drug discovery

Question 1

outline the general path for drug discovery

Answer 1

Basic research and pre-clinical research (3-6 yrs)
Clinical research (three phases, 6-7 yrs)
Regulatory review (0.5-2yrs)
After about $1 billion, the drug can go to market

Question 2

who funds the research?

Answer 2

Large pharmaceuticals like GSK fund this research, hold the patents but also all the risk
Contract research organisations for the actual research, day to day (paid the same in success or failure)

Question 3

how does a drug discovery process get started?

Answer 3

Decide what disease area you want to work in, understand it fully
Pick a target (receptor, enzyme, transport protein etc…)
Target assays to see what drug works against your target (discovery scientist)
Lead selection - which drug is going to be most successful (efficacy, toxicity, side effects, done by exploratory toxicologists)

Question 4

what is involved in pre-clinical trials?
what was lethal dose 50?
what are the three Rs?

Answer 4

Preclinical development - define safety margins and dosage, what organs are affected in an overdose etc… by animal testing

For small molecules, they used to do lethal dose 50 - what dose kills half the subjects

Today the three Rs must be followed - reduce, refine and replace
Must be done on a rodent and non-rodent species (default is rat and beagle)
Three dose groups - low (no toxicity), intermediate and high (what does an overdose look like)
Obtain regulatory approval for clinical trials

Question 5

what is toxicokinetics?

Answer 5

PK profiles developed to determine min effective dose, max non-toxic dose and pick a dose for human trials
Identify specific monitoring requirements (e.g. which organs)

Question 6

what are the 6 musts before going to human trials?

Answer 6

Evidence of pharmacological activity

Maximum non-toxic dose

Adverse effects on target organs

Relationship of effects to dose and exposure

Differences observed in different species

Evaluation of risk in humans

Question 7

explain the three phases of clinical trials

Answer 7

Phase 1:
In healthy volunteers
Is it safe, well tolerated? What are the pharmacokinetic properties
Phase 2:
To patients
How much should be given to be effective
How well does the treatment work
Phase 3:
1000+ patients
Must be multinational with definitive results

unofficial kind of phase 4: Drug goes to the market and is under surveillance to detect long term adverse effects
Several drugs have been withdrawn post-market after many years or as short as 6 months

Question 8

after a trial gone wrong, what do many companies now do in their research?

Answer 8

receptor-occupancy studies