Entrepreneurship in Biotechnology Columbia University Graduate School of Arts and Sciences BIOT 4180...

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