InterMune Reports Top-Line Results From Phase 2b Study of Danoprevir (RG7227/ITMN-191) in Patients with Chronic Hepatitis C
BRISBANE, Calif., April 14, 2010 /PRNewswire via COMTEX/ --InterMune, Inc. (Nasdaq: ITMN) today announced top-line results from the planned Week 12 interim analysis of the Phase 2b randomized, partially-blind study evaluating the hepatitis C virus (HCV) protease inhibitor danoprevir (also known as RG7227 and ITMN-191), administered for 12 weeks in combination with PEGASYS(R) (pegylated interferon alfa-2a) and COPEGUS(R) (ribavirin), compared with placebo for the same duration plus PEGASYS and COPEGUS. The virologic response results are summarized in the following table:
Number (%) of Patients(1) with Virologic Response (<LOD)(2)
Background
therapy
Pegasys/
Copegus +300 mg +600 mg +900 mg +Placebo
---------- ------- ------- ------- --------
q8h q12h q12h (n=30)
--- ---- ---- ------
(n=67) (n=65) (n=50)
------ ------ ------
Week 4
(RVR(3)) 49 (73%) 56 (86%) 43 (86%) 2 (7%)
-------- -------- -------- -------- ------
Week 12 59 (88%) 58 (89%) 46 (92%) 13 (43%)
------- -------- -------- -------- --------
(cEVR(4))
---------
(1) Missing data counted as non-response
(2) Virologic Response = HCV RNA below the limit of detection
(<LOD) as measured by Roche COBAS TaqMan HCV Test (<15 IU/mL)
(3) RVR - Rapid Virologic Response
(4) cEVR - complete Early Virologic Response
Dan Welch, Chairman, Chief Executive Officer and President of InterMune, said, "The RVR and cEVR results reported today are among the very best reported by any DAA compound to date, reinforcing our view that danoprevir may potentially play a meaningful role in the treatment of HCV patients. With Roche, we are now focused on making the critical dose and regimen selection decision for future development plans for ritonavir-boosted danoprevir, an approach that appears to deliver strong efficacy and offer attractive advantages of dosing convenience and increased safety margin."
Frank Duff, M.D., Head of Roche's Clinical Development for Virology, said, "Future development of danoprevir is expected to be conducted in combination with ritonavir at total daily doses that are 10-25% of those examined in this study. The pharmacokinetics/pharmacodynamics and safety data from this large, well-controlled study, in addition to other data being collected, will be very helpful in our efforts to choose the optimal dose and regimen for the ritonavir-boosted danoprevir global development program, including the all-oral, direct-acting antiviral INFORM component of the program."
Safety and Tolerability
The analysis of the safety data is preliminary in nature and additional evaluation is ongoing. In the interim safety analysis, serious adverse events (SAEs) were generally balanced across all four treatment groups. The incidence of treatment-emergent Grade 4 (>10x ULN) ALT elevations was 0%, 1%, 6% and 0% in the 300 mg three-times daily, 600 mg twice daily, 900 mg twice daily and placebo groups, respectively. In the danoprevir treatment groups, these elevations occurred generally between weeks 6-8 or later and were reversible after discontinuation of danoprevir. Dosing of the 900 mg arm was stopped based on this safety signal. Treatment-emergent Grade 3 or Grade 4 neutropenia was reported in 24%, 25%, 31% and 16% of patients in the 300 mg three-times daily, 600 mg twice daily, 900 mg twice daily and placebo groups, respectively. The incidence of rash and anemia was comparable across all treatment groups, including the placebo group (SOC + placebo).
