Corporate Magazine 2012 - Boehringer Ingelheim

1viral entryrnareleasernatranslatedinto proteins[+] rna23DIRECT-ACTING ANTIVIRAL AGENTS (DAA)6[+] rna [–] rnaThe hepatitis C virus is a small enveloped virusthat contains a positive-strand RNA genomethat encodes a polyprotein that is processed byhost and viral proteases into 10 proteins thatare required for RNA virus replication.assemblyand releasernareplicationpolyproteinprocessingbi 207127ns5b polymeraseinhibitorfaldaprevirns3/4a polymeraseinhibitorBI 207127 –NS5B POLYMERASE INHIBITORThe HCV NS5B polymerase is anessential viral enzyme that catalysesvirus genome replication and hasattracted research interest sinceinhibition of polymerase activity offersan opportunity for therapeuticintervention. Boehringer Ingelheimhas led the optimisation of a class ofnon-nucleoside NS5B inhibitors exemplifiedby BI 207127.The NS5B inhibitors that have recentlyprogressed in clinical trials are expectedto become an important componentfor a more effective and bettertolerated anti-HCV regimens. A recentparadigm shift towards the developmentof interferon-sparing therapiesusing combinations of DAAs withcomplementary modes of action, suchas NS3 protease inhibitors in combinationwith NS5B inhibitors, is envisagedto provide efficacy with improvedsafety and tolerability whileminimising the emergence of resistantvirus.FALDAPREVIRNS3/4A PROTEASE INHIBITORThe NS3/4A protease is one of theessential viral proteins and pioneeringresearch at Boehringer Ingelheim todiscover inhibitors of this viral enzyme.It led to the first clinical trialwith the NS3 protease inhibitor BILN2061 (ciluprevir) that clinically validatedthe NS3 protease as an attractivedirect antiviral target.Potent second wave NS3 protease inhibitorssuch as Boehringer Ingelheim’sfaldaprevir, currently in phase 3 clinicaltrials in combination with PegIFN/RBV,may be expected to provide simplifieddosing regimens and a further improvementin treatment options.FDA fast-track designationThe US Food and Drug Administration(FDA) granted fast-track designation forthe interferon-based development programmesfor faldaprevir in combinationwith PegIFN/RBV for genotype 1patients and the interferon-free regimenof faldaprevir and BI 207127 plusribavirin/RBV.This process is selected by the authoritywhen drugs to treat serious diseaseswith high unmet medical need shouldbe developed. Patients with HCVshould receive important new medicationsas in an attempt to get importantnew drugs to people with HCV as soonas possible.54 Boehringer Ingelheim annual report 2012