Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines.

Development pathway for biodefense vaccines.

At the present time it is estimated that the process of development of a vaccine from discovery to licensure takes approximately 18-20 years and costs in excess of US$500 million. For "routine" vaccines, the case for developing a vaccine is straightforward in terms of economics and large scale public health utilization each year. For vaccines used for biodefense and emerging diseases, the considerations are somewhat different as the vaccine may not be needed every year to control outbreaks and may be stockpiled only as a countermeasure that hopefully may never be needed. Furthermore, efficacy trials are often difficult as the natural disease may be rare or not present. Consequently, animal models will play a critical role in demonstrating efficacy. Nonetheless, the vaccine pathway still requires the same fundamental components of basic science/discovery, preclinical development, clinical trials, registration/licensure, and a plan for implementation.

Arilvax (PowderJect).

Celltech (formerly Medeva) had developed Arilvax, a single-dose, live, attenuated vaccine for the prevention of yellow fever, which the company launched in Europe. However, in October 2000, PowderJect acquired the vaccine as part of its acquisition of Celltech's vaccine business [381557], [384374]. In July 2001, PowderJect expected to re-launch Arilvax in the UK and, in the near future, Europe, following a manufacturing upgrade [414453], [443490]. By May 2000, Acambis (formerly Peptide Therapeutics), was developing the vaccine in the US under an exclusive license and phase III trials were underway [341301], [366663]. By September 2000, preparation for a BLA in the US had begun [382969]. By September 2001, the BLA submission was expected by mid-2002 [422760], [443490]. In September 1999, Peptide Therapeutics was predicting a US launch in the first half of 2001 with expected sales of around US $25 million per annum [340078], [341301].