EARLY ON-TREATMENT RESPONSES DURING PEGYLATED INTERFERON PLUS RIBAVIRIN ARE INCREASED FOLLOWING 13 DAYS OF COMBINATION NUCLEOSIDE POLYMERASE

EARLY ON-TREATMENT RESPONSES DURING PEGYLATED INTERFERON PLUS RIBAVIRIN ARE INCREASED FOLLOWING 13 DAYS OF COMBINATION NUCLEOSIDE POLYMERASE (RG7128) AND PROTEASE (RG7227) INHIBITOR THERAPY (INFORM-1) - see attached full poster report of this interesting study



Reported by Jules Levin, EASL Apr 14-18 2010 Vienna Austria

“the profound viral suppression achieved with combination DAA therapy may reduce the high levels of interferon gamma–inducible protein (IP-10 or CXCL10) associated with chronic HCV infection, thereby reducing endogenous interferon activation levels.3 Thus, potent DAA combination regimens have the potential to not only block viral replication by arresting HCV RNA replication, but also to reconstitute innate host immune responses, thereby increasing the potential of long-term cure with finite DAA therapy…….These encouraging results suggest that, when given at optimal doses, a short course of dual combination therapy does enhance on-treatment response rates.”

E. Gane1, S. Roberts2, C. Stedman3, P. Angus4, B. Ritchie5, R. Elston6, D. Ipe6, P. Morcos6, L. Baher6, I. Najera6, T. Chu6, M. Mannino6, M. Berry7, W. Bradford8, M. Laughlin6, N. Shulman6, P. Smith6

1Auckland Clinical Studies, Auckland, New Zealand; 2Gastroenterology, The Alfred Hospital, Melbourne, VIC, Australia; 3Christchurch Clinical Studies, Christchurch, New Zealand; 4Gastroenterology, Austin Hospital, Melbourne, VIC, Australia; 5Gastroenterology, Royal Adelaide Hospital, Adelaide, SA, Australia; 6Roche Palo Alto LLC, Palo Alto, CA, USA; 7Pharmasset Inc., Princeton, NJ, USA; 8InterMune, Inc., Brisbane, CA, USA

Conclusions

The interferon-free dual oral combination regimen of RG7128/RG7227 produced rapid and profound suppression of HCV RNA replication through 13 days of dosing. These initial reductions in circulating HCV RNA prior to initiating treatment with peginterferon alfa-2a (40KD) plus ribavirin enhanced on-treatment virological responses at week 4 and 12 of treatment and end-of-treatment responses.

The 13-day combination regimen contributed to higher end of treatment virological response rates in groups B, C and D compared with the shorter and lower dose combination regimen in group A. The highest end-of-treatment response rate in treatment-naive individuals (100%) was achieved in patients treated with the highest dosage combination of RG7128/RG7227 (1000/900 mg bid). All patients achieved an RVR at week 4 of treatment with the SOC and were assigned to an abbreviated 24-week regimen. These encouraging results suggest that, when given at optimal doses, a short course of dual combination therapy does enhance on-treatment response rates.

Final SVR-24 results in all cohorts are awaited with great interest. Longer-term follow-up for SVR and larger studies will be needed to assess the clinical merits of combination DAA induction therapy prior to treatment with the SOC. However, such an approach is unlikely to benefit patients with contraindications to interferon, those intolerant of interferon, and individuals who have not responded to previous treatment with the SOC. In these populations, longer duration interferon-free combination DAA studies are planned.