October 25, 2010

Early use of TIPS in patients with cirrhosis and variceal bleeding

N Engl J Med. 2010 Jun 24;362(25):2370-9.

García-Pagán JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A, Abraldes JG, Nevens F, Vinel JP, Mössner J, Bosch J; Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group.

Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, University of Barcelona, Barcelona, Spain. jcgarcia@clinic.ub.es

Comment in:

N Engl J Med. 2010 Sep 30;363(14):1375; author reply 1376.
N Engl J Med. 2010 Sep 30;363(14):1375; author reply 1376.
N Engl J Med. 2010 Sep 30;363(14):1375-6; author reply 1376.
N Engl J Med. 2010 Jun 24;362(25):2421-2.
Ann Intern Med. 2010 Oct 19;153(8):JC4-6.

Abstract

BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients.

METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients).

RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events.

CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)

2010 Massachusetts Medical Society

PMID: 20573925 [PubMed - indexed for MEDLINE]

Source
Gastroenterology. 2010 Aug 16. [Epub ahead of print]

Sulkowski MS, Shiffman ML, Afdhal NH, Reddy KR, McCone J, Lee WM, Herrine SK, Harrison SA, Poordad FF, Koury K, Deng W, Noviello S, Pedicone LD, Brass CA, Albrecht JK, McHutchison JG; IDEAL study team.

Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment is frequently complicated by anemia from ribavirin (RBV)-related hemolysis and peginterferon-alfa (PEG-IFN)-related bone marrow suppression. We investigated the relationships among treatment outcomes, anemia, and its management with RBV dose reduction and/or erythropoiesis-stimulating agents (ESAs).

METHODS: We analyzed data from a trial conducted at 118 United States academic and community centers in treatment-naïve patients with HCV genotype 1. Patients were treated for as many as 48 weeks with 1 of 3 PEG-IFN/RBV regimens. ESAs were given to anemic patients (hemoglobin [Hb] <10 g/dL) after RBV dose reduction. Sustained virologic responses (SVR) were assessed based on decreases in Hb, anemia, and ESA use.

RESULTS: While patients received treatment, 3023 had their Hb levels measured at least once. A SVR was associated with the magnitude of Hb decrease: >3 g/dL, 43.7%; ≤3 g/dL, 29.9% (P < .001). Anemia occurred in 865 patients (28.6%); 449 of these (51.9%) used ESAs. In patients with early-onset anemia (≤ 8 weeks of treatment), ESAs were associated with higher SVR rate (45.0% > 25.9%; P < .001) and reduced discontinuation of treatment because of adverse events (12.6% < 30.1%, P < .001). ESAs did not affect SVR or discontinuation rates among patients with late-stage anemia.

CONCLUSIONS: Among HCV genotype 1-infected patients treated with PEG-IFN/RBV, anemia was associated with higher rates of SVR. The effect of ESAs varied by time to anemia; patients with early-onset anemia had higher rates of SVR with ESA use, whereas no effect was observed in those with late-onset anemia. Prospective trials are needed to assess the role of ESAs in HCV treatment.

Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 20723545 [PubMed - as supplied by publisher]

Source

Vertex Quarter Blemished by Hep C Hiccup

By Adam Feuerstein 10/25/10 - 07:44 PM EDT

CAMBRIDGE, Mass. (TheStreet) -- Two words investors don't want to see in a Vertex Pharmaceuticals'(VRTX_) press release: Viral breakthrough.

Yet that's what Vertex disclosed Monday in its otherwise unremarkable third-quarter earnings report. A phase IIb study combining two of the company's experimental hepatitis C drugs -- VX-222 and telaprevir -- had to be modified after viral loads in some patients rebounded during the first four weeks of treatment.

The adversely affected patients were being treated with a low-dose of VX-222 plus telaprevir. That dosing regimen is being discontinued due to the viral breakthrough, Vertex said. Other hepatitis C patients continue treatment in the ongoing study with a high dose of VX-222 plus telaprevir as well as four-drug regimens of VX-222, telaprevir, long-acting interferon and ribavirin.

The future of hepatitis C treatment is in the combination of new drugs that act powerfully and directly against the virus, eliminating the need for patients to rely on older, established drugs like long-acting interferons and ribavirin which work in less than half of patients and causes bothersome side effects.

