Good News for Cervarix?

GlaxoSmithKline sees a light at the end of the tunnel for Cervarix at FDA; but the company is not ready to break into a mad dash to reach that light.

That’s the message from the June 30 update on GSK’s filing for the bi-valent/adjuvanted human papilloma virus vaccine. On June 30, the company said it had answered specific questions posed by FDA in its “complete response” rejection of the application at the end of last year (see here).

But GSK doesn’t want FDA to make a decision on the application as it stands now. GSK wants to add final data from an 18,000-pateint Phase III study (HPV-008 or NCT00122681 by its ClinicalTrials.gov name) before seeking a FDA decision.

GSK says that 008 will be completed this year and data will be submitted in the first half of 2009. The company says to expect “up to six months” following submission of the data for FDA to review the amended application. The company had reported in the spring that the final data collection should take place in September. The trial is being conducted at 178 centers in 14 countries. GSK is using hepatitis A vaccine as the control.

The primary reason for the update is that GSK originally said it would take about six months to answer FDA, and the review of the first high-visibility product with a new adjuvant is being closely watched by the vaccine field and by Wall Street.

But there are other reasons for GSK to step forward with Cervarix info now. Some of its competitors in the vaccine world have been releasing information recently that is increasing skepticism about the GSK model for an HPV vaccine.

Novartis told analysts on June 4 that it is finding the route for an adjuvanted flu vaccine through FDA trickier than it thought (see here). Jorge Reinhardt even described his adjuvant (MF59) as not a very pharmacologically active ingredient to help assure analysts that it could eventually make it through FDA’s safety review.

Merck turned a bit a bad news for its HPV vaccine Gardasil into worse news for GSK on June 25. Merck reported a “complete response” rejection from FDA on a supplemental application for Gardasil for older patients (women 27-45). Merck rules the HPV market alone in the US while GSK is stalled. Rejecting the application, FDA said that one of the claims that it did not accept was the idea that Gardasil could protect against HPV strains beyond the four specifically included in the vaccine (6,11,16, 18).

That rejection of the “cross-protection” claim is what hurts GSK. With only two strains covered, GSK has been banking on acceptance of a cross-protection claim to make its bi-valent match up to Merck’s quadra-valent product.

The rejection for Merck is one of those subtle regulatory situations where the sponsor is hurt but probably not nearly as badly as one of the sponsor’s competitors. Merck’s bad news may well be another reason why GSK is taking a measured approach to finding the end of the tunnel.

A GSK Success

One more note from the tough slog to the new world of adjuvant products--and this one relates to a GSK success. Its pre-pandemic flu vaccine (Prepandrix) was approved in Europe earlier in the year with a proprietary adjuvant. The company has tried to maintain a mystique around the special secret ingredient during development (See here). Most competitors thought it was an adjuvant called AS03, but GSK wouldn't say a word.

The secrecy is over. GSK had to make the ingredient public in final registration documents with the European Medicines Agency, made public at the beginning of June.

Lo and behold, the secret ingredient is AS03, composed of squalene (10.68 milligrams), DL-alpha-tocopherol (11.86 milligrams) and polysorbate 80 (4.85 milligrams). Not much of a secret after all. GSK, though, defends the attempt to create mystery around the adjuvant on the way to approval in Europe as sound competitive practice.

Well, it certainly caught our attention. Maybe it built some hype with public health officials as well.

Prepandrix, and its adjuvant, are undergoing clinical trials in the US. The vaccine would be made for North America in Quebec City at a different plant from the European product. It apparently has a long way to the end of the regulatory tunnel too. Every company with a stake in the adjuvant development effort should hope that GSK is as careful at preparing an application for the product as it was at tryingto keep the ingredient secret during development.