Idenix Presents Positive Hepatitis B Results At AASLD And ICAAC Conferences
CAMBRIDGE, Mass., Nov. 1 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. , presented new data for telbivudine and valtorcitabine, drug candidates for the treatment of hepatitis B virus (HBV) infection, that Idenix is developing in collaboration with Novartis Pharma AG. Data presented at the annual meetings of the American Association for the Study of Liver Diseases (AASLD) in Boston and at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C. further support the importance of rapid and profound suppression of hepatitis B virus at the outset of treatment and correlation of such suppression with improved markers of clinical outcome.
Telbivudine Viral Dynamics Studies Demonstrate Rapid and Profound HBV Clearance
A viral dynamics analysis, based on data from the one-year phase IIb clinical trial for telbivudine, was presented at ICAAC by Xiao-Jian Zhou, Ph.D., Idenix's Associate Director, Clinical Pharmacology. This analysis shows that patients treated with telbivudine demonstrated faster and more profound first phase clearance (within the first 2 weeks of therapy) as well as significantly improved second phase clearance (week 3 to week 12 of therapy), compared to lamivudine alone. Viral dynamics modeling indicated that the greater second phase viral clearance achieved with telbivudine was associated with a more rapid clearance of HBV-infected cells from the body, which correlates with improved clinical outcome observed in telbivudine-treated patients at one year. The important measures of clinical outcome observed include higher rates of hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization and suppression of virus to undetectable levels in the blood.
A second viral dynamics presentation, made at AASLD by Avidan Neumann, Ph.D., Associate Professor, Head, Laboratory of Viral Dynamics Modeling, Bar- Ilan University, Israel, evaluated virologic data from the 4-week phase I dose escalation trial of telbivudine. This analysis confirmed the rapid and profound first and second phases of viral clearance observed in telbivudine- treated patients and, unexpectedly, found second phase viral decline slope to be dose-dependent with telbivudine.
"This result, which is not predictable by the current model of hepatitis B viral dynamics, could indicate that the high degree of antiviral effectiveness achieved by telbivudine may be associated with additional mechanisms of action, not previously considered," commented Prof. Neumann.
Telbivudine is currently in phase III clinical development. The ongoing international phase III clinical trial, referred to as the GLOBE study, is designed to evaluate telbivudine head-to-head against lamivudine. The GLOBE study, which has enrolled more than 1350 patients, is the largest hepatitis B registration trial to date, with sites in over 20 countries including China, where hepatitis B is estimated to affect approximately 120 million people. Patient enrollment in the GLOBE study was completed ahead of schedule in April 2004. Idenix expects to file worldwide marketing applications for telbivudine beginning in late 2005.
"Telbivudine's mechanism of action, its marked and rapid antiviral activity demonstrated in clinical trials, and its favorable safety profile supports its anticipated use as first line therapy for patients with chronic hepatitis B," said Dr. Nathaniel Brown, Idenix's executive vice president, clinical research, and chief medical officer. "As we continue to evaluate data from our clinical trials of telbivudine and move closer to an NDA submission, we believe that telbivudine may provide significant efficacy improvements over current therapies, with an excellent safety profile and with convenient once daily oral dosing."
Valtorcitabine Results Support Development In Combination with Telbivudine Valtorcitabine ("val-LdC") is being developed by Idenix, in collaboration with Novartis, as part of a fixed-dose combination therapy with telbivudine for those hepatitis B patients unable to achieve optimal therapeutic response with a single agent. Preclinical data support the development of this combination therapy by demonstrating that the combination of valtorcitabine and telbivudine is synergistic for inhibition of HBV replication.