Vertex's effort in this race is centered around the VX-222/telaprevir combination, so Monday's disclosure of a hiccup in the ongoing phase II study is likely to raise some investor concerns. Other companies developing their own direct-acting antiviral combinations include Roche, Bristol-Myers Squibb(BMY_), Gilead Sciences(GILD_)and Boehringer Ingelheim.

In its defense, Vertex said on a conference call that viral breakthrough in the low-dose VX-222/telaprevir arm of the study was not accompanied by any safety issues. Patients continue to be treated with a high-dose VX-222-telaprevir combination, also without safety issues. None of the patients in the remaining three arms of the 100-patient study have experienced viral breakthrough, the company said.

Vertex is gearing up to complete an approval filing for telaprevir in the coming weeks based on data from phase III studies which demonstrated the drug's ability to sharply increase the hepatitis C cure rate compared to the current standard of care. Vertex will seek telaprevir's approval for both hepatitis C patients starting treatment for the first time as well as patients who have failed to respond to previous treatment.

Data from these pivotal studies of telaprevir will be presented at the American Association for the Study of Liver Disease (AASLD) annual meeting, which runs Oct. 29 through Nov. 2. The AASLD meeting will also showcase for the first-ever presentation of phase III data from a Merck's(MRK_) competing hepatitis C drug boceprevir.

Vertex is hoping to launch telaprevir early next year. The drug will be dosed three times a day initially in combination with long-acting interferon and ribavirin, but Monday the company announced plans to start a new phase III trial testing a more convenient, twice-daily dose of telaprevir.

A completed phase II study of twice-daily telaprevir was presented at last year's AASLD meeting and showed promising results.
 
From the financial ledger, Vertex's third quarter loss widened to $209 million, or $1.04 a share from $149.6 million, or 84 cents a share, in the year-ago quarter.
 
Vertex ended the September quarter with $1.2 billion in cash, including $400 million raised last month in a new convertible debt offering. Vertex said it remains on track to lose $750 million this year, in line with previous guidance.

Vertex shares closed Friday at $37.32, ahead of the company's earnings announcement.

--Written by Adam Feuerstein in Boston.

Source
 
Also See:
Vertex Pharmaceuticals Reports Third Quarter 2010 Financial Results and Highlights Progress in Hepatitis C and Cystic Fibrosis Development Programs
Oct. 25, 2010, 4:17 p.m. EDT
- First Phase 3 study to evaluate twice-daily (BID) dosing of a protease inhibitor for hepatitis C -
 
CAMBRIDGE, Mass., Oct 25, 2010 (BUSINESS WIRE) -- --- All patients will receive telaprevir-based combination therapy -

Vertex Pharmaceuticals Incorporated /quotes/comstock/15*!vrtx/quotes/nls/vrtx (VRTX 37.32, +0.89, +2.44%) today announced the initiation of a Phase 3b study called OPTIMIZE that will evaluate twice-daily (BID) dosing of a telaprevir-based combination regimen in people chronically infected with genotype 1 hepatitis C virus (HCV) who have not been treated previously. This is the first Phase 3 study to evaluate twice-daily dosing of a protease inhibitor for the treatment of hepatitis C. OPTIMIZE will not include a control arm of pegylated-interferon and ribavirin alone.

"The sustained viral response rates, or viral cures, seen across a broad range of people in the Phase 3 studies of telaprevir set a high bar in the development of treatments for hepatitis C, and we are committed to studying new ways to further improve treatment," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "High viral cure rates were demonstrated in the Phase 2 study of twice-daily telaprevir and we're looking forward to conducting a larger study to confirm these findings."

The OPTIMIZE study will be conducted by Vertex's collaborator, Tibotec.

OPTIMIZE Study Design

In Vertex's recently completed Phase 3 registration program, patients who received telaprevir in combination with pegylated-interferon and ribavirin took telaprevir three times daily (750mg; every eight hours). OPTIMIZE is a randomized, open-label, Phase 3b study that will evaluate twice-daily dosing (BID) of telaprevir in people chronically infected with genotype 1 HCV who have not been treated previously. The study will be conducted globally at 135 clinical trial sites and enroll approximately 700 people. Patient screening for enrollment in the OPTIMIZE study is expected to start in November 2010.

