Telbivudine Demonstrates Advantages Over Lamivudine in HBeAg-positive Chronic Hepatitis B
May 17, 2005, 08:53, Reviewed by: Dr.
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"Analysis of the study data across treatment groups suggest that two-year efficacy outcomes, such as persistent control of HBV replication, serum ALT normalization, and HBeAg seroconversion, are associated with achieving rapid viral suppression early in treatment."
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By Idenix Pharmaceuticals, Inc.,
Idenix Pharmaceuticals, Inc. today announced the presentation of interim two-year results from an extended-treatment phase IIb clinical trial for telbivudine demonstrating continuing advantages compared to lamivudine across key efficacy endpoints through two years of treatment in HBeAg-positive chronic hepatitis B patients.
Further analyses of the two-year data indicate that the link between early and profound viral suppression and markers of improved clinical outcomes that were demonstrated at one year extends through two years of treatment. These data were presented today at the 2005 Digestive Disease Week meeting in Chicago, Illinois by Ching-Lung Lai, M.D., lead investigator and Professor of Medicine and Hepatology, Department of Medicine, University of Hong Kong.
The ongoing phase IIb clinical trial compares telbivudine monotherapy and a combination of telbivudine and lamivudine, with lamivudine monotherapy in 104 treatment-naive patients with HBeAg-positive chronic hepatitis B.
Patients receiving telbivudine monotherapy achieved a 1.5 log10, or 30-fold, greater mean viral load reduction compared to patients receiving lamivudine monotherapy at two years. At two years, the percent of patients receiving telbivudine monotherapy in whom levels of serum HBV DNA became undetectable by a sensitive PCR-based assay was 71 percent, more than double that of the 32 percent of patients receiving lamivudine monotherapy (p less than 0.05). Serum ALT normalization, a marker of reduced liver inflammation, was significantly greater in patients treated with telbivudine monotherapy (81 percent) compared to lamivudine monotherapy patients (47 percent) through two years (p less than 0.05). In addition, substantially more patients receiving telbivudine monotherapy (38 percent) achieved HBeAg seroconversion compared to patients in the lamivudine monotherapy group (22 percent).
The rate of treatment failure for patients receiving telbivudine monotherapy (4.5 percent) was significantly lower than the rate of treatment failure in the lamivudine monotherapy group (21 percent) (p less than 0.05). The study results also continue to support a favorable overall safety profile for telbivudine with no substantial safety issues being identified through two years of treatment.
"Analysis of the study data across treatment groups suggest that two-year efficacy outcomes, such as persistent control of HBV replication, serum ALT normalization, and HBeAg seroconversion, are associated with achieving rapid viral suppression early in treatment," said Professor Lai. "Forty-one percent of patients with profound viral suppression after 24 weeks of treatment achieved seroconversion at two years, compared to only 15 percent of patients who did not achieve similar rapid viral response. This correlation between early reduction of viral load levels and longer-term efficacy outcomes suggests that maximizing viral load suppression early in the course of treatment is an important therapeutic goal."
Additional scientific analyses utilized combined two-year data from all patients regardless of treatment group and evaluated two-year efficacy outcomes according to serum HBV DNA level at week 24 of treatment. The results indicated that patients who had HBV DNA levels below 1000 copies/mL by week 24 of treatment had a much higher likelihood of achieving HBeAg seroconversion (41 percent vs. 15 percent), serum ALT normalization (85 percent vs. 51 percent) and undetectable levels of HBV DNA (86 percent vs. 23 percent) after two years of treatment compared to patients whose HBV DNA level was greater than 1000 copies/mL at week 24.
These analyses also demonstrate that patients with viral load levels below 1000 copies/mL were less likely to experience treatment failure than patients with HBV DNA levels above 1000 copies/mL (2 percent vs. 17 percent). Nearly 70 percent of patients receiving telbivudine monotherapy achieved rapid and profound suppression of HBV DNA (to levels below 1000 copies/mL) within the first 24 weeks of treatment, compared to 33 percent of lamivudine monotherapy patients.
"These two-year treatment results for telbivudine demonstrate that, across key measures of virologic and clinical outcomes in hepatitis B patients, the efficacy advantages for telbivudine treatment seen after one year were maintained through two years of treatment," said Nathaniel Brown, M.D., Idenix's executive vice president clinical development and chief medical officer. "We are encouraged by these longer-term phase IIb data and look forward to the results of the comprehensive telbivudine phase III GLOBE study, evaluating more than 1370 hepatitis B patients worldwide, which we expect to be available in the fall of this year."
