Download Cross Cutting Themes (Chapter 7)

Priority Medicines for Europe and
the World:
Cross-cutting themes
Hubert G. Leufkens
UIPS
Utrecht Institute for
Pharmaceutical Sciences
‘Cross cutting themes’: drug delivery I
• There is an array of existing evidence based, but very
often off-patent, technologies that is heavily ‘under-used’.
• Such technologies could be used to improve the patientfriendly performance of a number of existing drugs in for
instance FDCs (‘translational research’).
• But also in the context of the use of medicines in
paediatrics and geriatrics, and other areas where
individualized time-dosing of medicines is required.
• Safety concerns drive increasingly the need for targeting
potent, but very toxic, medicines (e.g. cytostatics,
antivirals and certain antifungals) to their site of action in
the body, instead of exposing the whole body to the drug.
UIPS
Utrecht Institute for
Pharmaceutical Sciences
‘Cross cutting themes’: drug delivery II
• The advent of new biotech derived protein/DNA based
medicines call for better delivery technologies.
• New stabilization concepts (e.g. heat resistant insuline
of oxytocin) and other ‘all-weather’ drug delivery
systems are highly desired.
• Moreover, most current protein/DNA based medicines
need the parenteral route (i.e. injection, infusion) to be
administered to the patient.
• Many therapies based on 'biologicals', including gene
therapies, vaccines, need targeted delivery systems
specific sites on the cell, inside the cell or inside the cell
nucleus.
UIPS
Utrecht Institute for
Pharmaceutical Sciences
‘Cross cutting themes’: elderly
• Epidemiology/demographics teaches us that in 2020 one
out of three of us is 60 years or over.
• Changes in pharmacokinetics and dynamics; inappropriate
dosing and drug delivery.
• High rates of co-morbidities and polypharmacy, increased
incidence of drug-drug interactions, adverse drug
reactions; most ADRs are preventable!
• Lack of data on long-term outcomes of therapies used for
extensive periods of time (>5-10 years).
• Underuse of proven (preventive) medicines.
• Still, although many improvements have been made, lack
of knowledge due to exclusion of elderly from clinical trials.
UIPS
Utrecht Institute for
Pharmaceutical Sciences
‘Cross cutting themes’: paediatrics
• Paediatric clinical guidance cannot be linearly abstracted
from adult data (unlicensed and off-label use!); existing
(adult) medicines do not provide a satisfactory array of
therapeutic options.
• Some paediatric morbidities are specific to childhood (e.g.
neonatal respiratory problems, paediatric cancers); other
conditions ask for more specific drug formulations and/or
dosing schemes.
• Certain childhood morbidities are very often 'early
signatures' for severe and chronic adult diseases (e.g.
wheezing/childhood asthma, obesity, psychiatric).
• Methodological and ethical issues in the context of
paediatric trials.
UIPS
Utrecht Institute for
Pharmaceutical Sciences
‘Cross cutting themes’: women
• Although women are the most frequent users of
medicines, little is known about many aspects of women’s
interaction with drug therapy.
• Many of such interactions are related to hormones (e.g.
contraceptives, infertility treatment, postmenopausal
disorders, osteoporosis); large numbers of women
affected; long-term effects (10-20 years) not well known.
• Underfunded and poorly developed risk management
systems on birth defects: great need for data on birth
effects, susceptible exposures and classification systems.
• Methodological and ethical issues related to participation
of women in clinical trials.
UIPS
Utrecht Institute for
Pharmaceutical Sciences
‘Cross cutting themes’: orphan diseases
• 25-30 million Europeans have a rare disease (prevalence
< 5 out of 10.000); a mosaic of 5000-8000 diseases; 80%
genetic origin; 30% present at children’s age.
• Regulatory framework has improved significantly.
• Cause of the disease is very often unknown, diagnosis not
clear, no insight in natural history of disease.
• Although genomic and proteomic sciences provide
increasingly clues for diagnosis/treatment of orphan
diseases there is a serious gap in clinical evaluation.
• Long-term epidemiology data on use of orphan drugs,
patient safety and effectiveness are lacking.
• Issues related to access to available orphan drugs.
UIPS
Utrecht Institute for
Pharmaceutical Sciences