Week 10 - Modern Developments

Question 1

Approximately how many drugs exist to treat Malaria? Name a few.

Answer 1

~20

Aminoquinolines, arylaminoalcohols, artemisinines, antofolates, antibiotics.

Question 2

Why do we need to develop new anti parasitic drugs?

Answer 2

Most were designed for other uses.
Most are not fit for purpose.
High cost.
Poor efficacy.
High toxicity.
Natural or acquired resistance.
Need for hospitalisation and highly trained personnel.

Question 3

Briefly describe the drug discovery process.

Answer 3

1. Research into pathogens and diseases processes.
2. Effects of specific compounds on targets, in vitro and in vivo testing.
3. Clinical trials, scale-ups and manufacturing.

Question 4

Describe Phase 1 of drug testing.

Answer 4

Phase 1:
test experimental drug/treatment in a small group of people (20-80) for the first time to evaluate safety, determine safe dosage and identify side effects.

Question 5

Describe Phase 2 of drug testing.

Answer 5

Phase 2:
experimental treatment given to a larger group of people (100-300) to establish drug efficacy, usually against a placebo. Usually confined to high risk groups.

Question 6

Describe Phase 3 of drug testing.

Answer 6

Phase 3:
treatment given to large groups (1000-3000) to confirm effectiveness, monitor side effects, compare to commonly used treatments, and collect information on risk-benefit in demographically diverse groups.

Question 7

Describe Phase 4 of drug testing.

Answer 7

Phase 4:
post-marketing studies collect additional information, including observational monitoring at population level, collecting epidemiological data and evaluating cost effectiveness.

Question 8

Why are there few drugs for NTDs?

Answer 8

Only 13 drugs have been developed for NTDs since 1975.
Huge market but low price - monthly medication for ischaemic heart disease $105-$300 .
In NTD endemic areas, patients can often only afford $0.10 per treatment.

Question 9

What are PPPs?

Answer 9

Public-Private Partnerships

Academia, biotech’s and industry collaborate to discover, develop and deliver new medicines.
Allows for financial return on R&D investment from drugs for the poor.
Supported by charitable foundations, private and governmental organisations.

Question 10

What is MMV?

Answer 10

Medicines for Malaria Venture

Subsidise R&D without expectation of repayment.
New drugs priced solely on manufacturing costs.

Question 11

What is DNDi?

Answer 11

Drugs for Neglected Diseases initiative.

Develop large portfolio of novel and anti-NTD drugs.
Share knowledge and best practice across industry.

Question 12

What two main approaches to drug discovery are there?

Answer 12

Target-based (reductionist) approach.

Phenotypic (systems) approach

(Drug repurposing is also an option)

Question 13

What is the Target-based discovery approach also known as?

Answer 13

Reductionist approach.

Question 14

What is the Phenotypic discovery approach also known as?

Answer 14

Systems approach.

Question 15

What are the strengths of the Target-based approach?

Answer 15

The target’s predicted biochemical phenotype is known.

Rapid high-throughput assay.

Structure and mechanism based approaches are possible.

Question 16

What are the weaknesses of the Target-based approach?

Answer 16

It does not address key druggability issues (permeability, selectivity etc.)

It does not identify pro drugs or drugs acting via lethal synthesis.

Drug resistance is more likely, there is a shortage of validated targets.

Question 17

What are the strengths of the Phenotypic approach?

Answer 17

It addresses key druggability issues.

The assay yields desirable growth inhibition or death phenotype.

Identifies complex models of action.

Drug resistance is less likely.

Question 18

What are the weaknesses of the Phenotypic approach?

Answer 18

Target identification and mode of action can be challenging.

Lower assay throughput.

Law of diminishing returns. Toxicity issues more likely.