About the Study
The Phase 2b triple combination study, conducted at 45 sites globally, was designed to define the safety and efficacy profile of danoprevir for a treatment duration of 12 weeks as part of a total treatment duration of 24 or 48 weeks. The study was conducted by Roche as part of its collaboration with InterMune for the development of protease inhibitors. 232 patients were randomized to one of four treatment groups - three of which received a 12-week regimen of danoprevir at either 300 mg three times daily, 600 mg twice daily or 900 mg twice daily, in combination with PEGASYS and COPEGUS, followed by 12 or 36 weeks of therapy with PEGASYS and COPEGUS for a total of 24 or 48 weeks. The fourth group was a control arm receiving PEGASYS and COPEGUS for 48 weeks. In November of 2009, InterMune reported that due to a safety signal, dosing in the 900 mg group had been stopped. Patients already receiving treatment in this group continued on PEGASYS and COPEGUS. A total of 13 patients who were originally randomized to this group but had not received the study drug were later re-randomized to the other dose groups and are not included in the efficacy analysis. A total of 212 patients were included in the efficacy analysis population.
Similar virologic response was observed in all danoprevir treatment groups throughout the 12 weeks and after 12 weeks of treatment. Viral response of patients at the highest dose of 900 mg twice daily was not meaningfully different from that observed in patients who received 600 mg twice daily or 300 mg three times daily. Due to the 900 mg arm being terminated early, most of the patients in this 900 mg arm did not receive 12 weeks of triple therapy.
Other Studies with Danoprevir
InterMune announced in January 2010 that based upon promising preliminary results from a Phase 1b multiple-ascending-dose (MAD) study of ritonavir-boosted danoprevir, the full results of which are to be presented on April 15 at EASL, that the further development of danoprevir was expected to be in combination with low-dose ritonavir. The companies have amended the on-going Phase 1b MAD 15-day ritonavir-boosting study to evaluate 12 weeks of low doses of ritonavir-boosted danoprevir plus SOC, PEGASYS and COPEGUS, in prior SOC null responders. In addition, the companies plan to launch a Phase 2b study of ritonavir-boosted danoprevir plus SOC, PEGASYS and COPEGUS in late Q3 or early Q4 of 2010.
Regarding the direct-acting antiviral (DAA) program, the companies will evaluate the pharmacokinetics/pharmacodynamics and safety results of the Phase 2b study reported today, as well as those of the 4-week and amended 12-week Phase 1b MAD study of ritonavir-boosted danoprevir plus SOC, and possibly other data, to determine the dose and dosing regimen to take forward in the DAA program. The ritonavir-boosted DAA study to evaluate SVR may begin in the second half of 2010; the exact timing will be based on emerging data from the on-going studies.
About Danoprevir (RG7227/ITMN-191)
Danoprevir (also known as RG7227 and ITMN-191) is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity, and has produced multi-log(10) reductions in levels of HCV in chronic HCV patients, when administered for 14 days as monotherapy and when combined with PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin, USP). Danoprevir was safe and well-tolerated in these studies.
About InterMune
InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has an R&D portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes pirfenidone for which InterMune has completed a Phase 3 program in patients with IPF (CAPACITY) and a New Drug Application (NDA) has been accepted for Priority Review by the FDA and a Marketing Authorization Application (MAA) is under review by the European Medicines Agency (EMA). The hepatology portfolio includes the HCV protease inhibitor compound danoprevir (formerly RG7227) that entered Phase 2b in August 2009 and a second-generation HCV protease inhibitor research program. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.
Forward-Looking Statements
This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect InterMune's judgment and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines, the dates on which clinical data will be released and intended changes to certain of InterMune's clinical studies. All forward-looking statements and other information included in this press release are based on information available to InterMune as of the date hereof, and InterMune assumes no obligation to update any such forward-looking statements or information. InterMune's actual results could differ materially from those described in InterMune's forward-looking statements.
Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading "Risk Factors" in InterMune's most recent annual report on Form 10-K filed with the SEC on March 15, 2010 (the "Form 10-K") and other periodic reports filed with the SEC, including the following: (i) risks related to the long, expensive and uncertain clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues or delays in anticipated timing of the regulatory approval process; (ii) risks related to failure to achieve the clinical trial results required to commercialize our product candidates; and (iii) risks related to timely patient enrollment and retention in clinical trials. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the Form 10-K and InterMune's other periodic reports filed with the SEC, all of which are available via InterMune's web site at www.intermune.com.
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SOURCE InterMune, Inc.