Introduction (1)
Pharmaceutical medicine prof De Hoon
Introduction
Pharmaceutical medicine is the medical scientific discipline concerned with the discovery,
development, evaluation, registration, monitoring and medical aspects of the marketing of
medicines for the benefit of patients and the health of the community
- Medical discipline = specialty for medical doctors
- Started o> in the UK where the pharmaceutical industry was looking for medical doctors
who had su>icient knowledge about drug development
è Having a competent workforce to provide faster access to better medicines for patients
worldwide
In Europe
- Has become a medical specialty in many countries in Europe
- Discipline is available = Ireland, UK, Belgium and Switzerland
- Clininal pharmacology = close as a discipline, but more oriented towards the use of
drugs in people
è Not a rare discipline anymore, available in more countries
Is it important?
- Number 1 drug from Merck is going to give a return of 31 billion this year
└ It exceeds our Belgian deficit
└ Monoclonal antibody directed against a checkpoint inhibitor PD1
- Top 10 dominated by biologicals = mAbs and peptides
- Main areas = oncology, inflammation and obesity
è Pharmaceutical medicine is worthwhile to discuss because it represents a huge economic
activity
2024 European Medicines Agency’s (EMA) approvals
- Positive opinions on 114 submissions
- Of those submissions there were 46 new active substances
- And amongst those there were 6 PRIME drugs = priority medicines with a high need
- Also 15 Orphan medicines for Orphan diseases
- 1 ATMP = advanced therapy medicinal product
- 28 biosimilars = copies of existing biologicals & 17 generics
è Many new developments ongoing
,2024 Food and Drug Administration (FDA) approvals
- In 2024 a total of 50 new approvals were accepted
- Part of them being BLAs and part of them NMEs = new molecular entities
è Mostly in therapeutic areas neurology and oncology
Pharmaceutical classes
1. Majority were small molecules
2. Proteins
└ Of which the majority are mAb’s
└ Some bispecific = di>erent binding sites on both arms, so bifunctional
3. Oligonucleotides
,Pharmaceutical classes
First wave (1900s) = small molecules
- Screening of large numbers of compounds in high throughput systems
- Looked for 1 molecule with a high a>inity for 1 unique target
û O>-target e>ects = toxicity
└ Increase the dose à losing selectivity and binding with all kinds of targets
└ Results in side e>ects which are less predictable
- For example = the statins
└ Inhibit enzyme involved in endogenous cholesterol synthesis
└ Binds reversible with enzyme and prevents endogenous synthesis of cholesterol
└ If you give too much, you start having o>-target binding à toxicity of muscle
Second wave (1980s) = biologicals
- Designed by target = specifically designed to fit the target
- Fewer o>-target e>ects and if there is toxicity, it has rather to do with the binding to the
target itself or the nature of the pharmaceutical = allergic reaction & start producing anti-
drug antibodies
- For example = PCSK9 inhibitors alirocumab & evolocumab
Normally PCSK9 protein inhibitors
1) Hepatocyte expresses LDL 1) More LDL receptors expressed
receptor 2) Means improved ability to clear
2) Which can bind cholesterol cholesterol
3) Internalizes cholesterol 3) So a lower cholesterol level
è mAb’s influence the regulation of LDL receptor expression = more e>icient, 40% decrease in
cholesterol levels
Third wave (now) = genetic medicine ATMPs
- Advanced therapy medicinal products
- Can potentially change a disease such that it is no longer existing
- Treats/modulates the underlying cause
- Included siRNA, gene therapy…
- Often rare diseases or genetic cause
siRNA’s = Inclisiran decreases 60% of cholesterol
1) PCSK9 binds LDL receptor
2) Internalization of receptor & degradation of LDL receptor
3) Small piece of RNA can enter the hepatocyte
4) Once in the siRNA releases the single strand which is complementary to the normally
mRNA encoding PCSK9 à suppresses the expression of PCSK9
5) LDL receptor upregulation results in decrease of cholesterol levels again
, mRNA based vaccines
- For example = SARS-CoV-2 mRNA vaccines
- Inducing endogenous production of non-self proteins by administering synthetic mRNA
└ Give a piece of mRNA in order to express a protein = spike protein to mimic the
spike protein of the virus with the intention of developing Ab’s
è The endogenous expression of a viral antigen to which an immune response is induced
The drug life cycle
Drug life optimization: the three life periods
Early period = drug discovery & development
- First period
- Lasts 10-15 years so already at least half of the patent life has passed away
- From discovery to launch
- Costs money = investing
Middle period
- Once drug gets launched
- Gives return on investment
- The shorter the development period, the longer patent life in the middle period so the
longer time to get a return on your investment
Late phase
- Returnal investment starts to decline
- Less interest in the drug
- Drug might even disappear, no longer useful because there are better alternatives
Pharmaceutical medicine prof De Hoon
Introduction
Pharmaceutical medicine is the medical scientific discipline concerned with the discovery,
development, evaluation, registration, monitoring and medical aspects of the marketing of
medicines for the benefit of patients and the health of the community
- Medical discipline = specialty for medical doctors
- Started o> in the UK where the pharmaceutical industry was looking for medical doctors
who had su>icient knowledge about drug development
è Having a competent workforce to provide faster access to better medicines for patients
worldwide
In Europe
- Has become a medical specialty in many countries in Europe
- Discipline is available = Ireland, UK, Belgium and Switzerland
- Clininal pharmacology = close as a discipline, but more oriented towards the use of
drugs in people
è Not a rare discipline anymore, available in more countries
Is it important?
