New Telbivudine Data From Three Clinical Trials to be Presented This Week at the American Association for the Study of Liver Diseases (AASLD)

BOSTON, Oct. 27 /PRNewswire-FirstCall/ -- Novartis today announced new data from three clinical studies of telbivudine for the treatment of chronic hepatitis B (CHB). Data from the second year of the GLOBE study suggest that viral clearance within the first six months of therapy is associated with better outcomes at one and two years of treatment. Additional results from phase III and phase IIIb studies show that CHB patients treated with telbivudine achieved greater viral clearance at 24 weeks of treatment than patients treated with either lamivudine or adefovir. Additionally, CHB patients who switched to telbivudine achieved greater viral suppression than those who continued on lamivudine or adefovir. The study results will all be presented at the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, which began today.

Two-year results from the GLOBE study, the pivotal registration study comparing telbivudine with lamivudine, showed that in HBeAg-negative patients, undetectable virus levels (PCR-negativity) were achieved by 82 percent of telbivudine-treated patients and 57 percent of lamivudine-treated patients. In HBeAg-positive patients, 56 percent of telbivudine-treated patients and 39 percent of lamivudine-treated patients achieved viral clearance.

"In chronic disease that often requires long-term treatment, it is important to know how patients may respond over time," said Adrian M. Di Bisceglie, M.D., Professor of Medicine, Chief of Hepatology, Division of Gastroenterology and Hepatology, St. Louis University and Co-Director, Saint Louis University Liver Center. "As a robust two-year analysis of a hepatitis B treatment the GLOBE results provide further evidence that the 24-week antiviral response is associated with improved clinical outcomes at two years."

The most common adverse events (>5%) in the one-year results of the GLOBE study were upper respiratory tract infection (14%), fatigue and malaise (12%), abdominal pain (12%), nasopharyngitis (11%), headache (11%), blood CPK increased (9%), cough (7%), nausea and vomiting (7%), influenza and influenza-like symptoms (7%), post-procedural pain (7%), diarrhea and loose stools (7%) and pharyngolaryngeal pain (5%).

Approximately 350 million people worldwide are living with CHB a virus that affects the liver and is estimated to be 50 to 100 times more infectious than human immunodeficiency virus (HIV). Hepatitis B virus can cause chronic lifelong infection and today there is no cure.

Key findings from the GLOBE study

The primary efficacy endpoint of the GLOBE study at one year 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). At one year, therapeutic response was 75 percent in HBeAg-positive patients treated with telbivudine and 67 percent in those patients treated with lamivudine, while the response was 75 percent and 77 percent, respectively, for HBeAg-negative patients. At two years, in HBeAg-positive patients, therapeutic response was 64 percent among patients treated with telbivudine and 48 percent for those patients treated with lamivudine, while the response was 78 vs. 66 percent, respectively, for HBeAg-negative patients. Telbivudine achieved mean HBV DNA reduction at two years of -5.7 log10 in HBeAg-positive patients and -5.0 log10 in HBeAg-negative patients. Lamivudine-treated patients achieved mean HBV DNA reductions of -4.4 log10 in HBeAg-positive patients and -4.2 log10 in HBeAg-negative patients.

Achieving PCR negativity early in therapy decreased the incidence of viral resistance. For telbivudine-treated patients who achieved PCR negativity at week 24, the per-protocol rates of resistance at two years were 4 percent in HBeAg-positive patients and 2 percent HBeAg-negative patients. Per GLOBE study protocol, resistance was defined as HBV DNA return to >5 log, or to within 1 log of baseline. At 2 years, in HBeAg-positive patients, 17.8 percent of telbivudine patients and 30.1 percent of lamivudine patients exhibited viral resistance per protocol. In the HBeAg-negative patient group, 7.3 percent of telbivudine patients and 16.6 percent of lamivudine patients exhibited viral resistance per protocol. Analysis of viral resistance defined as rebound of HBV DNA after initial suppression to 1 log increase above nadir was also performed and was found in 21.6 percent of telbivudine patients and 35.0 percent of lamivudine patients in the HBeAg-positive group and in 8.6 percent and 21.9 percent, respectively, in the HBeAg-negative group.

Disease exacerbation (ALT flares) occurred in 2.8 percent of telbivudine patients and 8.4 percent of lamivudine during the study. Using AASLD criteria, ALT flares in this case are defined as ALT>10x ULN and >2.0 x baseline. Grade 3/4 creatine kinase (CK) elevations were experienced in 13 percent of telbivudine patients and 4 percent of lamivudine patients.

Additional Findings From The Switch Studies

A one-year open label head-to-head trial against adefovir was designed to evaluate whether HBeAg-positive CHB patients previously treated with adefovir would benefit from switching to telbivudine compared to continued adefovir treatment. Greater reductions in viral load were seen both in patients who received telbivudine for the 52-week duration of the trial (-6.55 log(10) copies/mL) and in those who were switched to telbivudine after 24 weeks of adefovir treatment (-6.44 log(10) copies/mL) compared with those patients treated with adefovir for the duration of the trial (-5.72 log(10) copies/mL).

The adefovir vs. telbivudine study (018 study) enrolled 135 adults with HBeAg-positive compensated chronic hepatitis B. Patients were initially randomized (2:1) to adefovir 10 mg/d or telbivudine 600 mg/d for 24 weeks, with a secondary randomization (1:1) of adefovir recipients to either continue adefovir or switch to telbivudine at week 24.

