Stopping HBV viral replication

Stopping hepatitis B viral replication frequently leads to the achievement of rapid PCR negativity
Achieving PCR negativity in hepatitis B e-antigen (HBeAg)-positive patients
Stopping viral replication frequently leads to polymerase chain reaction (PCR) negativity1,2
The GLOBE trial was an international, phase 3 study of TYZEKA 600 mg vs lamivudine 100 mg for chronic hepatitis B (CHB)3
PCR NEGATIVITY IN HBeAg-POSITIVE PATIENTS(HBV DNA ≤300 COPIES/mL) AT WEEKS 24 AND 52 (n=921)3,4,*,†,‡,§
75% and 67% of patients on TYZEKA and lamivudine, respectively, achieved the primary efficacy end point—therapeutic response—defined as both:
Suppression of HBV DNA to <5 log10
Loss of HBeAg or normal ALT at week 52
60% of patients on TYZEKA achieved PCR negativity at week 52
71/183 patients in the GLOBE trial who achieved undetectable hepatitis B virus (HBV) DNA levels by week 24 went on to e-seroconvert with TYZEKA after 1 year of therapy3,5
*The optimal treatment duration with TYZEKA has not been established.†First-year results of the international GLOBE trial: a phase 3 comparative trial of TYZEKA 600 mg vs lamivudine 100 mg for CHB. Enrolled ITT population included 1367 patients.‡PCR negativity was defined as HBV DNA ≤300 copies/mL.§A subset analysis of the first-year results of the international GLOBE trial. Week 52 efficacy end points and resistance were stratified by week 24 serum HBV DNA.
TYZEKA delivers early, profound HBV DNA suppression by week 8 that continues through week 526
Study 015 was a phase 3 registration trial that included 332 Chinese adult patients, 87% of whom were HBeAg positive6
HBV DNA REDUCTION IN HBeAg-POSITIVE PATIENTS
The primary efficacy end point was reduction in serum HBV DNA (from baseline level) at week 52 of treatment
Secondary efficacy measures included:
Therapeutic response*
Proportions of patients with serum HBV DNA reduction to 5 log10 copies/mL on 2 successive visits
HBV DNA reductions to PCR-undetectable levels
ALT normalization
HBeAg loss and seroconversion (for HBeAg-positive patients)
At week 52, the mean reduction of serum HBV DNA among patients on TYZEKA was –6.3 log10
25% of HBeAg-positive patients on TYZEKA in this study achieved seroconversion after 1 year on therapy
*Among HBeAg-positive patients, therapeutic response was defined as a composite serologic end point with HBV DNA reduced to <5 log10 copies/mL coupled with HBeAg loss or ALT normalization. In HBeAg-negative patients, therapeutic response was defined as HBV DNA reduced to <5 log10 coupled with serum ALT normalization.
Learn how to increase the potential for seroconversion
The importance of PCR negativity in HBeAg-negative patients as demonstrated in the GLOBE study
Guidelines recommend driving HBV DNA to undetectable levels as a primary goal of therapy in HBeAg-negative patients1

