by ecancer reporter Clare Sansom

The prophylactic HPV vaccine Gardasil is known to be able to prevent infection by four types of human papilloma virus, HPV 16, 18, 6 and 11, and to be effective in preventing cervical cancer and genital warts. An advisory panel of the US Food and Drug Administration has now concluded that there is strong enough evidence to support its also being licensed for the prevention of anal cancer.

Anal cancer is a relatively rare disease, although its incidence is increasing. In the US, cases doubled from 0.8 to 1.6 per 100,000 between 1975 and 2007. Although women are slightly more susceptible as a whole, men who are HIV positive or who practice receptive anal intercourse are at particularly high risk. About 90% of anal cancers are associated with HPV infection, most often with HPV 16; vaccination against HPV should therefore provide immunity to this cancer if it is given before infection occurs.

The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the FDA has based its recommendation to approve Gardasil for anal cancer on the report of a Phase III clinical trial sponsored by Merck, which developed the vaccine, and presented by clinical reviewer Jeffrey Roberts. This trial recruited 4065 HPV-negative young male subjects (16-25 years of age), including 605 who had sex with men, to receive three doses of either Gardasil or an aluminum adjuvant-containing saline (AAHS) control. The subjects were followed up at intervals for three years for HPV immunogenicity analysis, safety reports, and, where applicable, cytological analysis of anal lesions.

The primary endpoint of the study was the development of the pre-cancerous condition anal intraepithelial neoplasia (AIN) associated with infection by one of the HPV subtypes 16, 18, 6 and 11; the secondary endpoint was persistent anal infection with any anal disease.  The results showed that, within a 95% confidence limit, the vaccine prevented any grade of AIN in 78% of cases and advanced neoplasia in 75% of cases. No cases of full anal cancer were observed during the study.

The report to the FDA combined the excellent results from this efficacy study with data from previous evaluations of Gardasil for different indications. These results indicated that the vaccine had an excellent safety profile and that antibody responses in adolescent girls and boys from 9-16 were as good as those in young adults; no new additional safety data or data from adolescents was include. Together, the results presented were strong enough for the committee to recommend approval of Gardasil for prevention of anal cancer linked to HPV types 16, 18, 6 and 11 in males and females from nine to 25 years of age, although further efficacy data in female subjects was requested.

Although the FDA is not obliged to accept the recommendations of its advisory panels, this is extremely likely. If – or, more likely, when – this recommendation is approved, the addition of a further indication is likely to give Merck’s vaccine a competitive edge over the GlaxoSmithKline HPV vaccine, Cervarix.

Reference

Anal cancer indication for Gardasil. Briefing Document for the Vaccines and Related Biological Products Advisory Committee (VRBPAC) (Nov 17, 2010). Available online at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM231483.pdf