Venue: Restaurant Skovlyst, Skovlystvej 2, 3500 Værløse
Time: 10:30 - 16:00
DDI – Assessment of Drug-Drug Interaction potential
The issue of DDI guidance(s) by worldwide Regulatory authorities (FDA/EMA/PMDA) during 2012/13 and more recently late 2017 by the FDA now form a solid framework for the assessment of small molecule drug-drug interactions (DDI), an increasingly important area of drug development. This presentation will review the various aspects of modern DDI assessment including the recent FDA DDI guidance issued in October 2017 that are currently recommended worldwide, and the information regulators will want to see, regarding assessing interactions with CYP and UGT enzymes and drug transporters. We will also discuss where the gaps are and what further guidance we can expect.
This presentation will review areas of significant risk for new drugs in development – delay at NDA, non-approval and post-market withdrawal. A frequent cause of delay at NDA is due to differences between animal and human drug metabolism and the identification of potentially ‘disproportionate’ circulating human metabolites. A major cause of drug non-approval (outside of lack of efficacy) is having a high DDI liability as a victim drug (that is, Fm/Ft approaches 1). The number one cause of safety-related drug withdrawal (post-market) is for Drug Induced Liver Injury (DILI). The decision to develop a lead compound is a critical stage of drug development and it is desirable to try and promote a compound that does not carry a metabolic liability that makes it susceptible to these risks. De-risking is the intelligent design and application of highly focussed modern in vitro programmes (DDI, MIST and DILI assessment) which can efficiently highlight whether the development of a new drug may be hindered by having liability in these major risk areas. A drug that is low or negative for DDI, MIST and DILI is considerably de-risked and in addition to a more simplified clinical development path, de-risking provides confidence to invest and also markedly increases the value of your molecule.