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HCV Drug Update for Vertex, Roche, Idenix
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Vertex: New Drug Application planned for telaprevir in second half of 2010.....Proof-of-concept clinical trials planned for 2010 with novel combination regimens for hepatitis C....Upon completion of ongoing discussions with regulatory authorities, Vertex plans to initiate a combination trial of telaprevir and VX-222 in the first quarter of 2010. This trial is expected to evaluate SVR rates using multiple regimens of telaprevir/VX-222-based therapy in HCV patients.
Intermune/Pharmasset/Roche-Genentech: "The ritonavir-boosted regimen provided a more favorable pharmacokinetic profile than what has been previously observed for 900mg RG7227 administered twice-daily with SOC but without ritonavir. In view of these data, our plan is that the development of RG7227 will be in combination with ritonavir.......the company's plan is that the development of RG7227 will be in combination with low-dose ritonavir. Accordingly, the previously planned 24-week un-boosted part of the on-going Phase 2b triple combination study will now be replaced with a Phase 2b ritonavir-boosted study that is expected to begin in Q3 of 2010"
Idenix: Interim analysis of 50 mg cohort demonstrates potent HCV antiviral activity at 14 days for IDX184, a nucleotide polymerase inhibitor, in combination with PegIFN/Ribavirin. IDX375, a non-nucleoside polymerase inhibitor, exhibited favorable pharmacokinetic properties in a Phase I healthy volunteer study. Clinical Trial Application filed in December 2009 for IDX320, a next-generation protease inhibitor
InterMune Provides Program Update and 2010 Milestones for RG7227 (ITMN-191)
BRISBANE, Calif., Jan 11, 2010 /PRNewswire via COMTEX/ -- InterMune, Inc. (Nasdaq: ITMN) today provided an update (at JP Morgan Healthcare Conf) on its development program for protease inhibitor RG7227 (formerly referred to as ITMN-191) for the treatment of patients chronically infected with the hepatitis C virus (HCV). The company also reported guidance for the 2010 milestones and key events for RG7227.
Dan Welch, Chairman, Chief Executive Officer and President of InterMune, said, "Today we reported preliminary, top-line results from two cohorts of the Phase 1b, 15-day study of low-dose RG7227 co-administered with low-dose ritonavir and standard of care (SOC) in patients with chronic HCV. The majority of patients given ritonavir with 100mg RG7227 twice-daily or 200mg RG7227 once-daily were HCV RNA negative at the end of therapy. The ritonavir-boosted regimen provided a more favorable pharmacokinetic profile than what has been previously observed for 900mg RG7227 administered twice-daily with SOC but without ritonavir. In view of these data, our plan is that the development of RG7227 will be in combination with ritonavir."
Clinical Development Highlights and Recent Events
(RG7227)
- Enrollment began in August 2009 of the company's Phase 2b study of RG7227 in combination with PEGASYS(R) (pegylated interferon alfa-2a) and COPEGUS(R) (ribavirin), one of the options for the current standard of care (SOC) in HCV. The Phase 2b trial was designed to study both twice-daily (600mg and 900mg q12h) and three-times-daily regimens (300mg q8h) and both 12-week and 24-week treatment durations. On November 17, 2009, InterMune announced that three patients in the blinded 900mg q12h dosage cohort experienced an ACTG Grade 4 elevation in ALT levels, one of whom experienced an elevation of total bilirubin while also receiving concomitant allopurinol. After their review of un-blinded data from these patients, the study's independent Data Monitoring Committee (DMC) recommended that the 900mg q12h cohort be discontinued and that all other cohorts of the study continue. The companies accepted the DMC's recommendations. Enrollment of all remaining cohorts was completed in November of 2009.
- The company reported top-line results of a Phase 1 study of ritonavir-boosted RG7227 in healthy volunteers. Ritonavir is an antiviral compound commonly used at low, sub-therapeutic doses to enhance or "boost" the pharmacokinetic (PK) profiles of protease inhibitors. The results of this study demonstrated that the co- administration of low-dose ritonavir increased RG7227 concentration 12 hours post dose by 18 times, with the effect on Cmin being roughly 6 times and 3 times greater than the effect on Cmax and AUC, respectively. These results guided the selection of the substantially lower doses of RG7227 investigated in the Phase 1b MAD study in HCV patients.