- Number 1 drug from Merck is going to give a return of 31 billion this year
└ It exceeds our Belgian deficit
└ Monoclonal antibody directed against a checkpoint inhibitor PD1
- Top 10 dominated by biologicals = mAbs and peptides
- Main areas = oncology, inflammation and obesity
è Pharmaceutical medicine is worthwhile to discuss because it represents a huge economic
activity
2024 European Medicines Agency’s (EMA) approvals
- Positive opinions on 114 submissions
- Of those submissions there were 46 new active substances
- And amongst those there were 6 PRIME drugs = priority medicines with a high need
- Also 15 Orphan medicines for Orphan diseases
- 1 ATMP = advanced therapy medicinal product
- 28 biosimilars = copies of existing biologicals & 17 generics
è Many new developments ongoing
,2024 Food and Drug Administration (FDA) approvals
- In 2024 a total of 50 new approvals were accepted
- Part of them being BLAs and part of them NMEs = new molecular entities
è Mostly in therapeutic areas neurology and oncology
Pharmaceutical classes
1. Majority were small molecules
2. Proteins
└ Of which the majority are mAb’s
└ Some bispecific = di>erent binding sites on both arms, so bifunctional
3. Oligonucleotides
,Pharmaceutical classes
First wave (1900s) = small molecules
- Screening of large numbers of compounds in high throughput systems
- Looked for 1 molecule with a high a>inity for 1 unique target
û O>-target e>ects = toxicity
└ Increase the dose à losing selectivity and binding with all kinds of targets
└ Results in side e>ects which are less predictable
- For example = the statins
└ Inhibit enzyme involved in endogenous cholesterol synthesis
└ Binds reversible with enzyme and prevents endogenous synthesis of cholesterol
└ If you give too much, you start having o>-target binding à toxicity of muscle
Second wave (1980s) = biologicals
- Designed by target = specifically designed to fit the target
- Fewer o>-target e>ects and if there is toxicity, it has rather to do with the binding to the
target itself or the nature of the pharmaceutical = allergic reaction & start producing anti-
drug antibodies
- For example = PCSK9 inhibitors alirocumab & evolocumab
Normally PCSK9 protein inhibitors
1) Hepatocyte expresses LDL 1) More LDL receptors expressed
receptor 2) Means improved ability to clear
2) Which can bind cholesterol cholesterol
3) Internalizes cholesterol 3) So a lower cholesterol level
è mAb’s influence the regulation of LDL receptor expression = more e>icient, 40% decrease in
cholesterol levels
Third wave (now) = genetic medicine ATMPs
- Advanced therapy medicinal products
- Can potentially change a disease such that it is no longer existing
- Treats/modulates the underlying cause
- Included siRNA, gene therapy…
- Often rare diseases or genetic cause
siRNA’s = Inclisiran decreases 60% of cholesterol
1) PCSK9 binds LDL receptor
2) Internalization of receptor & degradation of LDL receptor
3) Small piece of RNA can enter the hepatocyte
4) Once in the siRNA releases the single strand which is complementary to the normally
mRNA encoding PCSK9 à suppresses the expression of PCSK9
5) LDL receptor upregulation results in decrease of cholesterol levels again
, mRNA based vaccines
- For example = SARS-CoV-2 mRNA vaccines
- Inducing endogenous production of non-self proteins by administering synthetic mRNA
└ Give a piece of mRNA in order to express a protein = spike protein to mimic the
spike protein of the virus with the intention of developing Ab’s
è The endogenous expression of a viral antigen to which an immune response is induced
The drug life cycle
Drug life optimization: the three life periods
Early period = drug discovery & development
- First period
- Lasts 10-15 years so already at least half of the patent life has passed away
- From discovery to launch
- Costs money = investing
Middle period
- Once drug gets launched
- Gives return on investment
- The shorter the development period, the longer patent life in the middle period so the
longer time to get a return on your investment
Late phase
- Returnal investment starts to decline
- Less interest in the drug
- Drug might even disappear, no longer useful because there are better alternatives
