Future challenges

Question 1

migraine drug effect

Answer 1

target CGRPs - neuropeptide (sensory and trigeminal neurons), increase circulation during migraine, has RAMP1 accessory protein
36 years until approval

Question 2

CGRP antagonist

Answer 2

olcegepant and telcagepant

Question 3

process of migraine drug

Answer 3

CGRP large and very complex = screening of chemical libraries
use over expressed cell model and plasmid DNA encoding receptor - human humour cell like = naturally express CGRP (not stable)
target engagement/efficacy can’t use animal model (can’t model migraine) = measure blood flow (potent vasodilator)

Question 4

olcegepant and telcagepant pharmacokinetics

Answer 4

olcegepant not orally bioavailable

telcagepant - low primate bioavailability and high first pass metabolism = need high doses

Question 5

olcegepant results

Answer 5

better against placebo - 60%, 2h post dose

discontinued = IV

Question 6

telcagepant results

Answer 6

increase in liver enzyme activity detected = possible hepatotoxicity
withdrawn

Question 7

monoclonal antibody drug

Answer 7

aimovig/erenumab - injection (less frequent)
binds to CGPR peptide to produce antagonist effects
preventative
expensive, difficult, slow clearance (side effects last longer), serious constipation?

Question 8

societal needs

Answer 8

medicines to treat or cure all disease
medicines that are personalised
medicines that are available to all who need them
medicines that are safe and effective

Question 9

medicines to cure or treat all disease

Answer 9

7/10 leading causes of death are chronic

DALY and burden taken into account

Question 10

DALY

Answer 10

disadvantaged life year
top FDA = neonatal, cardiovascular, respiratory illness
increasing DALY in diabetes and alzheimers

Question 11

top FDA approval areas

Answer 11

cancer, neurology, infectious disease (too high), diabetes, imaging
NOT - cardiology, neonatal

Question 12

why does the FDA not approve the right medicines

Answer 12

need to know disease mechanism/targets
need animal models that can translate
need funding = high risk when unknown (more safety requirements)

Question 13

changes to get more medicines

Answer 13

more funding = better models, take more novel drugs

rare diseases = however, need more patients to be stat sig

Question 14

medicines that are personalised

Answer 14

same dose and same application to everyone despite different response
most drugs more ineffective than helpful

Question 15

types of responders

Answer 15

effect responders, non responders, adverse effects responders

Question 16

changes to tailor medicines

Answer 16

identify why only some respond/why some react badly
genetics, metabolism, biomarkers
class individuals/subpopulations
assay pharmacokinetics thoroughly, CYP levels, males vs females

Question 17

medicines available to all who need them

Answer 17

1.3B USD to get to market - costs rising as more biologics come out
average price anticancer = US $100,000 one year/course
25% individuals struggle to afford = don’t fulfil prescription, cut/skip pills

Question 18

parmac spending

Answer 18

less than any other country
only 30% of those funded in other countries
7/90 anticancer, no diabetes

Question 19

essential medicines list

Answer 19

minimum needs met that are safe efficacious and cost-effective
good distribution/supply, appropriate storage, dose quality, administration, affordable

Question 20

medicines that are safe and efficacious

Answer 20

generic drugs have different inactive ingredients = no clinical trials and low cost
may not metabolise the same
counterfeit drugs = false packaging, lower dose, contaminants -> costs are driven up further to increase regulation

Question 21

make a profit

Answer 21

drug trials expensive to establish link between drug, target and disease = 1 billion, 10-15 years
discover 10,000 -> 1 success

Question 22

risky ventures

Answer 22

large, long term investment with high risk of failure
potential return high
govt and non profit don’t invest

Question 23

pharmaceutical company priorities

Answer 23

drug -> large number of patients that can pay (insurance or govt)
= chronic diseases in developed world

Question 24

Reducing costs

Answer 24

reduce time = chemicals less complicated + standardised + established
out of pocket expenses = out source to do trials
fail earlier by better preclinical testing for efficacy and safety

Question 25

major costs

Answer 25

patients, quality control, clinical trial complexities, regulatory hurdles

Question 26

patents

Answer 26

earn recognition - financially
composition or formulation or disease applications
new and not obvious
provisional (18 months), 20 years
reduce income when end
need one in each country - expensive

Question 27

me-too drugs

Answer 27

avoid patents - sufficiently different
improve ADME/Tox, reduced risk
same targets

Question 28

clinical trial complexities

Answer 28

interactions with disease, drug, host -> need patient stratification
safety and efficacy balance
high attrition (pull out)
enrolment targets (inclusion/exclusion, ethics, outcome measures hard to measure, study size)

Question 29

improve reputation

Answer 29

working conditions and pay in supply chain
access to medicines in society and third world
decrease pollution and environmental impact, water use