Embed Size (px)
Citation preview
13.10.2012
Innovative Biotechnologies for Human Healthcare
Prof. Theo DingermannInstitut für Pharmazeutische Biologie
BiozentrumMax-von Laue-Str. 9
60438 Frankfurt am [email protected]
Setting the SceneFrom Copying Towards Designing
Prof. Dr. Theodor Dingermann – Personalized Medicine
Mortality 1889 and 1992
1900: ca. 7 % of the 9 % living were healthy, i.e. 2 % were ill2000: ca. 30 % of the 58 % living are healthy, i.e. 28 % are ill
Mortality and Morbidity 1889 and 1992
Available drugs at the beginning of the 20th century:
Times of Pharmaceutical Revolutions...
• Acetylsalicylic (Aspirin®)• Aminopyrine (Pyramidon®)• Arsphenamine (Salvarsan®)• Barbital (Veronal®)• A Diphtheria Serum• Morphine• Procaine (Novocain®)• Strophanthine (Kombetin®)• Several Plant preparations
Modern drug development started in the mid 50th of the 20th
century!
Discovery of DNA as a universal coding concept of all biological systems in 1953.
Bob Weinberg (MIT)„With the discovery of the DNA double helix by Watson and Crick, biology became an exact science “.
Times of Biological Revolutions...
Discovery of DNA as a universal coding concept of all biological systems in 1953.
Cracking the genetic code in 1961 and the realization that this code is a universal code.
Times of Biological Revolutions...
Rekombinant Proteins
Genetic information unit = universally
understood in allbiological organisms
”Target"-organism
”Source"-organism
Rekombinant Proteins
Genetic information unit = universally
understood in allbiological organisms
Control units = extremely specific
”Target"-organism
”Source"-organism
Rekombinant Proteins
”Source"-organism
”Target"-organism
"genetic engineering"Control units Information unit
Geneticallymodified organism
(GMO) Extraction undpurification
Rekombinant Proteins
197 Biopharmaceuticals in the market by the end of 2011
mABs
27
Insulins Epoetin
100
50
0
32
8
Hormones
21
Enzymes
11
Clotting-factors
12
Interferons
9
Other
12
Vaccines
56
114
Indications for Biologicals
• Anemia• Angiogenesis Inhibition /
Macular Degeneration (AMD)• Antithrombotic• Asthma• Bacterial/viral Infections• Cancer• Chronic Inflammation • Coagulation Disorders• Diabetes• Fertility Disorder• Fractures• Growth Disorders• Immune Prophylaxis
• Impaired Wound Healing• Infarction/Stroke• Lysosomal Storage Diseases• Metabolic Disorders• Mucosal Inflammation• Multiple Sclerosis• Osteoporosis• Paroxysmal Nocturnal
Hemoglobinuria• Psoriasis• Respiratory Infections• Rheumatism• Sepsis• Transplantation
Rekombinant Drugs
At first glance it seems obvious:•recombinant drugs correspond to a natural, human molecule!
The second view shows:•A significant number of approved recombinant drugs does not correspond to a natural, human molecule!
• Some modifications are concessions to the technical feasibility – sometimes gaining significant clinical improvement (product generation 1a).
• Some molecules are in fact identical to human biomolecules (product generation 1b).
• Some intended modifications improve the clinical performance compared to the natural counterparts, partly because they take into account the significant differences between the physiological and the therapeutic delivery (2nd generation products).
• Some molecules are simply “newly invented" (3rd generation products).
