GSK submits Cervarix vaccine to FDA

The world's second-largest pharmaceutical company, GlaxoSmithKline (GSK), has submitted a Biologics License Application (BLA) for Cervarix, its cervical cancer adjuvanted human papillomavirus vaccine, to the US FDA.

If licensed, the vaccine will be indicated for the prevention of cervical cancer and precancerous lesions associated with the most common cancer-causing human papillomavirus types. For this candidate vaccine, GSK selected a novel proprietary adjuvant system called AS04, intended to enhance immune response and increase duration of protection.

The BLA for GSK's cervical cancer candidate vaccine included data from clinical trials in almost 30,000 females aged 10 to 55 years and reflected an ethnically diverse population. The submission also contains data from the largest phase III cervical cancer vaccine efficacy trial to date, which was conducted around the world in more than 18,000 females aged 15 to 25 years.

The GSK cervical cancer candidate vaccine is formulated with a proprietary adjuvant system called AS04. Published data have shown that the adjuvanted candidate vaccine provided a stronger and longer lasting immune response, compared with the same GSK vaccine composition formulated with a traditional aluminium hydroxide adjuvant.

However, US pharmaceutical company, Merck & Co has beaten GSK to the main markets of the US and the EU with its HVP vaccine, Gardasil, which costs USD 360 for a full course of three injections over a three month period and could be a big earner for the company.

Despite the wide take up and active marketing push, the efficacy of and need for Gardasil has been questioned. An article in the Journal of the American Medical Association (JAMA) suggested that in women aged 14 to 24, the rate of all 37 types of sexually transmitted human papilloma virus (HPV) combined was 33.8 per cent, which was much lower than the 50 per cent figure cited by Merck. Also, the rates for HPV types 16 and 18, which are the two main cancer-causing viruses cited by both companies, were much lower than expected: only 1.5 and 0.8 per cent, respectively.

Also, in the February 2007 edition of the American Cancer Association Guidelines reported that most HPV infections, even cancer-forming ones, disappear without treatment. Around 75 per cent of infections in adults and 90 per cent of those in adolescents resolve spontaneously.

According to US media reports, Merck's drug trials followed women who received Gardasil for an average of less than three years, so how long the immunity lasts or the long-term risks associated with it remains unknown. Children vaccinated in middle school could potentially lose their immunity by the time they were seniors in high school.

Sanford C Bernstein analysts have been reported as saying that GSKís head-to-head study should erode some of the market gains made by Gardasil, because strong data shown in past Cervarix studies suggest that it should at least be equal to Gardasil in effectiveness. They add that projects that Gardasil sales will lead Cervarix by USD 1bn annually, primarily because Merck beat Glaxo to the market and annual sales estimates of USD 2.5bn for Gardasil and USD 1.5bn for Cervarix have been considered as conservative, compared with other valuations.