For the first 12 weeks of the study, all patients will receive 2,250mg of telaprevir taken twice daily (1,125mg; BID) or three times daily (750mg; every eight hours) in combination with pegylated-interferon alpha-2a (PEGASYS(R)) and twice-daily ribavirin. Response guided therapy will be used to determine whether patients receive pegylated-interferon and ribavirin alone for an additional 12 weeks (24 weeks total) or 36 weeks (48 weeks total) based on their treatment response at week 4. The primary endpoint of the OPTIMIZE study is sustained viral response (SVR) 24 weeks after the end of all treatment. The primary objective is to demonstrate non-inferiority of BID telaprevir versus telaprevir dosed every eight hours as measured by SVR.

SVR data from the study are expected as early as 2012. If these data are positive, they may support the submission of a supplemental New Drug Application (sNDA) for twice-daily (BID) dosing of telaprevir.

Phase 2 C208 study

Study C208 was an exploratory, four-arm, randomized, open label, Phase 2 clinical trial that was conducted by Tibotec in Europe in 161 treatment-naive patients with genotype 1 HCV infection. The objective of Study C208 was to explore the safety, efficacy, tolerability and pharmacokinetics of telaprevir administered every 12 hours (1,125mg) or every eight hours (750mg). Each dosing regimen of telaprevir was studied in combination with either PEGASYS(R) or PEGINTRON(R) and ribavirin, the currently approved therapies for chronic HCV infection.

Across the four arms, SVR rates were 82% and 83% in patients treated with telaprevir-based regimens every 12 hours (PEGINTRON and PEGASYS, respectively) and 81% and 85% in patients treated with the every 8-hour regimen (PEGINTRON and PEGASYS, respectively). The primary endpoint was SVR, and data from this study were presented at the 2009 annual meeting of the American Association for the Study of Liver Diseases (AASLD). The Phase 2 C208 data supported the initiation of the Phase 3b OPTIMIZE study.

In the C208 study, the frequency and severity of adverse events (AEs) and the rate of treatment discontinuations were similar to those reported in prior telaprevir trials. The rates of viral breakthrough were similar to the every 8- and every 12-hour regimens. The most common adverse events reported in patients in Study C208 were pruritis, nausea, rash, anemia, flu-like illness, fatigue and headache, and were similar overall between the patient groups receiving every 8-hour dosing and those receiving every 12-hour dosing.

Updates on the status of clinical trials of telaprevir are available online at http://www.clinicaltrials.gov/.

About the Telaprevir Development Program

To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously (ADVANCE and ILLUMINATE) as well as people who had been treated before but did not achieve a viral cure (REALIZE). A fact sheet on the Phase 3 Telaprevir Development Program is available at http://www.vrtx.com/aasld2010.html.

Phase 3 ADVANCE Trial

The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naive patients. The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. As part of a response-guided design, people in the telaprevir-based treatment arms who had undetectable HCV RNA (<25IU/mL, and undetectable by Roche COBAS Taqman HCV test) at weeks 4 and 12 of treatment were eligible to receive a total of 24 weeks of therapy. Patients who did not meet the response-guided criterion but were undetectable at week 24, received 48 weeks of total therapy.

Phase 3 ILLUMINATE Trial

The ILLUMINATE trial was a supplemental, open-label, Phase 3 study designed to evaluate whether there was any benefit in extending therapy from 24 to 48 weeks in people whose hepatitis C was undetectable (<25IU/mL undetectable) at weeks 4 and 12 of therapy. The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups, and evaluated by a non-inferiority analysis.

Phase 3 REALIZE Trial

REALIZE was the second Phase 3 pivotal trial designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon based therapy but did not achieve a cure. REALIZE was the only Phase 3 clinical trial to date of an investigational direct-acting antiviral (DAA) to include all major subgroups of difficult-to-treat patients including null responders, defined as people who had a less than 2 log10 reduction in viral load by week 12 of a prior course of therapy.

Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

About Hepatitis C

Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease.(2) According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.(3)Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, (4,5,6)or viral cure.(1)

Hepatitis C is spread through direct contact with the blood of infected people.(2) Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(2) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(2) If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(7,8,9,10,11) In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.(8) The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.(11) By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(11)

Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.

Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.


PEGASYS(R) and COPEGASYS(R) are registered trademarks of Hoffman-La Roche.

References:

(1)Ghany, m.G., Strader, d.B., Thomas, d.L., Seeff, Leondard B. Diagnosis, Management and Treatment of Hepatitis C; An Update. 2009. Hepatology. 2009;49 (4):1-40. (2) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010. (3) Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Available at http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Accessed May 25, 2010. (4)Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965. (5) Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982. (6)McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593. (7) Morgan T.R, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115). (8)Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138: 513-521 (9) Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755. (10) Veldt, B.J., Heathcote, J., Wedmeyer, H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684. (11) Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.

