SEBIVO® Demonstrated Better Antiviral Activity Compared to Adefovir in Patients With Chronic Hepatitis B

BARCELONA, Spain -- In a comparative study, SEBIVO® (telbivudine) provided more rapid and profound viral suppression than adefovir both in newly diagnosed HBeAg-positive patients and in those who switched from adefovir to SEBIVO.¹ Additionally, regardless of treatment, a substantial early reduction in virus level correlated with better outcomes such as maintained undetectable levels of virus (PCR-negativity), HbeAg seroconversion and ALT normalization, at one year.² A significantly greater percentage of SEBIVO patients achieved PCR- negativity (38 percent; n=17/45) compared to adefovir-treated patients (12 percent; n=11/90) by six months. These findings were presented at the Annual Meeting of the European Association for the Study of the Liver (EASL).

"These new data demonstrated that SEBIVO provided therapeutic benefit not only for previously untreated patients but also for treated patients who had not achieved sufficient viral suppression," said professor Patrick Marcellin, MD, Head of the Viral Hepatitis Research Unit, Hopital Beaujon, University of Paris and presenter of the study. "Suppressing the hepatitis B virus as fast and effectively as possible is emerging as an important measure of HBV treatment response. It is associated with better treatment outcomes at one year, and SEBIVO achieved this goal better than adefovir."

These new findings come from a trial comparing the efficacy of SEBIVO and adefovir in 135 HBeAg-positive patients with CHB over one year. After six months of treatment, more than twice the number of SEBIVO patients reached target levels of hepatitis B virus (HBV), defined as <3 log(10) copies/mL (49 percent with SEBIVO vs. 22 percent with adefovir). Among the 78 percent of patients in the adefovir group with suboptimal response after six months, those who switched to SEBIVO achieved a two times greater log reduction at one year compared to those who had remained on adefovir treatment (2.1 log(10) versus 0.8 log(10), respectively).

At one year, patients had the option of continuing on or switching to SEBIVO treatment in an ongoing follow-on study. Preliminary data on these patients demonstrated that patients who had a suboptimal response to adefovir (HBV DNA >3 log(10) copies/mL) at one year and then switched to SEBIVO also achieved additional viral suppression (1.95 log(10)) between one and one and a half years. Moreover, 74 percent of patients continually taking SEBIVO through one and a half years achieved PCR-negativity.¹

Both treatments were well tolerated with no drug-attributed serious adverse events. Adverse events for both agents were similar and primarily those associated with viral respiratory infections and gastrointestinal complaints. Two patients experienced grade 3 or 4 neutropenia -- one SEBIVO recipient and one patient in the switch group; both events resolved at follow-up six days later, with continued treatment.

"We are excited by the continued success of SEBIVO in clinical trials, as it further demonstrates SEBIVO's potential to fill an unmet need in chronic hepatitis B treatment and provide rapid, profound and sustained viral suppression," said Douglas Mayers, MD, Idenix's executive vice president and chief medical officer. "We are committed to providing patients with new treatment options for serious viral diseases and eagerly anticipate a decision about the approval of SEBIVO by the European Commission in the next few months."

On February 23, 2007, SEBIVO was recommended for approval by the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP), which reviews drug applications for all 27 countries in the European Union as well as Iceland and Norway. The European Commission is expected to issue a final decision within two to three months. SEBIVO is already approved in 15 countries, including China, Switzerland and the United States. It is marketed as TYZEKA® in the U.S.

Chronic hepatitis B is becoming a major public health issue in Europe. An estimated one million people are infected with HBV every year in Europe, of whom 90,000 will become chronic carriers. Annually, 24,000 will die from cirrhosis or liver cancer.³ The incidence of hepatitis B ranges from 29 cases for every 100,000 people in Western Europe to 523 per 100,000 in Eastern Europe.(3) HBV is 50 to 100 times more infectious than human immunodeficiency virus (HIV).⁴

Telbivudine Presentations at EASL
Additional studies pertaining to telbivudine were presented at EASL. Key presentations included:

