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 development-prediscovery

• 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 development-drug 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 development-preclinical

• 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 development-Phase 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 development-Phase 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 development-Phase III clinical trials

• Evaluation of candidate drug in patient population for marketed indication (1000-5000)

• 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 safety- pharmacovigilance

• 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

• 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• -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-2-positive (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

An integrated approach to the development of personalised medicines

• Co-operation required between:• 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!