Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

New molecular entities art always new novel mechanisms, sometimes improved old ones
Biologic licence applications - most commonly Mab (e
...
Mab IgE - Med restricted to
severely asthmatic patients [very expensive and only works in 50% of those patients])
Molecular entities are decreasing in terms of success rate
Biologic LAs are low but a steady rate
As there is an increase in understanding of biology there seems to be a decreased ability
to be be able to apply it to creating new medicines
As more targets are found its actually harder to find appropriate drugs
Do we really need new therapies?
There are needs and constraints - drives and drags
Drive - (promotion)
Unmet clinical need
Scientific progress
Commercial factors (less substantial in poorer countries)
Drag - (inhibits progress, mostly financial)
Healthcare providers
Needs the product to be realistically reimbursable (people to buy the drug)
Generics
Off patent --> appealing to healthcare providers as cheap
Rationing
For expensive treatments (e
...
Mab IgE)
Pricing policy
Asthma
A mature pharmaceutical market
ICS (Inhaled Corticosteroids) and bronchodilators: A stagnated clinical approach, or
simply the best that can ever be achieved?
Unmet needs certainly exist (can they be addressed)

COPD - more virgin territory in terms of new medicines
Growing pharmaceutical market wealth
Huge impact on healthcare resources
Asthma
400 million sufferers worldwide by 2025
High incidence in USA, UK, Australia, New Zealand
Growing incidence in BRICs (Brazil, Russia, India, China)
US $17bn pharmaceutical market in 2013
Predicted to be US $22bn by 2019
Huge amount of money to spend on medicines

Not everything is addressed in the treatment of asthma (as the above shows)

Current medicines for Asthma and COPD
β2-agonists (asthma and COPD)
Corticosteroids, ICS (asthma and COPD, but note a significant proportion of COPD
patients do not respond well to ICS)
Muscarinic antagonists (COPD > asthma)
Modern preference is to use these medicines in combination products

NICE Drug evaluation
Price of drugs vs QALY (Quality Adjusted Life Years)

Approaches in Development
Asthma
Various mAb therapies (eg anti-IL-5, anti-IL-13) targeting severe asthma
Small market harder to make and expensive to buy
Immunotherapy
Desensitisation to allergens (administrated in small doses until body tolerated it)
Effective for allergic rhinitis
New medicines for precedented mechanisms
COPD
LAMA/LABA combinations (Long Acting Muscarinic/Beta Agonists)
LAMA/LABA/ICS combinations
MABAs ( muscarinic antagonist/beta agonist activity in the same molecule)
Oral and Inhaled theophylline (to restore ICS responsiveness)
A strategic challenge: Stratified medicines v one drug for all
...
g
...

Poor DMPK = poorly absorbed
So usually subcutaneous injections

What is being treated where?
Affects preferred route of delivery
Inhaled drug delivery
Expensive to develop
Device adds to prescription cost
Multiple inhalers not popular with patients
Cannot be used with coloured drugs or those with unpleasant taste or effects on taste
perception
Can also change saliva colour
Not constrained by Lipinski rules
Oral drug delivery
Constrained by Lipinski rules
'Rule of 5' (limits type of molecule you can design)
Greater off-target vulnerabilities
Compounds need to have ultraclean toxicology
Inhaled Therapy
To non-experts an easy, fast, cheap option
In reality inhaled therapy is difficult
Oral DMPK hurdles become challenges to avoid irritancy, have acceptable physical
form, potency and solubility etc
However, Lipinski rules can sometimes be ignored
So, high PPB, FPM and poor bioavailability may be virtuous!
Potency must be high because device needs to contain many doses
For once daily dosing drugs and/or their effects must persist

---