BI 207127, a novel HCV RNA polymerase inhibitor

Safety, pharmacokinetics and antiviral effect of BI 207127, a novel HCV RNA polymerase inhibitor, after 5 days’ oral treatment in patients with chronic hepatitis C-- attached is full poster report with graphs/table

Reported by Jules Levin EASL Copenhagen, April 23-26 2009

Boerhinger Ingelheim reported on their HCV protease inhibitor at AASLD Nov 2008 where they reported the drug showed about 4 log reductions viral load in early studies. Phase II is ongoing and results from that study should be reported soon. They say in this poster in conclusions below they are planning a combination study of these 2 oral HCV drugs. The future of HCV therapy is multiple oral drugs in combination with peg/rbv until a company can establish that a regimen of oral drugs alone will produce an SVR without peg/RBV, which all the companies are planning to study. I expect 2 oral drugs plus peg/RBV should produce 75% or higher SVR rates in treatment-naives an a little owe in African-Americans and prior null and nonresponders.

Dominique Larrey1, Yves Benhamou2, Ansgar W Lohse3, Christian Trepo4, Christian Mölleken5, Jean-Pierre Bronowicki6, Keikawus Arastéh7, Marc Bourlière8, Markus Heim9, Jaime Enríquez10, Andreas Erhardt11,Jean-Pierre Zarski12, Reiner Wiest13, Tilman Gerlach14, Heiner Wedemeyer15, Thomas Berg16, Jerry Stern17, Katherine Wu17, Nasri Abdallah18, Gerhard Nehmiz19, Wulf Boecher19, Jürgen Steffgen19 for the BI 207127 study group

1INSERM 632-CIC Hôpital Saint Eloi, Montpellier, 2Hôpital La Pitié Salpétrière Paris, 3Universitätsklinikum Hamburg-Eppendorf Hamburg, 4Hôpital Hotel Dieu Lyon, 5Universitätsklinik Bochum, 6Hôpital de Brabois Nancy, 7Epimed GmbH Berlin, 8Hôpital Saint Joseph Marseille, 9Universitätsspital Basel, 10Hospital de la Santa Creu I Sant Pau Barcelona,11Universitätsklinikum Düsseldorf, 12Hôpital Michalon Grenoble, 13Klinikum der Universität Regensburg, 14Kantonsspital St. Gallen, 15Medizinische Hochschule Hannover, 16Charité Berlin Campus Virchow-Klinikum Berlin; Boehringer Ingelheim 17Ridgefield CT, 18Reims and 19Biberach

AUTHOR CONCLUSIONS

BI 207127 is a potent inhibitor of viral replication in monotherapy, causing a steep decline of VL at 800 mg q8h in the first 24 hours (5/9 patients with >4 log10 VL reduction at Day 5, no VL breakthroughs)

BI 207127 was safe and overall well tolerated; the only drug-related SAE, a moderate erythema, was managed effectively. One mild transient rash did not require BI207127 dose reduction or discontinuation

The results from the present study demonstrate, that further clinical development of this promising direct antiviral in combination therapy with PegIFN/RBVis warranted

A 4-week combination study will initiate in late Q2/2009