entrepreneurship in biotechnology columbia university graduate school of arts and sciences biot 4180...
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Columbia University GSAS BIOT 4180
Entrepreneurship in Biotechnology
Columbia UniversityGraduate School of Arts and Sciences
BIOT 4180
Columbia University GSAS BIOT 4180
Week 10
Product Development:Clinical Development
Development Process
Columbia University GSAS BIOT 4180
Decrease in productivity
Columbia University GSAS BIOT 4180
Academia and Private Sector
Columbia University GSAS BIOT 4180
Risk mitigation
Columbia University GSAS BIOT 4180
Columbia University GSAS BIOT 4180
Process
• Phase 1: safety– IND: Investigational New Drug– Apply to FDA for human dosing– FDA has 30 days to object
• IRB approval• Small number of subjects, one dose– Records adverse events, monitor physiologic
process– Efficacy signals in oncology, infectious disease
Columbia University GSAS BIOT 4180
Phase 2 trial
• IIA: dosing• IIB: efficacy– Target dose for pivotal– Target indication, study design
• Can do one at a time or many phase 2 trials– Small biotech companies do a minimum – Large pharma do wide range of studies
• Rarely file NDA/BLA based on phase 2 data
Columbia University GSAS BIOT 4180
Phase 3
• Typically 2 trials per indication, multicenter• N=hundreds to thousands• Why do trials fail?– Poor design• Difficult identification of treatment group or endpoint• Poor statistics: gaussian distribution, power• Placebo groups perform better than historical• Poor oversight
– The drug does not work
Columbia University GSAS BIOT 4180
Phase 3 considerations
• Physiologic or made-up endpoint– ADAS-COG and other cognition tests– Pain scores– How reproducible is the entity being measured?
• Surrogate endpoints: accelerated approval process
• Dealing with drop-outs– Intent to treat vs per protocol
• Ease of enrollment
Columbia University GSAS BIOT 4180
Post phase 3
• Successful trial– Second trial (unless oncology, unmet need)– If works: NDA, then PDUFA date (6-9 months)– If approved, marketing and phase 4 studies
• Unsuccessful trial– Data review/ data mining– Await concurrent study completion– Tough to kill a molecule
Columbia University GSAS BIOT 4180
Decrease in # approved drugs
Columbia University GSAS BIOT 4180
Increase in orphan designations
Columbia University GSAS BIOT 4180
Orphan Designation
Columbia University GSAS BIOT 4180
Definitions
• Accelerated approval: surrogate endpoint• Fast track designation: FDA facilitated
communication• Priority review: 6 vs 10 months• SPA Special Protocol Assessment• PDUFA• IND process• NDA