Safe Harbor Statement

This press release contains forward-looking statements, including statements regarding (i) the viral cure rates in Phase 3 studies of telaprevir setting a high bar in the development of treatments for HCV and the Company's commitment to studying new ways to further improve treatment; (ii) the possibility that a larger study will confirm the findings from the Phase 2 study of twice-daily telaprevir; (iii) the design of the trial, including the objective of the trial and the primary endpoint, the expectation that patient screening will start in November 2010, the number of patients the Company expects to enroll, and the number and location of clinical trial sites, and that the trial will be conducted by Tibotec; (iv) the expectation that SVR data from the trial will be available as early as 2012 and (v) the expectation that if the data are positive they may support the submission of a supplemental New Drug Application for twice-daily dosing of telaprevir. While the company believes the forward-looking statements contained in this press release are accurate, those statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. These risks and uncertainties include, among other things, the risk that efforts to develop telaprevir may not proceed due to technical, scientific, commercial, financial or other reasons, that clinical trials may not proceed as planned due to drug supply or patient enrollment issues, that additional clinical trials of telaprevir dosed twice-daily may not reflect the results obtained to date, that an adverse event profile for telaprevir could be revealed in further nonclinical or clinical studies that could put further development of telaprevir in jeopardy or adversely impact their therapeutic value and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

SOURCE: Vertex Pharmaceuticals Incorporated

Vertex Pharmaceuticals Incorporated

Media:
Amy Pasqua, 617-444-6992
or
Dawn Kalmar, 617-444-6992
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Zachry Barber, 617-444-6992

or

Investors:
Michael Partridge, 617-444-6108
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Lora Pike, 617-444-6755
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Matthew Osborne, 617-444-6057

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October 25, 2010 04:17 PM Eastern Daylight Time

- Hepatitis C: New Drug Application submission for telaprevir on track for fourth quarter 2010-

- Cystic Fibrosis: Phase 3 registration program ongoing for VX-770-

- Pipeline: Ongoing proof-of-concept clinical trials in hepatitis C, cystic fibrosis, epilepsy and rheumatoid arthritis-

- Financial: Company ends third quarter with a cash position of $1.2 billion-

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today reviewed recent business and clinical progress and reported consolidated financial results for the quarter ended September 30, 2010.

“With the recent completion of our Phase 3 registration program for telaprevir, we remain on track to submit our New Drug Application in the coming weeks, marking what we believe will be an important milestone in our effort to bring telaprevir to people with hepatitis C,” said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex Pharmaceuticals.

Mr. Emmens continued, “Later this week, clinical investigators will present Phase 3 data for telaprevir at the annual AASLD meeting in Boston. We continue to have high confidence in the potential for telaprevir to help the majority of people with hepatitis C – regardless of their treatment history – and we look forward to sharing additional telaprevir data with the medical community.

“Importantly, with a cash position of $1.2 billion at the end of the third quarter, we will enter 2011 with the financial strength needed to support the planned launch of telaprevir as well as the continued discovery and development of other new breakthrough medicines,” concluded Mr. Emmens.

Hepatitis C

Telaprevir Phase 3 Program Complete; Rolling NDA Submission On Track

• In the third quarter, Vertex completed its Phase 3 registration program for telaprevir. The company remains on track to complete the submission of its rolling New Drug Application (NDA) for telaprevir in combination with pegylated-interferon and ribavirin in the fourth quarter of 2010 with clinical data from its three Phase 3 trials in people who had not been previously treated for hepatitis C and in people who received prior treatment but were not cured.

Phase 3 ADVANCE and ILLUMINATE Trials to be Presented at AASLD This Week

• Vertex expects that final sustained viral response (SVR or viral cure) and safety data from the Phase 3 ADVANCE and ILLUMINATE trials will be presented as part of oral presentation sessions at the upcoming annual meeting for the American Association for the Study of Liver Diseases (AASLD or The Liver Meeting), being held October 29 to November 2 in Boston. In total, eight Vertex abstracts were accepted for presentation at the AASLD meeting.

Initiation of Phase 3b Clinical Trial to Evaluate Twice-Daily (BID) Dosing of Telaprevir

• Vertex today announced the initiation of a Phase 3b clinical trial to evaluate twice-daily dosing of telaprevir (1,125 mg; BID) compared to three-times-daily dosing of telaprevir (750 mg; q8h) in combination with pegylated-interferon and ribavirin for people with genotype 1 hepatitis C. Patient screening for enrollment in the study is expected to start in November 2010. Additional details on this trial were provided today in a separate press release.

