Novartis’ recently sanctioned unadjuvanted influenza A (H1N1) 2009 monovalent vaccine may be effective at just half the dose currently stipulated under its FDA approval, according to interim data from ongoing clinical trials. The studies also showed that combining the H1N1 vaccine with Novartis’ EU-sanctioned MF59® adjuvant could potentially quadruple vaccine supply.
The data emerged from pivotal clinical studies evaluating the immunogenicity, safety, and reactogenicity of both MF59-adjuvanted and unadjuvanted, inactivated A (H1N1) 2009 monovalent subunit virus vaccine in 4,080 adult and pediatric U.S. subjects. The unadjuvanted A (H1N1) vaccine was sanctioned by the FDA in September at the 15-microgram dose.
Trial results suggest that a single, 7.5-microgram dose of the unadjuvanted vaccine fulfilled immune response criteria associated with protection in adults and the elderly. Moreover, a single, 3.75-microgram dose of the MF59-adjuvanted A (H1N1) 2009 vaccine met serological protection criteria in children aged 3–8 years as well as adults and the elderly. Novartis says that more data in children and adults and initial data from infants aged 6–36 months are expected in December.
The company is now discussing the trial results with the FDA and is carrying out additional statistical analyses. Evaluation is ongoing to determine whether the antigen content per dose can be reduced in the U.S.
“This promising data suggests that many more people could potentially be vaccinated with our current vaccines supply,” comments Andrin Oswald, CEO vaccines and diagnostics. “The data also confirms the antigen-sparing potential of our proprietary adjuvant, MF59. The vaccines output of our Liverpool, U.K.-based flu manufacturing facility, fully dedicated to the U.S. since the emergence of the pandemic, could be quadrupled if vaccines are adjuvanted.”
Novartis’ influenza A (H1N1) 2009 monovalent vaccine is manufactured using the established egg-based platform used to generate its Fluvirin® seasonal flu vaccine. At the end of October Novartis confirmed that it had shipped 7.5 million ready-to-use doses of its unadjuvanted Influenza A (H1N1) vaccine to the U.S. and expected 25 to 30 million doses of the vaccine to be available in prefilled syringes and multidose vials by the end of November. The HHS has also contracted the company to produce 90 million doses of MF59 by the end of November.
Although the MF59 adjuvant is not a component of any FDA-approved vaccines, it is licensed for use in Europe as part of the seasonal flu vaccine, Fluad®. The two A (H1N1) vaccines, Focetria® and Celtura®, also contain MF59. During November the company received marketing clearance in Germany and Switzerland for Celtura, which is a cell culture-based vaccine. In September Focetria received a positive opinion from the EMEA’s Committee for Medicines for Human Use. Focetria was originally approved by the EU in May 2007 as a mock-up file to be used once the WHO declared a pandemic.