- The company reported preliminary, top-line results of a Phase 1b multiple-ascending-dose (MAD) study that was initiated in September 2009 to evaluate low doses of once-daily and twice-daily RG7227 co-administered with low-dose ritonavir in combination with SOC for 15 days in treatment-naive HCV-infected patients. This study is examining the following three dosage regimens of RG7227, each with SOC and 100mg twice-daily ritonavir: o 100mg twice-daily RG7227 o 200mg once-daily RG7227 o 200mg twice-daily RG7227
Preliminary viral kinetic data from the first two cohorts of this study indicate that in the presence of SOC, the majority of patients achieved an undetectable level of HCV RNA after 15 days of treatment. The pharmacokinetic profile of ritonavir-boosted RG7227 was more favorable and less variable than that observed in previously reported studies conducted with much higher doses of un-boosted RG7227. No drug related serious adverse events have been reported to date. The companies hope to present the results from this study at a medical conference in the first half of 2010.
- Based upon these results, the company's plan is that the development of RG7227 will be in combination with low-dose ritonavir. Accordingly, the previously planned 24-week un-boosted part of the on-going Phase 2b triple combination study will now be replaced with a Phase 2b ritonavir-boosted study that is expected to begin in Q3 of 2010. As a result of not conducting Part B of the Phase 2b study, the company will un-blind the Part A 12-week cohorts earlier than originally planned and expects to provide both 4-week RVR data and 12-week EVR data late in the first quarter or early in the second quarter of 2010. In addition, the companies plan to amend the on-going Phase 1b MAD 15-day ritonavir boosting study to evaluate 12 weeks of RG7227 ritonavir-boosted therapy plus SOC.
2010 Key Project Guidance
The company provided the following guidance on the development timelines for RG7227.
Vertex Reviews 2010 Business Priorities to Support Goal of Becoming Fully-Capable Biopharmaceutical Company
-HCV: New Drug Application planned for telaprevir in second half of 2010, robust commercialization and launch preparedness activities ongoing-
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- Pipeline: Proof-of-concept clinical trials planned for 2010 with novel combination regimens for hepatitis C
- Financial: Vertex enters 2010 with approximately $1.3 billion in cash, cash equivalents & marketable securities and approximately $32 million in outstanding convertible debt-
SAN FRANCISCO, Jan 10, 2010 Today provided an update on key 2010 business priorities in conjunction with the 28th Annual J.P. Morgan Healthcare Conference in San Francisco. The company also discussed recent progress in its lead development programs in hepatitis C virus (HCV) infection and cystic fibrosis (CF) and outlined proof-of-concept clinical trials planned in other serious diseases for 2010.
"2010 will be a defining year for Vertex as we seek to evolve into a fully-capable biopharmaceutical company," said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex. "With ongoing Phase 3 programs in hepatitis C virus infection and cystic fibrosis, a broad pipeline of other emerging product candidate opportunities and a strong capital structure, we believe Vertex today has a unique opportunity to build a successful company focused on bringing multiple important therapies to patients. In 2010, we look forward to a series of defining events from late-stage and proof-of-concept clinical trials that may support further growth in the years ahead."
Mr. Emmens will deliver a live webcast presentation from the J.P. Morgan Healthcare Conference on Tuesday, January 12 at 2:30 p.m. PT (5:30 p.m. ET) where he will discuss recent clinical progress and provide an overview of Vertex's 2010 priorities. The webcast will be available on Vertex's website, www.vrtx.com.
"Phase 3 data for telaprevir, our lead drug candidate for the treatment of hepatitis C virus infection, will begin to emerge in the spring of 2010 to support the planned submission of a New Drug Application in the second half of this year. Our more than decade-long commitment to improving patient care in HCV is unwavering, and the Phase 3 program for telaprevir will remain our primary focus over the coming year. Importantly, we also recognize the need for continued innovation in the treatment of this disease, and we are preparing to initiate the first clinical trial combining telaprevir with the investigational HCV polymerase inhibitor VX-222 this quarter," stated Mr. Emmens.
"Beyond HCV, Vertex is conducting mid-stage and late-stage development of two novel compounds aimed at addressing, for the first time, the underlying mechanism of the orphan disease of cystic fibrosis. The VX-770 Phase 3 registration program is advancing rapidly, and we expect to obtain Phase 3 data for VX-770 early in 2011. Additionally, we also expect to obtain clinical data from a Phase 2 trial of VX-809 in the coming weeks that could potentially support the evaluation of VX-770 and VX-809 as part of a combination regimen in patients with the most common mutation of this disease.
