Risk in Vaccine Research and Development Quantified

Abstract

To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates) have been published for new chemical entities (NCE), little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines.

Role of small biotechnology companies in the fledgling biodefense vaccine industry

“…This appears to be the most common path, and only a few small biotechnology companies make the leap into mid-size or publically traded companies (for example, Novavax, Emergent Biosolutions, and Inovio Pharmaceuticals). The path to commercial product licensure takes an average of 10 years and $200-900M from 'bug to drug' if continuous funding is provided [20]. Gaps in funding will stall or completely halt development of 'government interest only' MCM, thus requiring commitment on the part of these well-funded pharmaceutical companies for successful delivery of MCM.…”

Improving vaccine trials in infectious disease emergencies

“…A dengue vaccine, although beneficial overall, was found during Phase III (14) to be harmful to certain identifiable recipients (15). Remarkably, while not always due to trial outcomes, a third to a half of vaccines that enter Phase III fail to submit for regulatory approval (16, 17). …”

Organizing the HIV vaccine development effort

“…In-depth knowledge of the pathogen and immune responses do not guarantee that a vaccine approach tested in the preclinical studies will be safe, efficacious and practical in humans. This well-known gap--the product development “valley of death”--is especially large for HIV vaccines due to multiple scientific challenges and the very high bar of cost, human resources, and time for efficacy testing of candidates (1,2). A successful HIV vaccine will require severely tiered pricing to have a public health impact in areas where the epidemic is most destructive, which adds uncertainty about whether a private company will be able to recoup its research and development costs.…”