Ongoing Phase 2 Trial Evaluating Combination Regimens of VX-222 and Telaprevir

• Vertex announced today that it has modified its clinical trial evaluating telaprevir dosed in combination with Vertex's lead HCV polymerase inhibitor, VX-222. The company will discontinue Arm A of this study as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing. Arm A was designed to evaluate a two-drug regimen of VX-222 (low dose; 100 mg) and telaprevir (1,125 mg) both dosed twice daily without pegylated-interferon and ribavirin. The additional three arms of the study are continuing without modification, and no viral breakthrough has been reported in these arms.

• This Phase 2 proof-of-concept trial began dosing patients in August 2010 and is designed to evaluate safety and SVR rates using 12-week response-guided regimens of telaprevir/VX-222-based combination therapy in people with genotype 1 hepatitis C. The trial is continuing to evaluate treatment regimens that include four-drug regimens of telaprevir, VX-222, pegylated-interferon and ribavirin, as well as a two-drug regimen of only telaprevir (1,125 mg) and a higher dose of VX-222 (400 mg), both dosed twice daily.

• Trial sites have now completed patient recruitment, which Vertex expects will enable it to reach the initial target enrollment of 100 patients for the study. Vertex expects to obtain on-treatment clinical data from this trial in the first half of 2011 and SVR data in the second half of 2011.

Enrollment Complete in Phase 2 Trial Evaluating Telaprevir in People Co-Infected with Hepatitis C Virus and Human Immunodeficiency Virus

• Vertex today announced that it has completed enrollment of 60 patients in a Phase 2 clinical trial of telaprevir-based regimens in people who are infected with genotype 1 hepatitis C virus and the human immunodeficiency virus (HIV), also know as HCV-HIV co-infection. The primary endpoint of the trial is to evaluate the safety and tolerability of telaprevir-based therapy in people co-infected with HCV and HIV. A secondary endpoint is to evaluate SVR, or viral cure, rates.

• The trial enrolled 13 people who had not previously received treatment for hepatitis C and who were not currently being treated for HIV infection. The trial also enrolled 47 people who had not previously received treatment for hepatitis C and who were currently being treated for HIV infection with highly active antiretroviral therapy (HAART). Of the 47 patients on HAART, 23 were receiving a Reyataz-based regimen and 24 were receiving Atripla.

Cystic Fibrosis

Phase 3 Registration Program for VX-770

• Three trials of the novel cystic fibrosis transmembrane conductance regulator protein (CFTR) potentiator VX-770 are fully enrolled and ongoing as part of a global Phase 3 registration program focused on patients with the G551D mutation.

• Data from the Phase 3 registration program of VX-770 are expected in the first half of 2011. Pending results from the Phase 3 registration program, Vertex expects to submit a New Drug Application for VX-770 in the second half of 2011.

Initiation of Combination Trial of VX-770 and VX-809

• Vertex recently initiated a Phase 2a clinical trial that is evaluating combination regimens of VX-809 and VX-770 in people with cystic fibrosis who have two copies of the F508del mutation. Additional details on this trial can be found in a press release issued on October 18.

Pipeline

Proof-of-Concept Trials of VX-765 in Epilepsy and VX-509 in Rheumatoid Arthritis

• Vertex expects to complete a Phase 2 proof-of-concept trial of the novel caspase-1 inhibitor VX-765 in epilepsy in 2010. Top-line data, including safety and seizure frequency data, are expected later this year.

• Enrollment is ongoing in a Phase 2 proof-of-concept clinical trial of the novel Janus kinase 3 (JAK3) inhibitor VX-509 in rheumatoid arthritis (RA). Interim data from the trial are expected in 2011.

Third Quarter Results

For the quarter ended September 30, 2010, the company’s GAAP net loss was $209.0 million, or $1.04 per share, including certain charges totaling $34.4 million, compared to a GAAP net loss for the quarter ended September 30, 2009 of $149.6 million, or $0.84 per share, including certain charges totaling $22.6 million.

The non-GAAP loss, before certain charges, for the quarter ended September 30, 2010 was $174.6 million, or $0.87 per share, compared to $126.9 million, or $0.71 per share, for the quarter ended September 30, 2009. The increase in the company's 2010 non-GAAP loss was attributable to increased costs to support advancement of telaprevir toward potential launch.

