Biotech Values

[DewDiligence]

NVS Reports 2-Year Tyzeka vs Lamivudine Data

[The data that formed the basis of the FDA’s approval of Tyzeka were the one-year data from the GLOBE trial of Tyzeka vs Lamivudine. Tyzeka hit its primary endpoint in that trial—a composite definition of response rate—but the clinical benefit of Tyzeka relative to Lamivudine was present in only the e-positive subgroup. At two years, however, Tyzeka blew away Lamivudine on response rate in both the e-positive and e-negative subgroups. Perhaps more important, Tyzeka blew away Lamivudine in both subgroups on the % of patients who were virus-free at two years. (An almost identical PR to this one was issued by IDIX.)]

http://biz.yahoo.com/prnews/061027/nyf034.html?.v=71

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

Friday October 27, 9:00 am ET

GLOBE Data Demonstrates the Correlation Between Hepatitis B Viral Suppression and Clinical Outcomes

Additional Studies Evaluate the Effect of Switching Chronic Hepatitis B Patients to Telbivudine From Two Widely Prescribed Therapies

BOSTON, Oct. 27 /PRNewswire-FirstCall/ -- Novartis (NYSE: NVS ) 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. [This is the study whose results are depicted in #msg-14364568.] 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® 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."

…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 (NYSE: NVS ) 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.
<<