75% of patients on TYZEKA* achieved the primary efficacy end point—therapeutic response—defined as both:
Suppression of HBV DNA to <5 log10
Normal ALT at week 52
Rapid 24-week PCR negativity correlates with improved virologic outcomes at week 52 in HBeAg-negative patients
PCR NEGATIVITY (HBV DNA ≤300 COPIES/mL)IN HBeAg-NEGATIVE PATIENTS (n=446)3,†
PCR NEGATIVITY AT WEEK 52BASED ON VIRAL LOADAT WEEK 24 (n=443)3,‡,§
*The optimal treatment duration with TYZEKA has not been established. †First-year results of the international GLOBE trial: a phase 3 comparative trial of TYZEKA 600 mg vs lamivudine 100 mg for CHB. Enrolled ITT population included 1367 patients.‡PCR negativity was defined as HBV DNA ≤300 copies/mL.§A subset analysis of the first-year results of the international GLOBE trial. Week 52 efficacy end points and resistance were stratified by week 24 serum HBV DNA.
171/178 patients who experienced PCR negativity on TYZEKA at week 24 were PCR negative at week 52
Think rapid PCR negativity in your HBeAg-negative patients
80% of patients achieve PCR negativity at 24 weeks and 88% at 52 weeks
96% of patients who achieve PCR negativity at week 24 demonstrate PCR negativity at week 523
Rapid 24-week PCR negativity correlates with improved virologic outcomes at week 52 and minimized resistance
1.1% of patients treated with TYZEKA who achieved PCR negativity at week 24 developed resistance (HBV DNA ≥1000 copies/mL with genotypic mutations) at week 523,§,
§A subset analysis of the first-year results of the international GLOBE trial. Week 52 efficacy end points and resistance were stratified by week 24 serum HBV DNA.As-treated analysis in patients with ≥16 weeks of treatment.
Learn how early, profound HBV DNA suppression can increase the potential for seroconversion
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Seroconversion as a treatment goal

IndicationTYZEKA® is indicated for the treatment of chronic hepatitis B (CHB) 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 in nucleoside treatment-naïve adult patients with HBeAg-positive and HBeAg-negative CHB with compensated liver disease.
Important Safety InformationLactic 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/myositis 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. Isolated cases of rhabdomyolysis have been reported during postmarketing use of TYZEKA. Physicians initiating concomitant treatment with any drug associated with myopathy should monitor patients closely for any signs or symptoms of unexplained muscle pain, tenderness, or weakness. TYZEKA therapy should be interrupted if myopathy is suspected and discontinued if myopathy is confirmed
Peripheral neuropathy has been reported with telbivudine alone or in combination with pegylated interferon alfa-2a and other interferons. Coadministration of TYZEKA with pegylated interferon alfa-2a may increase the risk and severity of peripheral neuropathy. The safety and efficacy of telbivudine in combination with pegylated interferons or other interferons for the treatment of chronic hepatitis B has not been demonstrated. TYZEKA therapy should be interrupted if peripheral neuropathy is suspected and discontinued if peripheral neuropathy is confirmed
Because TYZEKA is eliminated primarily by renal excretion, coadministration of TYZEKA with drugs that affect renal function may alter plasma concentrations of TYZEKA and/or the coadministered drug. Dose adjustment is required in patients with creatinine clearance <50 mL/min, including those with end stage renal disease (ESRD) on hemodialysis. TYZEKA should be administered after hemodialysis
Safety and effectiveness of TYZEKA in pediatric patients under the age of 16 years have not been established
Most common adverse events (≥5%) in the GLOBE and NV-02B-015 trials, regardless of attributability to TYZEKA, were fatigue (13%), increased creatine kinase (CK) [11%], headache (10%), cough (6%), diarrhea (6%), upper abdominal pain (6%), nausea (5%), and pharyngolaryngeal pain (5%)
Peripheral neuropathy was reported as an adverse event in <1% (2/847) of subjects receiving TYZEKA monotherapy. Of TYZEKA-treated subjects <1% (5/847) were diagnosed with myopathy/myositis (presenting with muscular weakness)
Creatine kinase (CK) elevations were more frequent among subjects on TYZEKA treatment. Grade 3 or 4 CK elevations occurred in 13% of patients treated with TYZEKA
To monitor fetal outcomes of pregnant women exposed to TYZEKA, healthcare providers are encouraged to register such patients in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.

References
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol. 2006;4(8):936-962.
Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45(2):507-539.
Data on file. Novartis Pharmaceuticals Corporation.
TYZEKA [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2007.
Lai C-L, Gane E, Liaw Y-F, et al; for the GLOBE Study Group. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007;357:2576-2588.
Hou J, Yin Y-K, Xu D, et al. Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: results at 1 year of a randomized, double-blind trial. Hepatology. 2008;47:447-454.
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