UIPS Utrecht Institute for Pharmaceutical Sciences Priority Medicines for Europe and the World: Cross-cutting themes Hubert G. Leufkens

UIPS Utrecht Institute for Pharmaceutical Sciences 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 patient- friendly 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. ‘Cross cutting themes’: drug delivery I

UIPS Utrecht Institute for Pharmaceutical Sciences 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. ‘Cross cutting themes’: drug delivery II

UIPS Utrecht Institute for Pharmaceutical Sciences 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. ‘Cross cutting themes’: elderly

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 million Europeans have a rare disease (prevalence < 5 out of ); a mosaic of 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.