Study Design
The telbivudine phase IIb program is comparing the safety and antiviral effectiveness of telbivudine, and telbivudine in combination with lamivudine, with a control arm of lamivudine monotherapy in two sequential, linked trials. The first clinical trial enrolled 104 treatment naive HBeAg-positive adults with chronic hepatitis B for one year of treatment in one of five daily treatment regimens: telbivudine 400 mg, telbivudine 600 mg, telbivudine 400 mg + lamivudine 100 mg, telbivudine 600 mg + lamivudine 100 mg or standard lamivudine therapy (100 mg per day).
The telbivudine phase IIb extended treatment clinical trial is a two-year extension of the initial one-year phase IIb clinical trial, to obtain comparative data for telbivudine and lamivudine for a total of three years. The two patient groups treated with telbivudine monotherapy in the initial one-year clinical trial are receiving 600 mg/day of telbivudine in the extension trial. The patient groups that received telbivudine combined with lamivudine in the initial one-year clinical trial are receiving telbivudine 600 mg/day combined with lamivudine 100 mg/day in the extension trial. The patients who received lamivudine 100 mg/day in the initial one-year trial continue to receive such treatment in the extension trial. The two-year phase IIb analysis includes combined data from the completed one-year plus one year of the extended treatment trial.
Results from the initial one-year phase IIb clinical trial were presented by Professor Lai at the American Association for the Study of Liver Diseases (AASLD) in October 2003. After one year of treatment, telbivudine monotherapy demonstrated significantly greater viral suppression, viral clearance by PCR assay, and serum ALT normalization, and a proportionally higher HBeAg seroconversion rate, compared to lamivudine monotherapy.
About Telbivudine
Telbivudine is a specific and selective, oral, once-daily nucleoside being developed for the treatment of chronic hepatitis B. To date, preclinical and clinical data demonstrate a favorable safety profile and marked antiviral activity against HBV.
Telbivudine is currently being evaluated in a two-year international phase III clinical trial comparing telbivudine to lamivudine, referred to as the GLOBE study. The phase III clinical trial is fully enrolled with more than 1370 patients, HBeAg+ or HBeAg-, with compensated liver disease. This trial is ongoing at over 100 clinical sites located in 20 countries in Europe, North America and Asia. Idenix, working jointly with Novartis, currently expects to commence the submission of worldwide marketing applications for telbivudine, beginning with a U.S. New Drug Application filing in late 2005.
The development of 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. 
- These data were presented today at the 2005 Digestive Disease Week meeting in Chicago, Illinois by Ching-Lung Lai, M.D., lead investigator and Professor of Medicine and Hepatology, Department of Medicine, University of Hong Kong.
www.idenix.com
Idenix/Novartis Alliance
Idenix is developing its hepatitis B clinical product candidates, telbivudine and valtorcitabine, in collaboration with Novartis Pharma AG under a development and commercialization arrangement established in May 2003. 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 product candidates that Novartis selects to jointly develop and commercialize as part of the collaboration.
About Idenix
Idenix Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery, development and commercialization 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. The company also has drug discovery and development operations in Montpellier, France and drug discovery operations in 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 2004, the Group's businesses achieved sales of USD 28.2 billion and a pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 81,400 people and operate in over 140 countries around the world.
Forward-looking Statements
This press release contains "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. Statements in this press release other than those that are historical in nature are "forward-looking statements." Forward looking statements, which include statements with respect to the potential therapeutic benefits and successful development of the company's product candidates and the company's drug discovery and research, 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 product 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 product candidates and its discoveries. These and other risks are described in greater detail under the caption "Factors That May Affect Future Results" in Item 7 of the company's quarterly report on Form 10-Q for the quarter ended March 31, 2005 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.
Contact:
Idenix Pharmaceuticals, Inc.
Media: Teri Dahlman (617) 995-9905
Investors: Amy Sullivan (617) 995-9838
CONTACT: Teri Dahlman, Media, +1-617-995-9905, or Amy Sullivan,Investors, +1-617-995-9838, both of Idenix Pharmaceuticals, Inc.
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