Private ENPV is dependent on the duration of each phase and the distribution of out-of-pocket costs throughout each phase. Often times, there are overlaps as well as gaps among phases. For example, while Phase 1 may last for nearly 20 months, a company may initiate Phase 2 trials after having completed its single ascending dose tier studies within the first 12 months of Phase 1. There are a number of published studies that provide estimates of average phase durations for pharmaceutical development accounting for these phase overlaps and gaps (see Table 7). None of these reported estimates, however, are specific to antibacterials which may have a different phase duration profile than the “average pharmaceutical.”
Based on the published information and discussion with experts and drug sponsors, the average pre-clinical and Phase 1 durations are set at 66.0 months (i.e., 5.5 years) and 10.5 months (i.e., 0.9 year), respectively. Further, assuming most new antibacterials will get priority review by the FDA, we estimate the NDA approval phase duration at 9.0 months (i.e., 0.75 year) in the model.5 Unlike pre-clinical, Phase 1 and NDA approval times, however, the timelines for Phase 2 and Phase 3 studies are expected to vary across the six different indications.
Table 7: Pre-clinical, Clinical, and NDA/BLA Application Average Phase Durations (in Months)
|Source||Pre-clinical||Phase 1||Phase 2||Phase 3||NDA/BLA|
|DiMasi et al., 2003||N/A||21.6||25.7||30.5||N/A|
|DiMasi et al., 2004 [c]||N/A||50.5||12.5|
|DiMasi & Grabowski, 2007 [a]||52.0||19.5||29.3||32.9||N/A|
|Adams & Brantner, 2006 [b]||N/A||19.0||30.0||30.0||15.8|
|Paul et al., 2010||66.0||18.0||30.0||30.0||18.0|
|Abrantes-Metz et al., 2004||N/A||19.7||29.9||47.0||N/A|
[a] The figures are applicable to biopharmaceuticals.
[b] The reported figures only include those based on the Pharmaprojects database.
[c] The reported figures are specific to anti-infectives.
Depending on the indication, Phase 2 and Phase 3 studies are expected to last from 10.0 to 18.0 months and 12.5 to 39.0 months, respectively (see Table 7). For sensitivity analysis, we again assume that each phase duration parameter has a triangular probability distribution with the following bounds:
- Pre-clinical: Lower bound of 52.0 months, upper bound of 72.0 months
- Phase 1: Lower bound of 9.0 months, upper bound of 21.6 months
- Phase 2
- ABOM: Lower bound of 12.0 months, upper bound of 30.0 months
- ABSSSI: Lower bound of 9.0 months, upper bound of 30.0 months
- CABP: Lower bound of 12.0 months, upper bound of 30.0 months
- CIAI: Lower bound of 10.0 months, upper bound of 30.0 months
- CUTI: Lower bound of 10.0 months, upper bound of 30.0 months
- HABP/VABP: Lower bound of 16.0 months, upper bound of 30.0 months
- Phase 3
- ABOM: Lower bound of 20.0 months, upper bound of 47.0 months
- ABSSSI: Lower bound of 10.0 months, upper bound of 47.0 months
- CABP: Lower bound of 10.0 months, upper bound of 47.0 months
- CIAI: Lower bound of 17.0 months, upper bound of 47.0 months
- CUTI: Lower bound of 17.0 months, upper bound of 47.0months
- HABP/VABP: Lower bound of 35.0 months, upper bound of 47.0 months
- NDA Approval: Lower bound of 6.0 months, upper bound of 12.5 months
5 Under GAIN, Antibacterial or antifungal drugs designated as Qualifying Infectious Disease Products will receive a priority review. The nine-month timeline used in our model reflects a slightly longer approval time given historical data and thus does not reflect the review and approval goals for FDA.