Total revenues for the quarter ended September 30, 2010 were $23.8 million, compared to $25.0 million for the third quarter of 2009.

Research and development (R&D) expenses for the quarter ended September 30, 2010 were $170.4 million, compared to $132.1 million for the third quarter of 2009. The increase reflects greater commercial supply investment for telaprevir and increases in other development activities.

Sales, general and administrative (SG&A) expenses for the quarter ended September 30, 2010 were $48.9 million, compared to $36.6 million for the third quarter of 2009. This increase reflects building of capabilities, including an increase in the number of employees and our commercial investments, to support advancement of telaprevir toward potential launch.

At September 30, 2010, Vertex had $1.2 billion in cash, cash equivalents and marketable securities. In September 2010, Vertex issued $400.0 million of 3.35% convertible senior subordinated notes due 2015, with a conversion price of approximately $48.83 per share.

Full Year 2010 Financial Guidance

This section contains forward-looking guidance about the financial outlook for Vertex Pharmaceuticals.

The company is today reiterating its guidance for 2010 non-GAAP loss of approximately $600 million, as provided on February 4, 2010, and for its 2010 GAAP net loss of approximately $750 million, as provided on July 28, 2010.

Non-GAAP Financial Measures

In this press release, Vertex's financial results are provided both in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, Vertex provides its third quarter 2010 and 2009 loss, and guidance for its projected 2010 loss, excluding stock-based compensation and executive transition expenses, restructuring expense, acquisition-related expenses, loss on exchange of convertible subordinated notes, and revenue and expenses related to certain September 2009 financial transactions. These results are provided as a complement to results provided in accordance with GAAP because management believes these non-GAAP financial measures help indicate underlying trends in the company's business, are important in comparing current results with prior period results and provide additional information regarding its financial position. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, and to manage the company's business and to evaluate its performance. A reconciliation of the other non-GAAP financial results to GAAP financial results is included in the attached financial statements.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company’s strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex’s product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, cancer and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.

Reyataz is a registered trademark of Bristol-Myers Squibb.

Atripla is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) Vertex remaining on track to submit its New Drug Application for telaprevir in the fourth quarter of 2010; (ii) clinical investigators presenting Phase 3 data for telaprevir at AASLD; (iii) the potential for telaprevir to help the majority of people with hepatitis C regardless of their treatment history; (iv) the company entering 2011 with the financial strength needed to support the planned launch of telaprevir as well as the continued discovery and development of other new breakthrough medicines; (v) the expectation that patient screening for the Phase 3b clinical trial of telaprevir will start in November 2010; (vi) the telaprevir/VX-222 Phase 2 clinical trial being designed to evaluate safety and SVR rates using telaprevir/VX-222 based combination therapy and continuing to evaluate treatment regimens that include four-drug regimens and a two-drug regimen of only telaprevir and VX-222; (vii) Vertex expecting to reach its initial target enrollment of 100 patients, and to obtain on-treatment clinical data from the Phase 2 clinical trial of telaprevir and VX-222 in the first half of 2011 and SVR data in the second half of 2011; (viii) the expectation that data from the Phase 3 registration program for VX-770 will be available in the first half of 2011 and the possibility that the company will submit a New Drug Application for VX-770 in the second half of 2011; (ix) the expectation that the company will complete and receive top-line data from a clinical trial of VX-765 in 2010; (x) the expectation that interim data from a Phase 2 clinical trial of VX-509 will be received in 2011; and (xi) the company’s expectations regarding its 2010 non-GAAP and GAAP net loss. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes for each of its planned clinical trials and studies may not be favorable, that regulatory authorities may require supplemental clinical trials in order to support registration of telaprevir and/or VX-770, that planned or potential clinical trials may be delayed or may not be conducted, that the company may not be able to successfully develop telaprevir, VX-770, VX-509, VX-765 or combination therapies involving telaprevir and VX-222 or VX-770 and VX-809, that the company's expectations regarding its 2010 GAAP and non-GAAP net loss may be incorrect, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. The company disclaims any obligation to update the information contained in this press release as new information becomes available.

Source
Clinical Gastroenterology and Hepatology
Volume 8, Issue 11 , Pages 924-933, November 2010

Ira M. Jacobson, Gary L. Davis, Hashem El–Serag, Francesco Negro, Christian Trépo

published online 16 August 2010

Abstract

Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies.

