Merck filed an sBLA seeking expanded indications for the human papilloma virus vaccine Gardasil for protection against vaginal and vulvar cancers. The firm announced the submission April 17.

Currently the only HPV vaccine approved in the U.S., Gardasil is indicated for vaccination of women and girls ages nine to 26 to prevent cervical cancer, cervical pre-cancers, vulvar pre-cancers and vaginal pre-cancers caused by HPV types 16 and 18, as well as genital warts and low-grade cervical lesions caused by HPV types 6, 11, 16 and 18. It was approved in June (¹ Also see "Merck’s Gardasil HPV Vaccine Clears FDA" - Pink Sheet, 8 June, 2006.).

The recent FDA submission includes "efficacy data showing some protection against additional cervical cancer-causing HPV types responsible for greater than 10 percent of cervical cancers, data on protection against additional gynecological cancers ... and data on immune memory," Merck said.

The data stems from two Phase III clinical trials, FUTURE 1 and FUTURE 2, the company said. Merck began vaccinations of the placebo arms of those trials in February after a data safety monitoring board found highly positive efficacy results.

GlaxoSmithKline, meanwhile, is seeking approval of its own HPV vaccine candidate, Cervarix ; the company submitted a BLA for the product in March seeking a priority review (² Also see "GlaxoSmithKline Submits Cervarix BLA" - Pink Sheet, 29 March, 2007.).

During the American Association for Cancer Research annual meeting in Los Angeles April 17, GSK released additional clinical trial data on Cervarix, demonstrating 100 percent efficacy in preventing precancerous lesions due to cancer-causing HPV types 16 and 18 for up to 5.5 years in an extended follow-up trial.

The vaccine candidate also showed 68 percent efficacy against precancerous lesions and 38 percent efficacy against abnormal Pap smears, regardless of the type of cancer-causing virus detected, GSK said.

The results suggest protection "beyond what might be expected from a vaccine that is designed to target" HPV 16 and 18 alone, offering evidence that Cervarix provides "cross-protection against incident infection with cancer-causing virus types 45 and 31 that also extended up to 5.5 years," the company said.

Additionally, Cervarix "induced a strong immune response in virtually 100 percent of women in the study," with antibody levels at least 11 times greater than those associated with natural infection with the virus, GSK said.

GSK is seeking to position Cervarix as superior to Gardasil because of its proprietary adjuvant system and launched a head-to-head trial comparing the vaccines in January (³ Also see "GSK Wagers On Cervarix In Head-To-Head Trial Against Gardasil" - Pink Sheet, 18 January, 2007.).

Roche and Transgene also announced earlier this month that they would collaborate on development of a therapeutic vaccine to treat HPV-mediated diseases (⁴ Also see "Roche And Transgene Partner On Therapeutic Vaccine For HPV-Related Diseases" - Pink Sheet, 12 April, 2007.).

Even with Merck and potentially GSK marketing prophylactic vaccines, "you're still going to need something for treatment as opposed to prevention," Roche told "The Pink Sheet" DAILY. "You're never 100 percent certain that everyone might get a vaccine."

A challenge for Merck has been finding girls and women not already infected with one or all of the four virus types on which to test Gardasil. In clinical trials, vaccinated women were not followed for virus types for which they already tested positive.

Prescribing information for Gardasil notes that 27 percent of individuals who entered clinical trials for the vaccine "had evidence of prior exposure to or ongoing infection with at least one of the four HPV types" and that "there was no clear protection from disease caused by HPV types for which subjects were ... positive at baseline."

The trial population was representative of the general population of American women, Merck said.

- Shirley Haley (s.haley@elsevier.com)

Merck Seeks Additional Claims For Gardasil

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