Cervarix: Big Step for FDA; Can GSK Make the Decision Easier?

Citi's Kevin Wilson is out with a comment on Glaxo's pending Cervarix application at FDA that seems right on point to us.

Extrapolating from some forthright comments by a senior official from FDA's vaccine review division on January 30, Wilson surmises that FDA is feeling the pressure of a big decision on the new generation of vaccine adjuvants -- especially those that may act on toll-like receptors to trigger the innate immunity system in the body.

FDA's Office of Vaccine Research & Review deputy director Florence Houn gave a presentation (of her personal views) on January 30 (see here). She noted concern that the agency does not fully understand the mechanism of action of adjuvants which enhance immune response. And she noted pointedly that the products will get used on broad populations.

The wide array of adjuvants under development for use in vaccines -- to improve the protective qualities of the products, to permit the use of lower doses of antigens, and to confer proprietary positions on the product sponsors -- represent a major step for the industry and a major risk for regulators. We have been saying that for over a year and a half (see here): adjuvants are a big opportunity, but they require a big decision from FDA.

As the new products with adjuvants approached the market, FDA tried to assuage concerns that there might be unusual regulatory burdens by saying that the current system for reviewing new products was adaptable to applications of products with adjuvants.

Now that the regulators face the prospect of having to make a decision on products that could go into wide use rapidly following commercial approval, the agency may be having second thoughts. Cervarix, after all, is headed into a big market, especially if GSK tries to compete strongly head up against Merck and Gardasil.

National Institute of Allergies and Infectious Diseases head Tony Fauci is generally an advocate for the new adjuvants. His institute has been aggressively funding work on adjuvants for the flu vaccines as well as other products. Even he, however, recognizes the pressure on FDA with the first approval of a product with an new adjuvant.

Fauci has said publicly that he understands why FDA would get cautious as the final decisions approach. He told an Institute of Medicine session on drug development at the end of 2007 that he recognized why FDA would want to examine these first applications carefully.

FDA's Houn spent a good part of her presentation pointing out that the agency is getting more interested in risk management programs for vaccines as well as drugs. She noted that the Acambis smallpox vaccine carries a full RiskMAP program--even though the product will be used primarily in the very controlled military patient population.

Reading further between the lines of Houn's speech, maybe risk management plans offer the way out for sponsors of the new adjuvant products.

Sponsors could relieve some of the pressure facing the agency by agreeing to programs to track the products broadly in the post-market arena. That is costly, but it may be one way to break what appears to be a developing log-jam over the new generation of vaccines.

This looks like a landmark decision for FDA, not an impasse. It will be interesting to see what GSK does to smooth the process.