Keywords: Hepatitis C Virus, Burden of Disease, Hepatic Comorbidities, Prevalence

Abbreviations used in this paper: AASLD, American Association for the Study of Liver Diseases, CHC, chronic hepatitis C, ECC, extrahepatic cholangiocarcinoma, HCC, hepatocellular carcinoma, HIV, human immunodeficiency virus, ICC, intrahepatic cholangiocarcinoma, IDU, injection drug use, IOM, Institute of Medicine, MeSH, Medical Subject Headings, NHANES, National Health and Nutrition Examination Survey, SVR, sustained virologic response

This article has an accompanying continuing medical education activity on page e117. Learning Objectives—At the end of this activity, the learner should be able to appreciate the prevalence of HCV virus infection in the United States as well as worldwide, understand the natural history of HCV infection, including the long-term risk of cirrhosis and hepatocellular cancer, and recognize that a sustained viral response represents a virologic cure.

Conflicts of Interest The authors disclose the following: Ira M Jacobson is a consultant for Abbott, Anadys, Boehringer Ingelheim, Bristol-Meyers Sqibb, Genetech, Gilead Sciences, GlobeImmune, Human Genome Sciences, Merck, Novartis, Pfizer, Pharmasset, Tibotec, Zymogenetics, and Vertex Pharmaceuticals (including advisory board for manuscript); an investigator for Abbott, Anadys, Boehringer Ingelheim, Genetech, Gilead Sciences, GlobeImmune, Human Genome Sciences, Idenix, Merck, Novartis, Pfizer, Pharmasset, Tibotec, Vertex Pharmaceuticals, and Zymogenetics; and a speaker for Bristol-Myers Squibb, Genetech, Gilead Sciences, Merck, and Novartis. Gary L. Davis is an investigator and consultant (including advisory board for manuscript) for Vertex Pharmaceuticals and receives research funding from Human Genome Science, Merck, Roche, Schering-Plough, and Vertex Pharmaceuticals. Hashem El-Serag is a consultant for Vertex Pharmaceuticals (including advisory board for manuscript). Francesco Negro is a consultant for Vertex Pharmaceuticals (including advisory board for manuscript) and receives educational grant support from Roche. Christian Trépo is an investigator and consultant for Vertex Pharmaceuticals (including advisory board for manuscript).

Funding This report is based on material identified by the authors during an advisory board meeting conducted by Vertex Pharmaceuticals Incorporated.

PII: S1542-3565(10)00780-9
doi:10.1016/j.cgh.2010.06.032
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Another Roche FDA approval in the COBAS® TaqMan® viral load portfolio

PLEASANTON, Calif., Oct. 25 /PRNewswire/ -- Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food & Drug Administration (FDA) has approved the real-time PCR COBAS® TaqMan® HCV Test, v2.0. Clinical research organizations have depended on COBAS® TaqMan® technology to support hepatitis C pharmaceutical trials and development. This new test will help clinicians to more confidently and effectively monitor their patients, and to improve treatment outcomes.

"This HCV quantitative test is key to measuring the effectiveness of many antivirals that are currently in clinical development for the treatment of hepatitis C," said Teresa Wright, M.D., Chief Medical Officer of Roche Molecular Diagnostics. "Roche is committed to providing complete diagnostic and treatment solutions for this important global disease."

About COBAS® TaqMan® HCV Test, v2.0 For Use With High Pure System

Designed for use with the High Pure System Viral Nucleic Acid Kit, the COBAS® TaqMan® HCV Test, v2.0 is intended to quantify the amount of hepatitis C viral RNA in human plasma or serum of HCV infected individuals. The test incorporates a manual specimen preparation and the COBAS® TaqMan® 48 Analyzer for automated amplification and detection. Roche now offers HCV viral load test for both automated and manual specimen preparation methods; further demonstrating Roche's commitment in providing workflow options and flexibilities for the diverse needs of laboratories. The test system benefits from the proven contamination controls designed into all COBAS® TaqMan® assays, including built-in Roche-proprietary AmpErase enzyme.

About Hepatitis C

According to the Centers for Disease Control, Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States; approximately 3.2 million persons are chronically infected.