Prior to the initiation of telbivudine/valtorcitabine clinical evaluation, a phase I randomized, double blind, placebo-controlled dose escalation clinical trial of valtorcitabine alone was undertaken to evaluate its antiviral activity, safety and pharmacokinetics. Data from this clinical trial was presented at AASLD by Dr. Ching-Lung Lai, Professor of Medicine at the University of Hong Kong. The trial comprised seven valtorcitabine dosing cohorts ranging from 50 to 1200 mg/day given orally, once daily for 4 weeks, with a 12-week follow up period. The trial enrolled HBeAg positive adult patients with chronic hepatitis B. At baseline, patients had serum HBV DNA greater than 7 log10 copies/mL and serum ALT levels 1 to 5 times the upper limit of normal. Results indicate that valtorcitabine treatment produced substantial, dose-dependent viral load (serum HBV DNA) reductions. Patients receiving the 900 mg/day dose of valtorcitabine achieved a mean 3.04 log10 reduction in blood serum HBV DNA levels, representing a 99.9% reduction in viral load with only 4 weeks of treatment. Valtorcitabine also demonstrated a favorable safety profile in all patient cohorts. There was no observed pattern of treatment-related clinical side effects or laboratory abnormalities.
The results of the phase I clinical trial support continued development of valtorcitabine as part of a fixed-dose combination with telbivudine. Idenix expects to begin a phase IIb clinical trial for valtorcitabine in combination with telbivudine by year-end 2004.
The development of these drug candidates (telbivudine and the telbivudine/valtorcitabine combination) for the treatment of chronic hepatitis B demonstrates the commitment of Idenix and Novartis Pharma AG to develop and introduce new, improved treatment options in this area of significant unmet medical need.
About Hepatitis B
Despite the presence of global immunization programs for hepatitis B virus, the World Health Organization (WHO) has estimated that approximately 350 million people, or 5% of the world's population, are chronically infected with hepatitis B virus. Chronic hepatitis B can lead to cirrhosis, liver failure and hepatocellular carcinoma (liver cancer). The WHO also estimates that annually over 50 million people become infected with hepatitis B virus and that more than one million individuals die from HBV-related chronic liver disease demonstrating the urgent need for new treatment.
About Idenix
Idenix Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases. Idenix's current focus is on the treatment of infections caused by hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV). Idenix's headquarters are located in Cambridge, Massachusetts and it has drug discovery operations in Montpellier, France and Cagliari, Italy. For further information about Idenix, please refer to http://www.idenix.com/.
About Novartis
Novartis AG is a world leader in pharmaceuticals and consumer health. In 2003, the Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 80,000 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com/.
Idenix/Novartis Strategic Alliance
In May 2003, Idenix and Novartis Pharma AG entered into a broad collaboration covering the development and commercialization of Idenix's pipeline, including the grant to Novartis Pharma AG of a license to Idenix's hepatitis B drug candidates. The collaboration also provides Novartis with an exclusive option to license and participate with Idenix in the development and commercialization of other drug candidates in Idenix's portfolio, including Idenix's hepatitis C compounds. In addition to license fee payments and reimbursement of certain expenses, Novartis will make payments to Idenix contingent on milestones being achieved for Idenix drug candidates that Novartis selects to jointly develop and commercialize as part of the collaboration.
Forward-looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Act of 1995. Statements in this press release other than those that are historical in nature are "forward- looking statements." Such forward looking statements, which include statements with respect to the potential therapeutic benefits and successful development of drug candidates that the company has under development and the company's drug discovery, research and clinical development, regulatory approval processes and commercialization activities, are subject to numerous factors, risks and uncertainties that may cause actual events or results to differ materially from the company's current expectations. These risks and uncertainties relate to the results of clinical trials and other studies with respect to the drug candidates that the company has under development, the timing and success of submission, acceptance and approval of regulatory filings, the company's dependence on its collaboration with Novartis Pharma AG, the company's ability to obtain additional funding required to conduct its research, development and commercialization activities, the ability of the company to attract and retain qualified personnel and the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its drug candidates and its discoveries. These and other risks are described in greater detail in the "Risk Factors" section of the company's quarterly report on Form 10-Q for the quarter ended June 30, 2004 and filed with the Securities and Exchange Commission and other filings that the company makes with the Securities and Exchange Commission.
All forward-looking statements reflect the company's expectations only as of the date of this release and should not be relied upon as reflecting the company's views, expectations or beliefs at any date subsequent to the date of this release. Idenix anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.
Idenix Pharmaceuticals, Inc.CONTACT: Media: Teri Dahlman, +1-617-995-9905 or Investors: AmySullivan, +1-617-995-9838, both of Idenix Pharmaceuticals
Web site: http://www.idenix.com/