Bavarian Nordic A/S this week announced results from a pivotal Phase 2 study of freeze-dried, thermostable IMVAMUNE smallpox vaccine supporting the clinical requirements for an Emergency Use Authorization, which would allow for stockpiling of this next-generation of the vaccine.
In addition, the company announced positive results from the first of two pivotal Phase 3 studies of the liquid-frozen formulation of IMVAMUNE supporting a Biologics License Application for U.S. approval of the vaccine.
The Phase 2 study compared the safety and immunogenicity of a freeze-dried and a liquid-frozen formulation of IMVAMUNE and enrolled 650 healthy subjects who were randomized to receive either formulation of IMVAMUNE.
The freeze-dried vaccine induced an equivalent antibody response as the liquid-frozen version, meeting the primary endpoint of the study. Also both formulations recorded a similar safety profile, confirming that the clinical data generated cumulatively in more than 7,600 vaccinated subjects is relevant for both formulations of IMVAMUNE.
The results provide the final clinical data required to support stockpiling of the freeze-dried version of IMVAMUNE in the U.S. Strategic National Stockpile. Supported by a contract option of USD 22 million exercised by the Biomedical Advanced Research and Development Authority (BARDA) in 2014, Bavarian Nordic is currently working to transfer the freeze-drying process to a new manufacturing line with a larger commercial capacity. These manufacturing activities remain on-track to be finalized this year, which is the final step towards meeting the regulatory requirements to stockpile the freeze-dried version of IMVAMUNE.
“Completing this pivotal Phase 2 study is a significant step in the transition to the freeze-dried version of the vaccine, which provides a number of advantages for the future procurement and stockpiling, thereby broadening the commercial potential,” said Paul Chaplin, President and Chief Executive Officer of Bavarian Nordic. “We remain on track to complete the transfer of the manufacturing process which will enable us to start deliveries in 2016, as we look forward to continuing our successful long-standing collaboration with the U.S. Government on their public health preparedness.”
The Phase 3 was designed as a randomized, double-blind, placebo-controlled study in 4,000 subjects. Three thousand (3,000) subjects were vaccinated with three different manufacturing lots of the liquid-frozen IMVAMUNE formulation (1,000 subjects per lot) and compared to 1,000 subjects that received placebo. The three lots of IMVAMUNE induced equivalent antibody responses, meeting the primary endpoint of the study, while the favorable safety profile of IMVAMUNE was confirmed in this largest clinical study performed to date.
Despite close cardiac monitoring of all subjects, no serious adverse reactions were reported among the 3,000 subjects vaccinated with IMVAMUNE, confirming the results of a smaller Phase 2 placebo controlled study that was recently published and clearly differentiates the safety profile of IMVAMUNE when compared to traditional smallpox vaccines (e.g. ACAM2000® approved in the U.S.) that have recorded high rates of cardiac complications in healthy recipients (5.73 events per thousand immunizations).
The Phase 3 study also received funding from BARDA under Contract No. HHSO100200700034C.