Each year in the U.S. approximately 8,000 – 10,000 people die from hepatitis C-related liver disease. An estimated 3.2 million persons in the United States have chronic hepatitis C virus infection. Most people do not know they are infected because they don't look or feel sick. However, approximately 75 – 85% of people who become infected with hepatitis C virus develop infection.(1)

Hepatitis C infections can range in severity from a mile of "acute" illness lasting a few weeks to a serious, lifelong or "chronic" illness. For most people, acute infection leads to chronic infection. Chronic hepatitis C infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or even death. Hepatitis C is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation in the United States.

Hepatitis C virus is passed when infected blood enters the body of someone who is not infected. People can be infected by sharing contaminated needles, high risk sex with an infected partner, and from an infected mother to her infant during pregnancy and childbirth.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80,000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: http://www.roche.com/.

(1) U.S. Centers for Disease Control. http://www.cdc.gov/

All trademarks used or mentioned in this release are legally protected by law.

For further information please contact:
Jacqueline Wallach
Molecular Diagnostics Communication
925.730.8114

SOURCE Roche
RELATED LINKS
http://www.roche.com/

Source

Immunitor Therapy is a Potential Breakthrough Against Tuberculosis

Oct. 25, 2010, 7:29 a.m. EDT

VANCOUVER, Canada, Oct 25, 2010 (GlobeNewswire via COMTEX) -- Immune Network Ltd. /quotes/comstock/11i!immff (IMMFF 0.00, 0.00, 0.00%) advises that a clinical trial of V5 Immunitor oral vaccine was published earlier this month demonstrating an unexpected powerful effect against tuberculosis, including multi-drug-resistant tuberculosis (MDR-TB) and tuberculosis that is complicated by co-infection with HIV and hepatitis C (HCV). As advised in a September 16, 2010 press release, the Company has entered into a letter of intent to acquire Immunitor oral vaccine technology and products, subject to several conditions including the Company completing its regulatory filings.

V5 Immunitor is an oral vaccine designed and shown to be clinically effective for managing chronic hepatitis B and hepatitis C. The anti-tuberculosis effect has been revealed during a routine clinical trial of V5 in patients with chronic hepatitis C who happened to have tuberculosis. Not only was V5 effective on various liver disease endpoints in 19/20 of the patients, but also, several clinical endpoints associated with TB co-infection improved significantly during the one-month trial leading to discharge of 17 of the 20 patients enrolled. These results were published in the October 2010 edition of Journal of Vaccines and Vaccination, and are available in full text online at http://www.omicsonline.org/2157-7560/2157-7560-1-103.php. An Immunitor press release is available online at http://www.prweb.com/releases/2010/10/prweb4647254.htm.

Immunitor is continuing its clinical work on V5 and other products and updates on progress and further trials will be given accordingly. Immune Network has commenced work toward full regulatory compliance in Canada and USA so that the acquisition of Immunitor may proceed as planned.

Further information is available on the web for Immune Network Ltd. (http://www.immune-network.com/) and for Immunitor (http://www.immunitor.com/).

The Immune Network Ltd logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=8008

Safe Harbor Statement

The information in this release, other than historical information, may be considered forward-looking statements within the provisions of the Private Securities Litigation Reform Act of 1995. Projection and other forward-looking statements and management expectations regarding future events and/or financial performance of the Company -- although given in good faith -- are inherently uncertain and actual events and/or results may differ materially.

This news release was distributed by GlobeNewswire, http://www.globenewswire.com/

SOURCE: Immune Network Ltd

CONTACT: Immune Network Ltd.
immff@yahoo.com

Source

CDC Confirms Man Contracted HIV From 2008 Transfusion

Hepatitis C may play a role in ocular adnexal non-Hodgkin lymphoma

Posted on the OSN SuperSite October 25, 2010

Arch Ophthalmol. 2010;128(10):1295-1299.

The prevalence of hepatitis C infection may be relevant to ocular adnexal non-Hodgkin lymphoma, and hepatitis C may influence the initial appearance of the disease, a study said.

In the retrospective comparative study, medical records of 129 patients with ocular adnexal non-Hodgkin lymphoma were reviewed.

The prevalence of hepatitis C virus (HCV) infection among the patients was 17.8%, and seropositivity for infection was significantly associated with extraorbital lymphoma at the onset, the study said.

A high prevalence of mucosa-associated lymphoid tissue disease (79.8%) was also noted.

Ninety-nine patients who underwent radiotherapy and chemotherapy achieved complete remission, while 23.6% of patients with HCV-seronegative status and 21.7% of patients with HCV-seropositive status relapsed.

"However, the overall and disease-free survival of the infected patients are not statistically different than that of patients who are not infected," the authors said.

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