Different „Product Generations"
Met-Somatropin (Protropin®)
H H
G
I E K D KR
M
Growth hormone
Somatropin
H H
G
I E K D KR
Growth hormone
Pegylated Somatropin
H H
G
I E K D KR
longer half-lifeModified growth hormone
Pegvisomant (Somavert®)
H H
G
I E K D KR
D D
NARST
KS
Growth hormone GH Receptor Antagonist
Anchor Innovation: „Genetically Modified Antibodies“
Anchor Innovation: „Genetically Modified Antibodies“
Anchor Innovation: „Genetically Modified Antibodies“
Anchor Innovation: „Genetically Modified Antibodies“
TNF Antagonists
Remicade®
(Infliximab)
TNF Antagonists
Remicade®
(Infliximab)
Humira®
(Adalimumab)
TNF Antagonists
Enbrel®(Etanercept)
Remicade®
(Infliximab)
Humira®
(Adalimumab)
TNF Antagonists
Enbrel®(Etanercept)
Remicade®
(Infliximab)
Humira®
(Adalimumab)Cimzia®
(Certolizumab)
TNF Antagonists
Enbrel®(Etanercept)
Remicade®
(Infliximab)
Humira®
(Adalimumab)Cimzia®
(Certolizumab)
Pegsunercept
Medical Progress is Expensive – Very Expensive ..
Medical Progress is Expensive – Very Expensive ..
INN Therapy costs Therapy costs
Human-Insuline per year ca. 420 €
Modified Insuline per year ca. 600 €
Cetuximab (Erbitux®) per month ca. 5.000 € initially,there after ca. 4.500 €
Trastuzumab (Herceptin®)(metastatic Mamma-CA)
per month ca. 3.400 € initially,thereafter ca. 2.800 €
Bevacizumab (Avastin®)(Mamma-CA)
per month 2 x 10 mg/kg ca. 6.600 €
Bevacizumab (Avastin®)(Colon-CA)
per month 2 x 5 mg/kg ca. 3.300 €2 x 10 mg/kg ca. 6.600 €
… Because Medical Progress Ignores Moore‘s Law!
Moore‘s Law
The number of transistors that can be placed inexpensively on anintegrated circuit doubles approximately every two years
Is the Medical Progress the “Quiet Killer” of the System?
medicalstandard
Additional costs
healthimprovement
worse and more expensive
better and cheaper
better and more expensive
cheaper and worse
What Makes a Medical Intervention Cost Effective?
economically determined cost effectiveness
MedizinischerStandard
Additional costs
worse and more expensive
better and cheaper
better and more expensive
cheaper and worse
rational prioritization on the basis of individual benefit
We Need a New Paradigm
Times of Biological Revolutions...
Decoding of the human genome in 2001: 3,2 x 109 genetic letters, ca. 25.000 genes
These properties result from genomic variations.They are inherited and are therefore stored in all cells of
an individual.
These properties result from genomic variations.They are inherited and are therefore stored in all cells of
an individual.
Some 7 Billion Genomes exist on Earth
inheritedfactors
acquired factors
The Sick Patient
The Sick Patient
Disease results from a combination of inherited factors and acquired factors (mutations)
The Sick Patient
any timefrom any cell
in case of a diseasefrom an affected cell
Medical progress has failed to be scalable so far, but moleculardiagnostics will change that.
Molecular Diagnostics Will Become a Key Technology
healthy
healthy
at risk
sick
healthy
at risk
efficacious
efficacious
partially efficacious
ineffective
efficacious
partially efficacious
tolerable
tolerable
problematic
toxic
tolerable
problematic
Classical diagnostics:• Detection of diseases
Molecular diagnostics:• Detection of diseases• Detection of disease risks• Prediction of
drug efficacydrug tolerability
Prof. Dr. Theodor Dingermann – Personalized Medicine
Diagnostics
Molecular diagnostics will provide the rationale for a personalized therapy and could help to make medical progress scalable.
Stratified Medicine = Efficacy & Effectiveness
Stratified Medicine = Efficacy & Effectiveness
Responder vs. Non-Responder
Antibodies Directed Against EGFR
Prof. Dr. Theodor Dingermann – Personalized Medicine
Antibodies Directed Against EGFR
ADRADR--ResponderResponder
ResponderResponder
NonNon--ResponderResponder
Optimal therapy for every individual patient
Solutions Through Innovative Technologies
From Copying Towards Designing
THANK YOU VERY MUCH