"Supporting our vision to become a fully-capable biopharmaceutical company, Vertex is also planning multiple proof-of-concept clinical trials in other diseases, such as rheumatoid arthritis and epilepsy, and remains committed to maintaining investment into research to enable future product opportunities," concluded Mr. Emmens.
Phase 3 Registration Program for Telaprevir Nears Completion
Sustained viral response (SVR) data expected from Phase 3 ADVANCE trial in second quarter 2010 and from Phase 3 ILLUMINATE & REALIZE trials in third quarter 2010
- The ADVANCE, ILLUMINATE and REALIZE trials are evaluating telaprevir-based regimens as part of a global Phase 3 registration program in more than 2,200 genotype 1 treatment-naïve and treatment-failure patients with HCV infection.
- Vertex today announced that all patients in the ADVANCE and ILLUMINATE trials, which are evaluating telaprevir in treatment-naïve patients, have completed dosing of all study drugs, including pegylated-interferon (peg-IFN) and ribavirin (RBV), and are now in the post-treatment follow-up period to determine the number of patients who achieve SVR (defined as undetectable HCV RNA 24 weeks after the end of treatment). Vertex expects SVR data to become available from ADVANCE in the second quarter of 2010 and from ILLUMINATE in the third quarter of 2010.
- Vertex today also announced that all patients in the REALIZE trial, which is being conducted by Vertex's collaborator Tibotec and is evaluating telaprevir in patients who did not achieve SVR with a prior pegylated interferon-based treatment, are expected to complete dosing of all study drugs, including pegylated-interferon and ribavirin, by the end of January. Vertex expects SVR data to become available from REALIZE in the third quarter of 2010.
- Vertex plans to submit a New Drug Application (NDA) for telaprevir in the second half of 2010 for both treatment-naïve and treatment-failure patients.
Twice-daily dosing of telaprevir
In November 2009, Vertex announced SVR results from Study C208, an exploratory Phase 2, open-label clinical study of telaprevir. The study was conducted by Tibotec in Europe and evaluated a twice-daily (1125mg q12h) dosing schedule of telaprevir in combination with peg-IFN-alfa-2a (PEGASYS(R)) or peg-IFN-alfa-2b (PEGINTRON(R)) and RBV, as compared to the three-times-daily (750mg q8h) telaprevir dosing schedule used in telaprevir clinical trials to date. The C208 trial enrolled 161 treatment-naïve patients with genotype 1 HCV infection. The C208 data included the first SVR data for telaprevir-based regimens in treatment-naïve patients as part of a response-guided therapy trial design, similar to that being used in the ADVANCE and ILLUMINATE Phase 3 trials of telaprevir.
Vertex has submitted the Study C208 clinical data to the U.S. FDA, and Vertex and Tibotec have initiated discussions with regulatory authorities in the U.S. and E.U. regarding future development plans for telaprevir as part of an every-12-hour (q12h) dosing regimen.
Vertex collaborator completes dosing of telaprevir in Phase 3 trials in Japan
Vertex today announced that its collaborator, Mitsubishi Tanabe Pharma Corporation, has completed the dosing portion for telaprevir in three ongoing Phase 3 trials of telaprevir-based combination therapy in approximately 300 treatment-naïve and treatment-failure HCV patients in Japan.
New capabilities to support potential launch of telaprevir
Vertex continues to build its commercial infrastructure in preparation for the potential launch of telaprevir and has begun to develop and implement internal systems and processes to support the company's commercial operation and the potential future sale of telaprevir.
The company expects to establish key elements of its customer-facing operation in 2010, including the hiring of the sales management team to be charged with the implementation of a fully-functioning commercial sales force in 2011.
To inform launch preparedness activities, Vertex continues to conduct extensive HCV market research and is in discussions with key managed markets organizations and specialty pharmacies to generate additional insights on the HCV patient population, HCV patient care and flow, market communication strategies, and reimbursement processes for the HCV market.
Vertex has assembled a global supply chain network to support the potential launch of telaprevir and is currently manufacturing telaprevir at a commercial (metric ton) scale. The company has successfully completed all registration campaigns as well as validation campaigns of the active pharmaceutical ingredient (API) and is prepared to complete drug product validation in advance of the potential launch of telaprevir.
Potential Future Combination Regimens for HCV with Telaprevir and the HCV Polymerase Inhibitor VX-222
Initiation of first clinical trial of telaprevir combined with VX-222 planned for first quarter 2010
Vertex recently completed a multiple-dose Phase 1b viral kinetic study of the investigational oral HCV polymerase inhibitor VX-222. Interim results from the trial are consistent with the findings of a previously-conducted three-day viral kinetic study and support future clinical evaluation of VX-222, including the initiation of the first clinical trial of VX-222 in combination with telaprevir. Additional results from this Phase 1b study of VX-222 are planned for presentation at a medical meeting in 2010.
