Merck's presentation of data on the use of Gardasil in males at FDA's recent Vaccines & Related Biological Products Advisory Committee meeting suggests the firm is positioning the product for a broader recommendation from the Centers for Disease Control & Prevention's Advisory Committee on Immunization Practices.

While the committee was not asked to comment on vaccination of males at its May 18 meeting, the sponsor urged inclusion of males in labeling for the human papilloma virus vaccine.

"We would like to propose labeling that would allow flexibility in decision making for groups that are going to make vaccination policy in this country to evaluate whether gender-neutral vaccination should be used or female-only vaccination based on their review of the data," Merck Senior Director-Vaccines/Biologics Clinical Research Eliav Barr said.

"Our proposal is that we would provide all the information that we have generated to date, the efficacy finding of diseases in which efficacy was shown and, of course, inclusion of all immunogenicity safety data in girls, women and boys," Barr said.

ACIP, which will be reviewing the quadrivalent vaccine (HPV serotypes 6,11,16 and 18) June 29, rarely makes recommendations that fall outside the confines of FDA labeling.

During the advisory committee meeting, FDA suggested, however, that it is unlikely a male vaccination claim would be included in the label without further safety and efficacy data.

"We have no efficacy data right now in males. An extension to males will be considered when we have that data available," FDA Office of Vaccine Research & Review Reviewer Nancy Miller said.

"We don't really have any safety data in males right now over the age of...15," she added.

Although the company does not have male efficacy data, Merck asked the committee to consider the similarity of the disease in men and women and noted that clinical studies of nine- to 15-year-old boys have shown that the "safety profile is favorable."

"We know that genital warts in men and women have comparable histology, comparable natural history, the disease is impacting very [similar] cells in both instances....The skin is the same," Barr explained.

Committee industry representative Samuel Maldonado (Wyeth) agreed with Merck, asking, "[is there] any biological plausibility that the vaccine would not be efficacious or safe in males?"

"The point that we're making is that efficacy is already [proven in women] and it's highly likely to be significant [for men]," Barr stated.

A trial to confirm efficacy in males 15 to 26 years of age is underway with data expected in 2008 and inclusion in labeling by 2009.

"That means that there will be at least a three-year gap between the vaccine becoming available right now to having these data," Maldonado noted.

"By delaying for three plus years vaccination in boys, we could...have an additional 100,000 [cervical intraepithelial neoplasia] 2/3 cases that could have otherwise been avoided," Barr asserted.

"By the time uptake becomes more reasonable we're going to be way close to the end of the clinical trial [in males]. The impact will simply be on whether or not you're going to maximally start the trend toward reducing cervical cancer into the population by vaccinating boys and girls," he said.

Merck positioned male vaccination as necessary from a public health standpoint due to the indirect prevention of cervical cancer in women.

"We are interested in facilitating the possibility of public health authorities considering vaccinations of males...there is a strong public health rationale for vaccinating boys and the cost of delaying the vaccination of boys," Barr said.

In addition to cervical cancer in women, data suggests HPV is related to cancers of the anal canal, penis, larynx, oral cavity and oropharynx in men, Merck said. Furthermore, vaccine-related HPV types 6 and 11, not included in GlaxoSmithKline's investigational HPV vaccine Cervarix , account for 90% of genital warts cases.

By vaccinating men, "we will protect those men against infection, genital lesions, [and] we will prevent the cancers that we know [spread] through HPV in men," Merck consultant Myron Levin (University of Colorado) said.

"Beyond that benefit there will actually be a significant cost saving in terms of preventing all those infections in men and that in turn will impact on the cost-benefit analysis of this vaccine," he said.

However, it may be more difficult for Merck to secure a recommendation in males due to the potential for substantially higher costs of such a program, especially if the majority of savings are associated with preventing cervical disease.

"The potential for using this vaccine in males is very exciting," committee consultant Lauri Markowitz (CDC), who will preside over the ACIP meeting, said. "But I don't think we should do this right now in terms of modeling data, to make this decision."

Merck has previously indicated it is pursuing a universal coverage recommendation for routine vaccination of adolescent females, required dosing for school admittance and a catch-up program for older women (¹ Also see "Merck Initiates Gardasil Detailing; Campaign To Focus On Cancer Prevention" - Pink Sheet, 2 January, 2006., p. 6).

Breadth of ACIP recommendations generally rest on the available safety and efficacy data, cost-effectiveness modeling and manufacturing capacity.

In February, an ACIP workgroup supported a narrow HPV recommendation - routine vaccination of girls ages 11 to 12 - citing concerns over supply (² Also see "HPV Vaccines Receive Narrow Age-Range Endorsement From ACIP Workgroup" - Pink Sheet, 6 March, 2006., p. 15).

Merck has previously said it is prepared to meet demand for the vaccine upon approval.

The company is seeking an indication for ages nine to 45 for prevention of cancer, precancerous or dysplastic lesions, genital warts and infection caused by the vaccine-related HPV types.

The committee voted unanimously in support of Gardasil's efficacy and safety in females ages nine to 26; the vaccine has a June 8 user fee action date (³ Also see "Gardasil Sails Through Committee; Discussions Center On Labeling Language" - Pink Sheet, 22 May, 2006., p. 3).

Merck Seeks Early Gardasil Male Recommendation, But FDA, CDC Are Wary

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