CHAPTER 1: INTRODUCTION Steven Van Cruchten
introduction
module 1: clinical research and laboratory techniques
module 2: preclinical drug research
module 3: clinical drug research
on the exam: 10/20 points on interpreting a drug insert. We practice that in a seminar
(obligatory) of half a day. Written examination, only know the powerpoint slides, the
book is for background.
general aspects
= drug development is a lengthy phase, it takes a long time (often 12 years) and costs a
lot of money.. There are a couple of phases in drug discovery and development
molecule —----> drug
- chemicals: small molecules like aspirin
● easy to take in because it can be administered orally
- natural products: complex molecules
● we will not really address this
- biologicals/biopharmaceuticals: large and complex molecules like insulin, EPO..
● orally not possible here
● often other ways of administration
● animal models are not sufficient for these biologicals, toxicity and stuff is
different
some facts and figures of R&D in the pharmaceutical industry
some facts
- companies are investing more and more money in drugs development and
research, but the FDA approves less and less drug
- A lot of the new drug approval = against cancer
- full cost of bringing a drug on the market is on the rise → 1 billion dollars.
major disease areas
- cardiovascular diseases (biggest chunk)
- cancer (2nd biggest chunk)
- respiratory system (COPD, muco..)
- digestive system..
clinical trials
- clinical trials are the most expensive of the drug development
1
, - often done on male students because they can’t risking infertility of women
and/or death or sickness of an unborn child
- the risk of having problems with male infertility is less then with female volunteers
- often low doses are admitted, dose is not a high concentration⇒ this phase is
about checking the pharmacokinetics ⇒ is the drug absorbed, what is the
concentration in plasma…
- healthcare spending in relation to age: our population gets older, the older people
ned more medicines because they have more diseases ⇒ cost more money
development costs and revenue cycle
- total cost for one new marketed drug: 0.8-1,5 billion dollars
- largely depends on therapeutic area you are in
- 70% R&D costs + 30% direct costs
!! almost no investment in neglected diseases or orphan diseases (=rare, neglected
diseases). Governments or foundations like Bill Gates foundation have to step in to
finance this, because it often is not a profitable cause for the pharmaceutical company.
- first you have to invest,
you don’t make any
money
- but the investment is
almost nothing compared
to the money you will
make after
- the money drops again
when the patent is expired
and because there is
generic competition →
other, generic companies
will ‘copy’ this drug and sell it for less, that also causes a drop
sales per region
- US is the frontrunner for sales, because you can get drugs over the counter
- then europa
- then te other countries
blockbuster drug
= when you have a sale of more than 1 billion dollars per year, for example Humira (20
million dollars per year!) These drugs often come from large pharmaceutical companies
- 70% of the industry’s profits come from 20% of the marketed drugs
- this is also the driving force behind mergers
- pharmaceutical industry is a core sector for Europe
- but competitiveness is declining
2
, - humira: anti-inflammatory that works against arthritis (=abalumimab)
new drug launches
- are often biopharmaceuticals
- gene therapy is more and more popular
- competition in pharmaceutical market
● if you already have competition in the market, you will have less income
● the competition is increasing!
challenges for pharma industry
1. the generic competition!!
- Shrinking period of market exclusivity
- Increased competition between pharmaceutical companies
2. price containment: governments really want to lower the price setting
3. poor product differentiation: a drug should be better then the one already on the
market, otherwise physicians will not prescribe this
failure rates in drug development
= failures are often in the preclinical
development, but also in phase 1 or phase 2
clinical trial when for example you don’t
reach the exposure or the drug does not
work. In phase 3 and the phases after you
really can’t have that it doesn't work
anymore because you already spend all
your money, but it can happen because it
doesn’t get approved or smt. Bad
pharmacokinetics is a good reason not the
continue (30%), or lack of efficiency.
biotechnology-derived medicines
= huge area of new therapeutic medicines, you try to target a specific sequence of rna
or proteins (less toxicity!)
- mainly monoclonal antibodies and vaccines
- rna-based therapeutics: you inhibit the disease proteins, oligos, micro-rna’s…
- on the rise!
major pharmaceutical companies
= Roche, Novartis, Pfizer, Merck, J&J, Sanofi, Abbvie, gsk… They often have a lot of
therapeutic areas like cardiovascular, urology, oncology.. When there is a problem in 1
area, the other can make up for the loss of money
1. gsk:
- first female CO
3
, - 117 countries, headquarter: UK
- focusing on over-the-counter medicines (OTC) like toothpaste or zovirax,
also focus on vaccines, twinrix, retrovir
2. pfizer:
- Locations: > 150 countries, headquarter: New York, USA
- also has a veterinarian area (zoetis)
- zoloft, viagra..
3. Johnson & Johnson:
- Locations: > 55 countries, headquarter: New Brunswick, New Jersey, USA
- imodium, perdolan, hand cream… (OTC)
- but also medical devices and diagnostics, lik blood glucose meter or stents
4. Sanofi:
- Locations: > 100 countries and > 100,000 employees
- headquarter: Paris, France
- Therapeutic areas: Cardiovascular, thrombosis, metabolic disorders,
oncology, central nervous system, internal medicine and vaccines
- Ablynx: bought by sanofi in 2018
5. novartis
- Locations: > 140 countries and > 100,000 employees
- Headquarter: Basel, Switzerland
- Therapeutic areas: Pharmaceuticals: cardiovascular & metabolism,
oncology & hematology, neuroscience, respiratory, infectious diseases and
internal medicine ⇒ Sandoz for generics
6. Astrazeneca:
- Locations: > 140 countries, Headquarter: London, UK
- Therapeutic areas: Pharmaceuticals: cardiovascular, gastrointestinal,
oncology, neuroscience, respiratory, infectious diseases and inflammation
- also vaccines, is a merger between a swiss and a Uk company, sometimes
hard to make to two work together
7. Merck
- Locations: 120 countries
- Headquarter: Whitehouse Station, New Jersey, USA
- Therapeutic areas: Pharmaceuticals: cardiovascular, gastrointestinal,
oncology, neuroscience, respiratory, infectious diseases and inflammation
8. Roche
- Locations: 150 countries
- Headquarter: Basel, Switzerland
- Therapeutic areas: Pharmaceuticals: Cardiovascular & metabolism,
oncology, virology, neuroscience, respiratory
- Diagnostics
9. Briol-Myers squibb
- Locations: mainly USA, but also other regions, incl. Belgium Ø Headquarter:
New York City, USA
4
