Drug discovery and evaluation

Question 1

How much does it typically cost to bring a drug to market?

Answer 1

about a billion

Question 2

T/F most drugs distributed today are generic

Answer 2

T - about 90%

Question 3

The Reverend _____ (1760s) found that the bark of the willow was effective in reducing fever

Answer 3

Edward Stone

Question 4

_____ (antibiotic) – discovered by Fleming (and others)

Answer 4

Penicillin

Question 5

_____ (anxiolytic) – 1st benzodiazepine, discovered by Sternbach.

Answer 5

Librium

Question 6

______, the active metabolite of an early class of antibiotics had diuretic side effects modified to form chlorothiazide (diuretic)

Answer 6

Sulphanilamide

Question 7

______ is a series of activities, which aim to
build confidence that a drug which acts by modifying the function of the target will deliver the efficacy and safety required

Answer 7

Target validation

Question 8

Types of screening to generate hits

Answer 8

Functional assay
Binding assay

Question 9

What are CAR-T Cells?

Answer 9

Chimeric antigen receptors (CAR) are a specialized gene that binds to proteins on patients cancer cells and is added to T cells in the laboratory. CAR T-cell therapy is used to treat certain cancers

Question 10

What kinds of things will preclinical testing assess for?

Answer 10

Detect potential hazards, explore maximum achievable doses, and monitor safety in humans to suggest ‘markers’

Question 11

Types of phase 1 clinical trials (done in a small number of “healthy” subjects)

Answer 11

 first exposure in humans
 single dose tolerability
 multiple dose tolerability
 dose-ranging based on animal doses

Question 12

Phase 1 study criteria

Answer 12

• study size: 20-100 human subjects
• Time: several months
• ~70% proceed to Phase 2

Question 13

Reasons for phase 1 failures

Answer 13

 pre-clinical animal models ≠ behavior in humans
 inadequate preclinical data
 change in drug formulation between time of
preclinical and clinical testing
 Pharmaco-kinetic/-dynamic relationships
 poorly designed clinical studies
 drug too toxic in humans

Question 14

Phase 2 trial criteria

Answer 14

• objectives: testing an hypothesis of no
  difference; safety
• types of studies: small controlled trials in
  intended patients
• dose ranging
• study size: usual <100 but could be up to
  several hundred subjects
• time: several months - 2 years
• ~33% move on to next phase

Question 15

Which phase of trial is completed on targeted patients?

Answer 15

Phase 3

Question 16

What percentage of patients pass phase 3?

Answer 16

~25-30% move to next phase (~6 out of the initial 100 at Phase 1)

Question 17

Reasons for phase 2 and 3 failures?

Answer 17

• adverse reactions
• drug-drug interactions
• drug-disease interactions in ill
  patients
• genetic – pharmacogenomics
• effectiveness insufficient (20%)
• economic (24%)

Question 18

How long does the FDA have to review a nre drug and product license application? (NDA/PLA)

Answer 18

180 days

Question 19

Limitations of the drug approval process

Answer 19

Trials lack size to detect rare adverse
events
Trials time too short to detect long-
term adverse effects