-- Professor Thierry Poynard, Hopital Pitie-Salpetriere, University of Paris VI, France, presented findings from a study that examined the post-treatment response in HBeAg-positive patients from the GLOBE study who were treated with telbivudine and lamivudine. After one year, HBeAg-positive patients were eligible to discontinue treatment for efficacy provided they had exhibited HBeAg loss and maintained HBV DNA <5 log(10) copies/mL for at least six months; 39 out of the 134 eligible patients discontinued telbivudine treatment for efficacy. A preliminary analysis of these patients showed that 80 percent or more of the 39 patients who discontinued telbivudine treatment for efficacy exhibited sustained HBeAg responses, demonstrating durability of response when patients have come off treatment due to successful treatment with telbivudine.⁵
-- Professor Jens Rasenack, Albert Ludwigs University, Freiburg, Germany presented a preliminary analysis of the two-year GLOBE data, which showed that telbivudine provided better treatment outcomes in those patients who are eligible for treatment according to international liver association treatment guidelines such as the Asian Pacific Association for the Study of Liver (APASL) and American Association for the Study of Liver Diseases (AASLD) guidelines. Those guidelines recommend patients with elevated levels of HBV DNA and liver enzyme levels (called ALT) that are two times higher than normal undergo antiviral treatment to reduce viral levels in their bodies. In these patients (n=588), telbivudine provided significantly greater HBeAg seroconversion than lamivudine at two years (36 percent vs. 27 percent, respectively) as well as significantly better antiviral efficacy (61 percent vs. 43 percent achieved undetectable virus levels, respectively) and ALT normalization (72 percent vs. 63 percent, respectively) than lamivudine.⁶
-- Rifaat Safadi, Holy Family Hospital, Nazareth, Israel, presented study findings that show that switching patients with inadequate response to lamivudine (residual HBV DNA >3 log) to telbivudine provided significantly improved viral suppression. Patients switched from lamivudine to telbivudine at six months(n=122) experienced an additional reduction of 1.90 log10 copies/mL compared to 0.90 log(10) copies/mL for patients who continued lamivudine (n=124).⁷
-- Jia JiDong, Beijing Friendship Hospital, Beijing, discussed findings from a study of 332 Chinese hepatitis B patients showing that after two years of therapy, telbivudine achieved more profound, sustained viral suppression than lamivudine (HBV DNA reduction of 5.48 vs. 4.00 mean log(10) copies/mL, respectively). In addition, more patients treated with telbivudine achieved HBeAg seroconversion and HBeAg loss at two years compared to patients taking lamivudine, (29 percent (40/138) vs. 20 percent (28/138) and 40 percent (55/138) vs. 28 percent (39/138), respectively).⁸

In clinical studies telbivudine was generally well tolerated with most adverse experiences classified as mild or moderate in severity. Common (>1/100, <1/10) adverse reactions in telbivudine-treated patients reported by one year in the GLOBE study were dizziness, headache, cough, diarrhea, nausea, abdominal pain, skin rash, fatigue and blood testing showing higher levels of liver enzymes, amylase, lipase or creatine kinase. Uncommon (>1/1,000, <1/100) adverse reactions included joint pain, persistent muscle weakness or muscle pain and malaise.

About Idenix/Novartis collaboration
Idenix and Novartis Pharma AG are co-promoting SEBIVO (telbivudine), for the treatment of hepatitis B, and co-developing valtorcitabine, a second hepatitis B compound, and valopicitabine, a hepatitis C compound, under a development and commercialization arrangement established in May 2003. Under this agreement, Novartis and Idenix will co-promote SEBIVO/TYZEKA, valtorcitabine and valopicitabine in the US, France, Germany, Italy, Spain and the UK. Novartis has the exclusive right to commercialize SEBIVO, valtorcitabine and valopicitabine in the rest of the world.

References
1. Marcellin P et al. 76 week follow-up of HBeAG-positive chronic hepatitis B patients treated with telbivudine, adefovir or switched from adefovir to telbivudine. Study abstract. EASL 2007.
2. Marcellin P et al. In hepatitis B patients treated with either adefovir or telbivudine, maximal early HBV suppression at 24 weeks predicts optimal one-year efficacy. Study abstract. EASL 2007
3. Van Damme P, et al. Hepatitis B prevention in Europe: a preliminary economic evaluation. Vaccine, Vol. 13, Supplement 1, pp. S54-S57, 1995 International Journal of Epidemiology; V.32; 2003; p118
4. World Health Organization. Hepatitis B fact sheet number 204. Available at www.who.int/mediacentre/factsheets/fs204/en/ Accessed 2/5/07
5. Poynard T. et al. Sustained off-treatment HBeAG response in telbivudine and lamivudine treated HBeAG-positive patients from the GLOBE study. Study abstract. EASL 2007.
6. Rasenack J. et al. Efficacy of telbivudine vs lamivudine at 2 years in patients with HBeAG-positive chronic hepatitis B who are eligible for treatment on guidelines. Study abstracts. EASL 2007.
7. Safadi R. et al. A randomized trial of switching to telbivudine versus continued lamivudine in adults with chronic hepatitis B: results of the primary analysis at week 24. Study abstracts. EASL 2007.
8. Jia JD. et al. Two-year results of a phase III comparative trial of telbivudine vs lamivudine in Chinese patients. Study abstract. EASL 2007.

Source: Idenix Pharmaceuticals

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