Biotech Values

[DewDiligence]

(IMTN) Roche Starts Phase-1b Trial of Ritonavir-Boosted ITMN-191

[I previously thought ITMN itself might conduct this trial (which would have suggested to me that Roche was not fully on-board with the use of ritonavir), but this is clearly not the case. The purpose of using ritonavir is to enable ITMN-191 to be dosed BID or qD rather than TID (although I think qD dosing is a stretch). A secondary benefit, not specifically cited in this PR, is that ritonavir may facilitate co-formulation of ITMN-191 with other oral meds by allowing ITMN-191 to be dosed efficaciously at a lower level, decreasing the physical size of the ITMN-191 + ritonavir combination relative to the size of standalone ITMN-191 with comparable efficacy. Ritonavir is sold by ABT under the brand name, Norvir, and is the subject of pending litigation (#msg-31102936).]

http://finance.yahoo.com/news/InterMune-Announces-prnews-4008313309.html/print?x=0

›Tuesday September 29, 2009, 7:00 am EDT

BRISBANE, Calif., Sept. 29 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN ) today announced that its partner Roche has begun dosing in a Phase 1b multiple ascending dose (MAD) study of ITMN-191 (RG7227) boosted by low-dose ritonavir in patients chronically infected with hepatitis C virus (HCV) genotype-1.

Ritonavir boosting is an option to enhance and improve pharmacokinetic profiles of protease inhibitors. It is well established in the treatment of HIV where it leads to more convenient dosing, reduced resistance development and high efficacy. Not all HCV protease inhibitors are suitable for ritonavir boosting. However, as InterMune announced on August 6, 2009, ITMN-191 showed high promise in a Phase 1 single ascending dose (SAD) study in healthy volunteers. Important PK parameters showed marked improvement and significant increases in AUC and drug concentrations were observed. There were no remarkable safety findings.

"We and our partner Roche are very pleased by the performance of ITMN-191 in twice-daily regimens when un-boosted with ritonavir," said Dan Welch, Chairman, Chief Executive Officer and President of InterMune. "However, if results of ritonavir boosting of ITMN-191 in human volunteers are replicated in this study of HCV patients, the approach could lead to achieving more sustained exposures with lower twice-daily doses of ITMN-191 or perhaps allow once-daily administration. Either of these two possibilities could provide patients a regimen with more convenient administration and with the clinical advantages associated with sustained drug exposure."

The objective of the MAD study is to determine the pharmacokinetic (PK), viral kinetic and safety profiles of ascending doses of once-daily and twice-daily ITMN-191 co-administered with low doses of ritonavir and standard dose Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin) in HCV-infected patients and for 14 days. On August 6, the company announced results of a Phase 1 study of ITMN-191 co-administered with low dose ritonavir in healthy volunteers.

About ITMN-191/RG7227

ITMN-191/RG7227 is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity currently in Phase 2b development. The compound is being developed in collaboration with Roche. ITMN-191 has produced multi-log10 reductions in HCV levels in chronic HCV patients, when administered for 14 days as monotherapy. When ITMN-191 was combined with Pegasys and Copegus, or the NS5B polymerase in Phase 1b studies, it reduced HCV viral loads below the limit of quantification in the majority of study-treated patients. The safety and antiviral activity of ITMN-191 is also under clinical investigation in combination with the NS5B nucleoside inhibitor RG7128 in the INFORM clinical development program. To date, ITMN-191 has been safe and well tolerated in these studies.‹