the University of South Florida and a program leader in risk assessment at the H. Lee Moffitt Cancer Center in Tampa, Florida. ``It really opens the door to preventing infection and hopefully cancer and genital warts in males.''
The research, funded by Whitehouse Station, New Jersey-based Merck, is being presented today at the European Research Organization on Genital Infection and Neoplasia in Nice, France. Merck rose $1.81, or 6.8 percent, to $28.53 at 4:04 p.m. in New York Stock Exchange composite trading.
Study Findings
Researchers gave 4,065 males ages 16 to 26 three shots of the vaccine or a placebo, then tracked them for signs of infection with HPV. After about 30 months, three men getting Gardasil developed genital warts and none had pre-cancerous growths linked to the HPV virus, compared with 28 cases of warts and three pre-cancerous lesions in the placebo group.
HPV may cause about 1,500 men to develop penile cancer a year and 1,900 to get anal cancer, according to the Centers for Disease Control and Prevention. Men who have sex with men are 17 times more likely to develop anal cancer from HPV, the CDC said.
None of the men were infected with HPV before the start of the study. The vast majority of those in the trial, 3,400 volunteers, were heterosexual males. Men are viewed as the key transmitters of HPV to women. Another 600 were homosexual men, who have an elevated risk of developing some cancers.
The shot also reduced the likelihood that the men would develop persistent HPV infection, when the virus is detected in two or more consecutive doctor visits.
Expanded Use
Expanded use of Gardasil to men and boys can help revive sales, which fell 4 percent to $401 million in the third quarter. About 2.5 million girls ages 13 to 17 were vaccinated with Gardasil last year, according to CDC. The company has been less successful in persuading young women to get the shot, which has limited sales of the product.
If approved for males, more than 350,000 boys and young men, ages 11 to 26, could get the $400 vaccine next year, increasing to more than 1 million annually by 2011, Merrill Lynch analyst David Risinger estimated in a Sept. 4 research report. He expects the vaccine could reach $2.7 billion in peak sales in 2011.
The shot protects against infection caused by HPV types 6, 11, 16 and 18 -- four of the 40 types of the virus found in the genital area. More than 1 million cases of genital lesions, which can lead to cancer, occur in men and women in the U.S. each year, and 30 million cases occur worldwide, Merck said in a statement.
While 20 million Americans are infected with HPV, most will be able to fight off the infection naturally. About 1 percent of sexually active men in the U.S. will develop genital warts from HPV, the CDC said. Gardasil is already approved for males in 40 countries worldwide.
Awaiting Data
It's unlikely that U.S. doctors will start to give the shot to boys at this stage, since the Food and Drug Administration hasn't reviewed the findings and more data is coming, Giuliano said.
``The first really important step is to have Merck do a filing with the FDA, and have the FDA make a decision,'' she said. ``Although I think you get sporadic use of vaccines off label, I don't think it would ever be common practice.''
The CDC's vaccine committee will meet next year to consider whether the shot should be recommended for boys, Giuliano said.
Merck also is awaiting an FDA decision about whether the company can market the vaccine for women through age 45.
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