Novartis Pharmaceuticals Corporation Release: GLOBE Study Demonstrates Telbivudine Provides Significantly Greater Response On Antiviral Measures Vs. Lamivudine In Patients With Chronic Hepatitis B, The 10th Leading Cause Of Death Worldwide
EAST HANOVER, N.J., Nov. 14 /PRNewswire-FirstCall/ -- Results from the ongoing GLOBE study demonstrate that the investigational drug telbivudine provides significantly greater response on all evaluated virologic markers compared to lamivudine after one year, in both HBeAg-positive and HBeAg-negative patients with chronic hepatitis B. Idenix Pharmaceuticals, Inc. and Novartis Pharma AG announced the results of the GLOBE study at the 56th Annual Meeting of the American Association for the Study of Liver Diseases in San Francisco today.
Patients treated with telbivudine achieved significantly greater viral suppression than patients treated with lamivudine. Patients treated with telbivudine also experienced significantly higher rates of non-detectable viral levels. The GLOBE study, a phase III clinical trial, includes 1,367 patients from 20 countries and is the largest registration trial of chronic hepatitis B patients ever conducted. The GLOBE study is the first global chronic hepatitis B registration trial to include patients from China, where the disease is highly prevalent.
"Despite recent advances in the treatment of chronic hepatitis B, there remains a need for new safe and effective treatment options," said Dr. Ching-Lung Lai, Professor of Medicine and Chief of the Gastroenterology and Hepatology Division at the University of Hong Kong, and lead investigator of the GLOBE study. "The potent viral suppression achieved with telbivudine has the potential to reduce the serious complications associated with chronic hepatitis B and telbivudine's favorable safety and convenience profile in trials to date also may make it a promising treatment option for patients, including those requiring long-term therapy."
Chronic hepatitis B is the tenth leading cause of death worldwide(1) with approximately 350 million people chronically infected (lifelong infection)(2). Additionally, chronic hepatitis B is responsible for up to 80 percent of the world's primary liver cancer(3), and annually an estimated 1.2 million individuals die from hepatitis B-related chronic liver disease(1).
Key findings from the GLOBE Study
Results from GLOBE indicate that telbivudine produces significantly greater viral suppression compared to lamivudine after one year. Telbivudine patients achieved significantly greater HBV DNA reductions after 52 weeks of treatment in both hepatitis B e antigen (HBeAg) positive patients (-6.5 log(10) vs. -5.5 log(10) with lamivudine; p<0.01) and HBeAg-negative patients (-5.2 log(10), vs. -4.4 log(10) with lamivudine; p<0.01). Similarly, after 52 weeks of treatment, significantly more patients receiving telbivudine achieved clearance of detectable HBV DNA (PCR negative). In HBeAg-positive patients, telbivudine treatment led to loss of detectable HBV DNA in 60 percent of patients compared to 40 percent with lamivudine treatment (p<0.01). In HBeAg-negative patients, telbivudine treatment reduced HBV DNA to below detectable levels in 88 percent of patients, compared to 71 percent with lamivudine treatment (p<0.01).
"We are pleased with the positive one-year GLOBE study results that we will include in key global regulatory submissions currently anticipated to be made by the end of the first quarter 2006 and look forward to obtaining the two-year data from GLOBE to evaluate the longer-term efficacy and safety profile of telbivudine," said James Shannon, Global Head of Development, Novartis Pharma AG.
Analyses of the one-year GLOBE data demonstrate that, regardless of treatment, achieving profound viral suppression early in the course of treatment results in better efficacy outcomes at one year, including non-detectable virus levels (PCR negativity), liver enzyme (ALT) normalization, HBeAg seroconversion and decreased incidence of viral resistance. These results underscore the importance of early and profound suppression in patients with chronic hepatitis B. The majority of telbivudine-treated patients achieved PCR negativity in the first 24 weeks of treatment and 95 percent of those patients remained PCR negative at one year.
The primary efficacy endpoint of the GLOBE study was therapeutic response, a composite endpoint coupling viral suppression (serum HBV DNA suppression below 100,000 copies/mL) with either improved liver disease markers (ALT normalization) or loss of detectable hepatitis B e-antigen (HBeAg). The study successfully reached this endpoint, which was designed to assess if telbivudine was at least as effective as lamivudine, in both HBeAg-positive and HBeAg-negative patients. In HBeAg positive patients, therapeutic response was significantly higher among patients treated with telbivudine (75 percent) compared to patients treated with lamivudine (67 percent) (P<0.05), while the response after one year was similar for HBeAg negative patients taking either treatment (75 percent versus 77 percent, respectively).