In a study of patients previously treated with lamivudine, patients who switched to telbivudine achieved median HBV DNA reductions at 24 weeks of -- 1.66 log(10) copies/mL compared to -0.95 log(10) copies/mL for patients who continued lamivudine treatment. The lamivudine switch study enrolled patients previously treated with lamivudine for 3-12 months. Patients were randomized to either continue lamivudine (100mg/day) or switch to telbivudine (600mg/day) for one year.

About TYZEKA(TM) (telbivudine)

Earlier this week the Food and Drug Administration approved TYZEKA(TM) (telbivudine) as a new treatment for patients with chronic hepatitis B based on one-year results from the GLOBE study. Telbivudine, which will be called TYZEKA in the United States and Sebivo(R) in all other countries, has been approved in the U.S., Switzerland, Brazil, Peru and India. Applications for approval were filed with the European Medicines Agency (EMEA) and the Chinese health authority in the first quarter of 2006.

"We are committed to meeting the needs of patients with hepatitis B and are pleased with the positive study results for telbivudine," said Alex Gorsky, Head of Pharma North American and CEO Novartis Pharmaceuticals Corporation. "TYZEKA was recently approved by the FDA and we are excited to be able to offer physicians and patients with a new treatment option for hepatitis B."

Important Information About TYZEKA Indications and Usage

TYZEKA (TM) (telbivudine) is indicated for the treatment of chronic hepatitis B in adult patients with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

This indication is based on virologic, serologic, biochemical and histologic responses after one year of treatment in nucleoside-treatment-naïve adult patients HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease.

Important Safety Information -- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals. -- Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including TYZEKA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted. -- Cases of myopathy have been reported with TYZEKA use several weeks to months after starting therapy. Myopathy has also been reported with some other drugs in this class. Physicians considering concomitant treatment with these or other agents associated with myopathy should weigh carefully the potential benefits and risks and should monitor and advise patients to report any signs or symptoms of unexplained muscle pain, tenderness or weakness, particularly during periods of upward dosage titration. TYZEKA therapy should be interrupted if myopathy is suspected, and discontinued if myopathy is diagnosed. -- Because TYZEKA is eliminated primarily by renal excretion, co-administration of TYZEKA with drugs that affect renal function may alter plasma concentrations of TYZEKA and/or the co-administered drug. Dose interval adjustment is recommended in patients with creatinine clearance < 50mL/min. -- The safety and efficacy of TYZEKA in liver transplant recipients are unknown. If TYZEKA treatment is determined to be necessary for a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus, renal function should be monitored both before and during treatment with TYZEKA. -- Patients should be advised that treatment with TYZEKA has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination. -- Safety and effectiveness of TYZEKA in pediatric patients under the age of 16 years have not been established. -- Selected treatment-emergent clinical adverse events (Grade 2-4) of moderate to severe intensity reported in the GLOBE study with TYZEKA were: muscle-related symptoms 2%; fatigue/malaise 1%; headache 1%; pyrexia 1%; abdominal pain <1%; arthralgia <1%; cough <1%; diarrhea <1%; gastritis <1%. -- Creatine kinase (CK) elevations were more frequent among subjects on telbivudine treatment. Grade 3/4 CK elevations occurred in 9% of telbivudine-treated patients and 3% of lamivudine-treated patients. -- The optimal treatment duration with TYZEKA has not been established. The relationship of initial treatment response to outcomes such as hepatocellular carcinoma and decompensated cirrhosis is unknown. Idenix/Novartis Collaboration

Idenix is co-promoting its hepatitis B product, TYZEKA, and developing its hepatitis B and hepatitis C clinical product candidates, (valtorcitabine and valopicitabine, respectively), in collaboration with Novartis Pharma AG under a development and commercialization agreement established in May 2003. Under this agreement, Novartis and Idenix will co-promote TYZEKA, and if successfully developed, valtorcitabine and valopicitabine, in the United States, France, Germany, Italy, Spain and the United Kingdom. Novartis has the exclusive right to commercialize licensed approved products in the rest of the world.

About Novartis

Novartis Pharmaceuticals Corporation develops, manufactures, markets and sells leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, gastrointestinal and respiratory areas. 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 is a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. In 2005, the Group's businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 99,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com/.

Forward-looking statements

This release contains certain "forward-looking statements" relating to the Group's business, which can be identified by the use of forward-looking terminology such as "to be presented," "will," "committed," "developing," or similar expressions, or by express or implied discussions regarding the potential approval of TYZEKA in additional markets, the potential development or approval of additional products, or potential future revenues from TYZEKA or other products. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with TYZEKA or other products to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that TYZEKA will be approved for sale in any additional markets, that any other products will be successfully developed, or that TYZEKA or any other products will reach any particular levels of revenue. Management's expectations regarding TYZEKA and any such other products could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; uncertainties relating to clinical trials, including new clinical data and additional analysis of existing clinical data; competition in general; government, industry, and general public pricing pressures; the 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; as well as other risks and factors referred to in the Company's current Form 20-F on file with the U.S. 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.

Contact: Amy Hunter Novartis Infectious Disease and Transplant Immunology +1 862-778-6309 (direct) +1 917-535-2602 (mobile) amy.hunter@novartis.com