the drug discovery pipeline

Question 1

medicinal chemistry definition

Answer 1

the design + synthesis of a pharmaceutical agent/drug that has a desired biological effect on the human body (or other living systems)

Question 2

drugs definition

Answer 2

chemical substances used in treatment / cure / prevention / diagnosis of a disease or used to otherwise enhance physical / mental wellbeing

Question 3

give 2 features of ideal/good drugs

Answer 3

they should work effectively and have minimal side effects

Question 4

roughly how long does the drug discovery process take?

Answer 4

10-15 years

Question 5

state the stages in the drug discovery pipeline

Answer 5

1- target identification + validation
2- HTS (high throughput screening)
3- optimisation
4- preclinical development
CLINICAL TRIALS
5- phase I
6- phase II
7- phase III
LAUNCH
8- phase IV

Question 6

what is target identification + validation?

Answer 6

a biological target is found and the effect of an interaction + how such a drug may be useful is studied

Question 7

what is HTS?

Answer 7

molecule that interacts well with target is found - this is used as a basis for the next stage

Question 8

what is optimisation?

Answer 8

molecule is adapted and change in effects is observed, until the optimised ‘lead compound’ is found

Question 9

what is preclinical development?

Answer 9

drug is tested in models/cells/animals to determine serious side effects/toxicity
- the process up until now has taken about 4-5 years
- this stage lasts a further 2 years

Question 10

what is phase I of clinical trials?

Answer 10

drug is tested on healthy humans to determine safety + other side effects
- usually only involves a dozen or so subjects
- safer to stagger dosing participants, in case something goes wrong
- usually takes 1.5 years

Question 11

what is phase II of clinical trials?

Answer 11

drug is tested on sick humans to determine effectiveness against disease
- involves 100s of patients
- placebo is used to ensure effects are real/not psychosomatic, double blind usually
- lasts 2 years

Question 12

what is phase III of clinical trials?

Answer 12

drug is tested on sick patients to determine best dosage
- involves 1000s of patients, most comprehensive + expensive
- chance to detect rarer side effects + assess drug against other drugs/treatments
- double blind
- takes 3.5 years

Question 13

what is phase IV?

Answer 13

post launch trials, allow rarest side effects to be identified (1 in 100 000), tests effect on different ethnicities, or drug-drug interactions/ side effects, and long term side effects

Question 14

can the drug development process be sped up?

Answer 14

yes - in an emergency
in response to 2020 COVID-19 pandemic, pfizer initiated discovery efforts to identify an oral inhibitor to the virus in early 2020 and by feburary 2021 clinical trials had begun - this is incredibly fast
the drug received emergency use authorisation in the USA + UK

Question 15

POM meaning

Answer 15

prescription only medicine

Question 16

OTC meaning

Answer 16

over the counter
- drugs that have been around for a while can be switched to OTC if there is sufficient data proving its safety e.g. paracetamol

Question 17

how do companies decide which drugs to develop + a disadvantage of this?

Answer 17

the potential market - like all businesses, pharma companies are out to make a profit by prioritising diseases where a large return is likely
- this means that diseases common in rich countries get more attention, much less is given to diseases that affect poorer nations, and due to patent these countries get medicines much later due to cost

Question 18

is it moral to develop lifestyle drugs e.g. viagra instead of treating the many illnesses in 3rd world countries?

Answer 18

probably
but this is not an either/or - development into 3rd world disesaes is undergoing, but mostly taken on by non-profit organisations e.g. universities back by charity/ have less funding

Question 19

patent definition

Answer 19

a license granted by a government body that guarantees exclusive exploitation rights to intellectual properties

Question 20

why do governments grant patents?

Answer 20

it encourages innovation by giving companies a guarantee of return on a novel product/process otherwise they wouldn’t invest in R+D

Question 21

generics definition

Answer 21

versions of medicines manufactured by other companies

Question 22

give 2 ways patents are profitable

Answer 22

prevents other companies from stealing your drug, so you can upcharge for it if its the first in the market
patent infringement gives the patent holder the right to sue
patents can be licensed allowing other to use your invention if they pay royalties, can be very profitable in the right industry

Question 23

how long do patents last?

Answer 23

around 20 years, they are in public domain so after the expiration anyone can copy the drug and the owner loses its monopoly, allows price to fall dramatically

Question 24

why is timing crucial when choosing to file a patent?

Answer 24

the time scale of a patent starts from the day it is filed, not the drugs launch date
filing too early means reducing the years of sales monopoly to recoup costs of R+D, this is when most profit is made
filing too late risks another company beating you to it

Question 25

can patents be extended?

Answer 25

not generally, depends on circumstances companies try to prolong exclusivity on a drug by filing multiple, e.g. for therapeutic indication, manufacturing process, formulation, etc

Question 26

many analogues can be included in the patent - why is selecting these crucial?

Answer 26

not all these drugs/analogues necessarily will have been made claim too many prophetic compounds may cause patent to be rejected claiming too few leaves the door open for competitors, who may easily be able to reproduce an effective copycat without infringing the patent

Question 27

give 5 reasons why we need new drugs

Answer 27

- overuse of the same drugs can lead to resistance by the body/by pathogens - down regulation of receptor sites after repeated stimulation of receptors leads to breakdown so there are fewer receptors to act on - altered drug uptake if plasma membrane changes to prevent drug from entering/acting - improvement of disease treatment - production of safer drugs

Question 28

what is the hERG gene + why is it problematic?

Answer 28

this gene is related to a cardiac muscle cell potassium ion channel - critical for repolarisation + timing in the heart, interfereance can cause heart problems + death there is no x-ray crystal structure for hERG, difficult to know how it works hERG is a common reason why drugs fail in preclinical safety trials

Question 29

what 2 effects cause 90% of drug failures/withdrawals from the market?

Answer 29

hepatotoxicity + cardiovascular toxicity (e.g. hERG)

Question 30

API definition

Answer 30

active pharmaceutical ingredient

Question 31

what legal step must be done before drugs can be sold?

Answer 31

the drug must be approved by regulatory bodies, e.g. US FDA, UK MHRA, etc a license will only be issued upon completion of extensive safety evaluation, culminating in clinical trials