Patients receiving telbivudine showed significantly less viral resistance and less treatment failure, compared to patients receiving lamivudine. Telbivudine was associated with fewer and less severe resistance-associated elevations ("flares") of serum ALT levels, a cause of potentially fatal liver failure in chronic hepatitis B patients, compared to lamivudine.
The diverse nature and rate of occurrence of adverse events were similar between telbivudine-treated patients and lamivudine-treated patients. The most common adverse events for telbivudine and lamivudine were upper respiratory infection (14 percent versus 13 percent, respectively), headache (11 percent versus 13 percent, respectively), fatigue (12 percent versus 10 percent, respectively), and nasopharyngitis (11 percent versus 10 percent, respectively). Serum ALT elevations were more common in lamivudine-treated patients compared to telbivudine (8 percent vs. 4 percent, respectively). Transient creatine kinase (CK) elevations, not requiring treatment modification, were more common with telbivudine compared to lamivudine (9 percent versus 3 percent, respectively).
Telbivudine, an investigational drug, is a specific and selective, oral, once-daily nucleoside analog that is being developed for the treatment of chronic hepatitis B and appears to be unique in its preferential inhibition of 2nd strand HBV DNA synthesis.
More About Hepatitis B
Hepatitis B, a virus that infects the liver, is 50-100 times more infectious than HIV(1). The hepatitis B virus can cause lifelong infection, cirrhosis (scarring) of the liver, liver cancer, liver failure, and death(4). Unmet needs in chronic hepatitis B treatment include improved response rates, better long-term efficacy, reduced rates of drug resistance, improved safety and tolerability and more convenient dosing regimens.
GLOBE Study Design
The GLOBE study is a randomized blinded two-year phase III clinical trial comparing telbivudine with the standard therapy lamivudine in 1,367 adults with chronic hepatitis B from 112 clinical centers internationally. Key entry criteria included adults with chronic hepatitis B as evidenced by a positive confirmation of HBeAg (a marker for HBV infection), HBV DNA >6 log 10 copies/mL by COBAS PCR assay, ALT is greater than or equal to 1.3-10 times upper limit of normal (ULN), and compensated liver disease. Patients were stratified for HBeAg status (+ or -) and ALT less than or greater than 2.5 times ULN. The trial was designed to perform primary analysis at Week 52 with later analyses at the completion of the trial of the Week 76 and Week 104 results.
Idenix is developing its hepatitis B clinical product candidates, telbivudine and valtorcitabine, in collaboration with our Swiss affiliate, Novartis Pharma AG under a development and commercialization arrangement established in May 2003. The collaboration arrangement further provides that Novartis Pharma AG and Idenix will co-promote telbivudine and valtorcitabine and other product candidates that Novartis Pharma AG has licensed, if successfully developed and approved for marketing, in the United States, France, Germany, Italy, Spain and the UK. Novartis Pharma AG holds the exclusive license to commercialize telbivudine and valtorcitabine in the rest of the world.
The collaboration also provides Novartis Pharma AG with an exclusive option to license and collaborate with Idenix in the development and commercialization of other product candidates in Idenix's portfolio, including valopicitabine (NM283), a direct antiviral hepatitis C product candidate.
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 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
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG , a world leader in pharmaceuticals and consumer health. In 2004, the Group's businesses achieved net sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.1 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 91,700 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com
The foregoing release contains certain forward-looking statements that can be identified by terminology such as "has the potential to," "promising," "will include," "anticipated," "look forward to," or similar expressions, or by express or implied discussions regarding potential therapeutic benefits and successful development of telbivudine and the anticipated regulatory filings required for the registration of telbivudine, or potential future revenues from telbivudine. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with telbivudine to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that telbivudine will be approved for sale in any market or that it will reach any particular level of revenue. Management expectations regarding telbivudine could be affected by, among other things, uncertainties relating to clinical trials; new clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; Idenix's dependence on its collaboration with Novartis Pharma AG; Idenix's ability to obtain additional funding required to conduct its research, development and commercialization activities; competition in general; government, industry and general public pricing pressures; as well as other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
References 1. Lavanchy D. J Viral Hepat. 2004 Mar 11 (2): 97-107 2. WHO Hepatitis B Fact Sheet #204 3. World Health Organization. Expanded programme on immunization hepatitis B vaccine -- making global progress 4. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/faqb.htmNovartis Pharmaceuticals Corporation
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