L1 + L2: Drug discovery and development pipeline part 3 Flashcards
the place of clinical trials in drug development?
preclinical: discovery, pre-clinical. patent granted. 0-5 years
clinical: 5-14? years. phase 1, phase 2, phase 3
post market: 14?-25 years. phase 3, patent expoires, generics
atent is given the moment you identify a new molecule. Patent runs out in 20 yrs time. When runs out other companies can manufacture the drug at a much lower cost (generics).
Pre clinical 5 yrs
Clinical another 6-7 years (check on graph)
Phase 1 - drug to healthy volunteers. Check if drug prod adverse effects. Still dont know at that stage if drug will be effective. Think will be effective and safe at pre clinical. Can take blood samples from healthy volunteers and look at plasma-time curve etc.
Phase 2 - find out if drug is effective. Drug given to patients with disease you are trying to treat. Check if initial hypothesis is good- confirmation. Too many drugs get to this stage and fail.
Phase 3 - data from several hundred or several thousand patients. See if drug is better than current available treatment. Start to detect the less common side effects.
Then reg authorities give lisence to sell drugs.
Phase 4: post-marketing surveilance. Ongoing all the time. Now drug is out in the market. Hundreds of thousands taking drugs. Rare side effects start to emerge. doctor/gp gives drug. If go back about side effects, doctor fills in form to central data base. So rare side effects emerge. Drug could be withdrawn. E.g: operin. Arthirirus drug. Caused photosensitivty so had to be withdrawn.
regulatory approval?
What is regulatory approval?
It is a contract;
Between the Health Authority
MHRA (UK), FDA (USA), EMEA (Europe), MHLW (Japan), CFDA (China), CDSCO (India)
Represent ‘society’
Protects public health & safety
Ensures drug produces clear benefit to patients
And the Pharmaceutical Company
Permission to market the drug product for a specific indication
Owns the documentation used for assessment
Collects, compiles & evaluates safety & quality data
Pharmaceutical company presents safety and efficacy so reg bodies assess and approve.
regulatory documentation?
Regulatory documentation
Basis for assessment of the application
Describes
Quality: Chemistry & Pharmaceutics
Pharmacology
Pharmacokinetics, ADME
Toxicology
Efficacy assessment (studies in humans)
Often in a standardised format
Regulatory Authority guidelines
ICH Common Technical Document approach (Europe)
If successful will be issued with an “Approvable Letter”
Covers indication, labelling, monitoring, product Information
In the relevant territory
Product can now be sold to patients
Reasons for drug failiure
safety
PhI/II failures
Need for better “safety pharmacology”
efficacy
Ph II/III failures
More costly
Need to better understand disease and disease mechanisms
Need to improve preclinical – clinical predictivity
economics
Poor return on investment
Entering an already crowded market
Too short period of market exclusivity
Need to better understand pharmacoeconomics.
drug development success rates?
Drug Development Success Rates
First human dose (Phase 1 trials)
~90% of drugs fail and do not make it to market.
Only ~10% succeed and progress to later phases.
First patient dose (Phase 2 trials)
75–80% of drugs fail and do not make it to market.
Only ~20–25% succeed and move to Phase 3 trials.
First pivotal dose (Phase 3 trials, before submission)
~30% of drugs fail at this stage.
~70% succeed and proceed to submission for regulatory approval.
First submission to market (Regulatory approval stage)
7–10% of drugs fail and do not get approved.
~90–93% succeed and reach the market.