Upon completion of ongoing discussions with regulatory authorities, Vertex plans to initiate a combination trial of telaprevir and VX-222 in the first quarter of 2010. This trial is expected to evaluate SVR rates using multiple regimens of telaprevir/VX-222-based therapy in HCV patients.
Idenix Pharmaceuticals Highlights Progress in Three HCV Programs
- Interim analysis of 50 mg cohort demonstrates potent HCV antiviral activity at 14 days for IDX184, a nucleotide polymerase inhibitor, in combination with PegIFN/Ribavirin - IDX375, a non-nucleoside polymerase inhibitor, exhibited favorable pharmacokinetic properties in a Phase I healthy volunteer study - Clinical Trial Application filed in December 2009 for IDX320, a next-generation protease inhibitor
CAMBRIDGE, Mass., Jan 11, 2010 /PRNewswire via COMTEX/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced significant progress in three HCV programs. Idenix will provide a business update on these three HCV development programs and on its partnered programs during a presentation by Jean-Pierre Sommadossi, Ph.D., chairman and chief executive officer, to financial analysts and investors at the 28th Annual J.P. Morgan Healthcare Conference in San Francisco on Thursday, January 14 at 8:00 a.m. PST.
IDX184: Nucleotide HCV Polymerase Inhibitor
The phase II clinical trial, initiated in the fourth quarter of 2009, is a randomized, double-blind, placebo-controlled, sequential dose-escalation study evaluating the safety, tolerability, pharmacokinetics and antiviral activity of IDX184 in combination with pegylated interferon and ribavirin in treatment-naive HCV genotype 1-infected patients. Patients will receive a daily dose of IDX184 or placebo plus pegylated interferon and ribavirin for 14 days and then continue on pegylated interferon and ribavirin for an additional 14 days. Antiviral activity will be assessed at the 14-day and 28-day timepoints. Four dosing regimens of IDX184 ranging from 50 to 200 mg per day will be evaluated. In the 100 mg and 200 mg cohorts, QD and BID regimens will be compared. Each cohort includes 20 patients randomized 4:1, IDX184:placebo. This study is being conducted at multiple centers in the United States and Argentina.
Interim analysis of the first 10 patients randomized into the first cohort (50 mg QD):
Median ALT and AST levels, markers of liver injury, improved during treatment. There were no serious adverse events on treatment, no treatment discontinuations and laboratory profiles were comparable to standard PegIFN/Ribavirin treatment.
"We are very encouraged by these interim data for IDX184 combined with pegylated interferon and ribavirin and look forward to seeing additional data as the study progresses," said Douglas Mayers, M.D., Idenix's executive vice president and chief medical officer.
IDX375: Non-Nucleoside HCV Polymerase Inhibitor
A Phase I single ascending dose study evaluating the safety, tolerability and pharmacokinetics of IDX375 in healthy volunteers is ongoing. The first five cohorts (25 mg QD, 50 mg QD, 100 mg QD, 200 mg QD and 200 mg BID; 6 active:2 placebo) in this double-blind, placebo-controlled study have been completed. Data suggest favorable plasma exposure of IDX375 with a long elimination half-life of 32-40 hours demonstrating the potential for once- or twice-daily dosing in patients. IDX375 was generally safe and well tolerated. There were no significant lab abnormalities. The most common adverse event was mild diarrhea (3/30 subjects). Additional cohorts with higher single and multiple doses are planned.
IDX320: HCV Protease Inhibitor
A Clinical Trial Application for a new protease inhibitor clinical candidate, IDX320, was filed in December 2009. IDX320 is a non-covalent macrocyclic inhibitor with nanomolar potency, broad genotypic coverage and a favorable preclinical pharmacokinetic profile supporting the potential for once-daily dosing in man.
"We are pleased with these early data from our clinical programs and look forward to their continued advancement throughout the year," said Jean-Pierre Sommadossi, Ph.D., chairman and chief executive officer of Idenix. "In addition, we are excited about our new protease inhibitor clinical candidate, IDX320, and expect to begin a phase I clinical trial soon. With three promising clinical programs that span major HCV drug classes, Idenix is well positioned to play an important role in the transformation of the HCV treatment paradigm."
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