1. The overall probability of progression from phase 2 trials to FDA approval within 10 years was 1 in 10.
2. The average time from phase 2 to licensure was roughly four and a half years, although this period ranged from mere weeks to over a decade.
Evidence Rating Level: 2 (Good)
Study Rundown: With nearly 30 of 50 candidates advancing to phase 2 testing within months and multiple companies (Pfizer, Moderna, and AstraZeneca) already unveiling preliminary results from phase 3 trials, the development of vaccines against SARS-CoV-2 has been proceeding at breakneck pace. Despite these highly promising results, success is far from certain; one possibility that must be considered is the occurrence of various unanticipated setbacks such as vaccine-dependent enhancement, an effect that may not be immediately evident. While previous studies have examined some potential variables affecting the pace and probability of success of vaccine development, those were generally performed using clinical data from the previous decade. In order to account for the impact of recent technological advances such as next-generation sequencing and angstrom-resolution imaging, this study investigated all vaccines for emerging and reemerged viral infectious diseases (EVIDs) with clinical trials of any phase since 2005, a year which marked the inception of several new vaccine development approaches. After accounting for over 20 EVIDs, under 80 vaccines were found to have completed phase 1. Of these, only 9 ultimately advanced to approval, the fastest timeline being under 2 months and the slowest reaching nearly 14 years. While the overall probability of success (POS) within 10 years was 1 in 10, the exclusion of pandemic influenza trajectories lowered this number to only 1 in 30. This study offered a broad overview of the success probabilities and timelines of vaccines against viral diseases, but further research is needed to identify specific factors influencing movement through the development pipeline.
Relevant Reading: Clinical development success rates for investigational drugs
In-Depth [retrospective cohort]: This study utilized public data from ClinicalTrials.gov between 1 January 2005 and 22 March 2020 to identify 606 prelicensure trials involving 220 vaccine candidates. Only 76 candidates qualified for the primary analysis by progressing beyond phase 1, which reduced the the number of resolvable EVIDS from 27 to 23 (HIV, H5N1, Ebola, H1N1, H7N9, Zika, Universal flu, EV71, Dengue, West Nile, Chikungunya, H3N2v, Hepatitis C, Marburg, MERS, Smallpox, Yellow fever, Hantavirus, CCHF, H10N8, Lassa, Nipah, and Rift Valley). Of these 76 trajectories, only 9 were ever approved (shortest timeline, 6.4 weeks; longest timeline, 13.9 years), and only 7 were approved within 10 years of phase 2 start, corresponding to a Kaplan-Meier estimate of the POS of 10.0% (95% CI, 2.6% to 16.9%). After excluding pandemic influenza trajectories which primarily capitalized on an existing platform, the POS was reduced to merely 3.2% (CI, 0.0% to 9.2%). The probabilities of transition from phase 1 to phase 2 and from phase 2 to phase 3 were similar (38.2% [CI, 30.7% to 45.0%] versus 38.3% [CI, 23.1% to 50.5%]), but 61.1% (CI, 3.7% to 84.3%) of candidates that reached phase 3 were eventually granted approval. Vaccine type was found to have a major effect on POS, with only split virus vaccines (POS, 56.4%; CI, 12.6% to 78.2%) and nucleic acid vaccines (POS, 5.9%; CI, 0.0% to 16.4%) obtaining licensure within 10 years.
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