Transcript Developing medicines for the future and why it is challenging

Developing medicines for the
future and why it is challenging
Angela Milne
Fundamentals of medicines
development
• Quality
• Safety
• Efficacy
Risk benefit assessment e.g. therapies
for hay fever vs those for advanced
cancer
Controls on medicines development
• Highly regulated process e.g. MHRA, EMEA,
FDA
• Stringent controls during drug development
• Assessment process prior to approval to
market
• Value based judgements prior to availability to
patients e.g. NICE, local formularies
Process of drug developmentprediscovery
• Select disease focus
• Commercial viability e.g. cancer, respiratory, cardiovascular
• Unmet medical need e.g. antibiotic resistance
• Expertise of scientists
• Gain understanding science of disease
Process of drug developmentdrug discovery
• Select target e.g. gene, protein and search for
molecules/compounds to alter disease
• Time frame 4 to 5 years
• 5,000-10,000 compounds to achieve one
approved medicine
• Cost £436 million
Process of drug developmentpreclinical
• Early safety and efficacy tests in
computational models, cells and animals
• Time frame one year
• 10 to 20 candidates to achieve one approved
medicine
• Cost £97 million
Process of drug developmentPhase 1 clinical trials
• Tested in human volunteers and patient
volunteers (20-100). No therapeutic benefit
• Time frame 1.5 years
• 5-10 candidates to achieve one approved
medicine
• Cost £177 million
Process of drug developmentPhase II
• Evaluation of candidates drug efficacy in
patients (100-500)
• Time frame 1.5 years
• 2 to 5 candidates to achieve one approved
medicine
• Cost £204 million
Process of drug developmentPhase III clinical trials
• Evaluation of candidate drug in patient
population for marketed indication (10005000)
• Generates efficacy, safety, and overall risk
benefit data
• Timeframe 2.5years
• 1-2 candidates to achieve one approved
medicine
• Cost 1.84 million
Licensing approval
• Information & results from all studies
compiled and submitted to regulatory
agencies e.g. EMEA, FDA
• Time frame 1.5 years
• One approved medicine (if only!)
• Cost £500,000
Drug development-total timeframe
and cost
• Average number of years to develop a
successful medicine- 12.5 years
• Average cost to research and develop a
successful medicine- £1.15 billion
Medicines available for patients
• Value & cost effectiveness assessments e.g.
NICE
• Local health budget availability
• Competitor products
Drug Development –it doesn’t stop
there!
• Original approval often given for limited
indication so repeat clinical trial process for
new indications e.g. for cancer drug usually
first approved for late stage cancer and then
researched for earlier stage cancers
• New formulations e.g. development of
sustained release formulations
• Development of improvements in
manufacturing process
Long term obligations
• Conduct of any additional studies required by
licensing authorities
• Long term monitoring of safetypharmacovigilance
• Meeting requirements of good manufacturing
practice
• Annual reporting requirements to regulatory
authorities
The future of medicines research
• Conventional pathway of drug development
has been successful for many years but the
hugely increasing cost of drug development
has not resulted in a similarly large increase in
the number of new medicines
• Additional techniques and approaches need to
be explored to expand the range of methods
to develop new medicines
New techniques and approaches
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Flexible drug development process
Increased collaboration
Value and outcomes evaluation in trial design
Personalised medicines
Personalised medicines
• Target treatments specifically to patient populations
most likely to respond
• Classify individuals into subpopulations that differ in
their susceptibility to a particular disease or their
response to a specific treatment
• Concentrate preventative or therapeutic interventions
on those most likely to benefit thus optimising patient
benefit, sparing side effects and expense of treating
those unlikely to benefit.
• Involves development and use of companion
diagnostics to achieve the best outcomes for the
patient
Targeted cancer therapy-hopes and
challenges
• Generally well tolerated and toxicity tends to be
less severe than with conventional cytotoxic
therapy
• Targeted therapy is different from other types of
therapy. Designed to target cells with specific
receptors for treatment
• Traditional therapies
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-Radiation therapy uses high energy rays to kill cells and or shrink tumours
-Chemotherapy is drugs that are used to destroy cells
-Hormonal therapy helps fight tumours that thrive on hormones like estrogns
by acting on hormone receptors on tumour cells or by decreasing the amount
of estrogen available to bind these receptors
Example of targeted therapy
• Herceptin is used for treatment of certain
Human epidermal growth factor receptor-2positive (HER2+) cancers e.g. breast cancer,
gastric cancer.
• HER2 testing is performed with the tumour
sample removed during surgery or using a
needle
How Herceptin may work
Targeted cancer therapy-hopes and
challenges
• Gefitininib is an epidermal growth factor receptor inhibitor. It was
originally tested in NSCLC patients many of whom did not have EGRF
positive NSCLC and did not show benefit over best supportive care. Seven
years after initial study subgroup analyses revealed benefit in patients
with activating mutations of EGRF and drug received licence for EGRFpositive patients.
• Crizotinib, an anaplastic lymphoma kinase inhibitor only tested in the 5%
of NSCLC was more effective than standard therapy in patients found to
express the target enzyme. It has been licensed for this indication
An integrated approach to the development of
personalised medicines
• Co-operation required between:
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Pharmaceutical industry
The diagnostics sector
Research funders
Regulators
Healthcare providers and policy makers
Health informatics programmes
Health economics
Discussion and questions
• How long have you got!