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Vertex, InterMune, and Idenix Present Hepatitis C Drug Development Updates at Investor Conference

SUMMARY: At the 28th Annual J.P. Morgan Healthcare Conference, which took place January 11-14 in San Francisco, pharmaceutical and biotechnology companies presented updated information about their clinical development portfolios to potential investors. Among the presenters were 3 companies with directly targeted oral HCV drugs in the pipeline: Vertex Pharmaceuticals (telaprevir, VX-222), InterMune Inc. (RG7227 [formerly known as ITMN-191], RG7128), and Idenix Pharmaceuticals (IDX184, IDX375, IDX320).

Below are edited excerpts from company press releases describing the latest hepatitis C developments. Given that these presentations were aimed at investors, information may be slanted so as to highlight its financial implications.

Clinical trial data for promising agents is expected to be presented by researchers at upcoming medical conferences in the field, including the annual meeting of the European Association for the Study of the Liver (EASL 2010) in April, the Digestive Disease Week (DDW 2010) conference in May, and the American Association for the Study of Liver Diseases' Liver Meeting (AASLD 2010) in late October.

Vertex Plans to Seek Approval of Telaprevir in Second Half of 2010

Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex: "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."

The hepatitis C program is part of a larger effort to become "a fully-capable biopharmaceutical company," and Vertex is currently working on or planning clinical trials for therapies for cystic fibrosis, rheumatoid arthritis, and epilepsy.

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-naive 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-naive 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-naive and treatment-failure patients.

Potential Future Combination Regimens for HCV with Telaprevir and the HCV Polymerase Inhibitor VX-222

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.

The full press release is available online.

For more information about Vertex.

InterMune Provides 2010 Milestones for RG7227 (ITMN-191)

Dan Welch, Chairman, Chief Executive Officer and President of InterMune: "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 100 mg RG7227 twice-daily or 200 mg 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."

(RG7227): Clinical Development Highlights and Recent Events

Enrollment began in August 2009 of the company's Phase 2b study of RG7227 in combination with Pegasys) (pegylated interferon alfa-2a) and Copegus (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 100 mg twice-daily ritonavir: 100mg twice-daily RG7227; 200mg once-daily RG7227; 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.

The full press release is available online.

For more information about InterMune, visit http://www.intermune.com.

Idenix Pharmaceuticals Highlights Progress in Three HCV Programs

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):
Cohort
Median Change
in HCV RNA
(log10) at Day 14
Patients with
Undetectable Viral
Load at Day 14
(<15 IU/mL)
50 mg/day IDX184 +
PegIFN/Ribavirin (n=8)
-3.66
2
Placebo + PegIFN/Ribavirin (n=2)
-1.70
0

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."

The full press release is available online.

For more information about Idenix, see www.idenix.com.

1/22/10

Sources

Vertex. Vertex Reviews 2010 Business Priorities to Support Goal of Becoming Fully-Capable Biopharmaceutical Company. Press release. January 10, 2010.

InterMune. InterMune Provides Program Update and 2010 Milestones for RG7227 (ITMN-191). Press release. January 11, 2010.

Idenix. Idenix Pharmaceuticals Highlights Progress in Three HCV Programs. Press release. January 11, 2010.


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


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