Drugs and Drug Development Stages
Drugs and Drug Development Stages
Drugs and Drug Development Stages
Chemistry
Nayang A. Kgakatsi, PhD
Dept. of Pharmacy
Drugs may be taken for short times (acute) or over long periods (chronic)
or may be taken to avoid or blunt a disease process (prophylactic).
For example:
Peptic ulcers are now almost unheard of due to introduction of safe
controllers of stomach acid secretion, cytoprotective agents and
novel triple therapies using antibiotics.
Activity 1
Give examples on how drugs improved the quality of life
Answers!
Heart disease is controlled and quality life prolonged for millions due
to use of effective blood pressure control medicines and cholesterol
lowering agents (statins).
Hepatitis C infection can now be cured quickly and with few side
effects with a new generation of anti-viral super-drugs
Making drugs is hard. But worth it!
Some notable quotes
“ We try to remember that medicine is for the patient. We try to never forget that medicine is for the people. It is
not for the profits. The profits will follow, and If we have remembered that, they have never failed to appear”
- George Merck, Medical College of Virginia, December 1950
“I never found it easy. People say I was lucky twice but I resent that. We stuck with [cimetidine] for four
years with no progress until we eventually succeeded. It was not luck, it was bloody hard work.”
[Rejecting that drug discovery was easier in the past.]
-Sir James Black- quoted in Financial Times 1 Feb, 2009
‘It’s harder to bring a new drug to market than to put a man on the moon’ Attributed to Chris Hall
accepting the Heroes of Chemistry Award from the ASC on behalf of Merck inventors of the AIDs drug
Isentress, ACS National Meeting 8 Sep. 2013
UNMET MEDICAL
NEEDS
Learning goal
Determine attributes of unmet medical needs
Assess diseases as unmet needs
Vocabulary
unmet medical need, orphan disease, rare disease, & neglected tropical
disease
Unmet Medical Needs
1. Alzheimer's disease
Beyond the early stages of the disease, Alzheimer's has no effective
drugs. Alzheimer's disease is a huge unmet medical need.
Through identifying unmet needs, a drug company increases the chance that
any new drug will provide both financial gain to the company and a health care
benefit to patients.
Conclusion
We have now learned the definition of an unmet medical need...
that is, a disease that cannot be satisfactorily treated with current
therapies or drugs.
As of June 3, 2022, there were 1,521 drugs and vaccines in development targeting the coronavirus disease (COVID-19). American biotech company
Moderna was the second ranked company worldwide with 12 drugs/vaccines in development targeting COVID-19.
Revenue of the worldwide pharmaceutical
market continues to grow
Total global pharmaceutical research and development (R&D)
spending also growing (2012 to 2026)
Global pharmaceutical sales from 2017 to 2021, by
region (US is by far largest)
https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual- report-2021/pdf/AstraZeneca_AR_2021.pdf
And most new drugs are first approved in the US
TARGETS, ASSAYS, &
LEADS
Learning goal
How to prioritize a drug target
Describe role of an assay
Summarize lead selection
Vocabulary
Drug target, downstream, druggable, target-based drug discovery, assay,
potency, efficacy, screening, hit, & lead
Once we have identified our unmet medical need, it's now time to begin
the drug discovery process.
So, this beginning starts with unraveling the biological pathways that are
associated with the disease.
Biological pathways are managed by proteins for the most part --
enzymes and receptors.
And in theory, if you can block the action of an enzyme or receptor along
a pathway, you can potentially have a therapeutic effect on a disease.
We have a hypothetical set of enzymes and
receptors -- potential drug targets,
associated with different responses.
Receptor A pain response
Our interest is on inflammation
response Enzyme B Enzyme C
inflammation
As we look at this pathway, we have five response
Vocabulary
Lead optimization, pharmacokinetics, animal
model, toxicology & good laboratory practice
We'll focus on the different factors that are relevant for improving or
optimizing the activity of a lead, and then we'll discuss how animal
studies are so important for predicting the activity that a molecule
may show in humans.
Once a lead has been selected, the medicinal chemistry team will
begin to modify the structure of that lead molecule in order to
improve its properties.
What properties will be optimized?
Four properties for lead optimization
Potency
Efficacy
Toxicity
Pharmacokinetics
Potency
It indicates the amount or dosage of a drug
needed to produce a specific effect.
Hits and leads are fairly potent, meaning they affect
the drug at a somewhat low concentration.
Toxicity
Potential toxic interactions of a lead will be
minimized.
So the goal in lead optimization is to
minimize toxicity.
Pharmacokinetics
Pharmacokinetics addresses how a drug
flows through the body.
So a drug has to enter the body and leave
the body, and pharmacokinetics addresses
this idea.
One of the outcomes of pharmacokinetics
is something like the drug's half-life.
Vocabulary
Investigational new drug, clinical trials, health volunteer, adverse drug reaction,
patient, pivotal trial, standard of care, new drug application, new molecular
entity. & new chemical entity
We'll learn about what happens at each stage of the different
clinical trials and how all the clinical trials collectively help
determine the safety and effectiveness of a potential drug.
To test a lead in humans, a drug company must submit an
investigational new drug application, or IND, with the Food
and Drug Administration, the FDA.
Phase 1.
Phase 1 trials involve 25 to 75 health
volunteers
Phase 1 test subjects do not have the
disease of interest.
Phase 1 trials determine safe dosing levels.
Researchers also learn about what type of side effects, more
properly called adverse drug reactions, or ADRs, the patients
might show during later trials.