As GlaxoSmithKline gets ready for a review of Cervarix by advisors to the US Food and Drug Administration, agency staff have said the cervical cancer vaccine has a favourable risk/benefit profile.

In a memo posted on the FDA’s website, staffers noted, ahead of a Vaccines and Related Biological Products Advisory Committee meeting on Wednesday, that the jab “is expected to provide a significant public health benefit to girls and women between the ages of 10 and 25 years”. GSK is looking for approval of Cervarix to prevent cervical cancer caused by human papillomavirus types 16 and 18 in that age group.

The pathway to approval in the USA has not always been a smooth one for Cervarix, which is approved in 97 countries including the European Union states. At the end of 2007, the FDA issued GSK with a complete response letter asking for more data, which GSK provided, plus final data from a Phase III, 18,600-patient trial called HPV-008.

The staffers note that the “substantial database” contains information on 57,323 females aged 10 and above with a total follow-up of 129,454 person-years and a maximum individual follow-up of 7.4 years. Approximately seven million doses of Cervarix have been distributed (up to May, 2009) and “no safety concerns have been detected in post-marketing surveillance.

Importantly, the FDA memo notes that a large meta-analysis of potential autoimmune events in more than 68,000 subjects from studies of AS04-adjuvanted vaccines like Cervarix, demonstrated comparable event rates in vaccinees and controls “with no significant increase in relative risk”. Further analyses reviewed by external expert panels of neurologists and rheumatologists "concluded that there was no increased risk of neuroinflammatory or musculoskeletal autoimmune disorders following vaccination”.

The briefing document also states that in a subanalysis, a numerical (but non-significant) imbalance in the rates of spontaneous pregnancy loss (miscarriage) was observed in women vaccinated with Cervarix , but the findings "do not establish a causal relationship." The agency plans to evaluate long-term safety of the vaccine, “specifically the potential occurrence of autoimmune disorders and pregnancy outcomes" in two large Phase IV studies.

Staffers back Gardasil for male genital warts
The prospect of Cervarix to be competing soon with Merck & Co’s well-established jab Gardasil is therefore looking good. Analysts at Morgan Stanley believe that the GSK vaccine has the potential to grab more than a quarter of Gardasil’s current market.

However, Gardasil sales have slowed down of late and Merck also has a date with the VRBPAC on Wednesday where it is hoping to get backing for the vaccine as a treatment for preventing genital warts in males, which could add impetus to the franchise.

The FDA staffers issued a memo saying that Gardasil is effective at preventing genital warts caused by HPV types 6 and 11 in males between 16 and 26 years old. Merck is hoping to get an expanded approval covering males aged nine to 26, having been told by the FDA earlier this year that a bid to have the indication extended to the prevention of “external genital lesions”, which would have encompassed penile cancer, was too broad.