Idenix Pharmaceuticals and Novartis Pharmaceuticals' Tyzeka

The FDA has approved Tyzeka (telbivudine)for the treatment of chronichepatitis B in adults. Tyzeka will beavailable as a once-a-day regimen tobe taken orally without regard to foodor meals.¹ Tyzeka is marketed by IdenixPharmaceuticals Inc and NovartisPharmaceuticals.²

Liver cancer is the fifth most frequentcancer worldwide, and ~80% ofprimary liver cancer is associated withhepatitis B virus (HBV). Approximately1.25 million Americans currently haveHBV.³ An estimated 70,000 moreAmericans will become infected eachyear, and 5000 will die from HBV complications.⁴ Worldwide, about 350 millionpeople are infected with HBV.³

Patients infected with HBV may havenonspecific symptoms, such as jaundice,fatigue, abdominal pain, loss ofappetite, nausea, vomiting, and jointpain. Sometimes HBV presents withoutany symptoms at all. Because the physicalmanifestations of the disease maybe vague, patients may be unawarethat they are infected with HBV, puttingthemselves at risk for disease progressionand complications and putting othersat risk for catching the disease.³HBV is transmitted through blood.⁴

HBV can be prevented with immunization.Although HBV cannot be cured,new treatment regimens aim toimprove response rates, provide long-termefficacy, reduce drug resistance,improve safety and tolerability, andprovide a convenient route of administration.³

Clinical Trials

Tyzeka was compared with lamivudinein a clinical trial involving 1367patients. Therapeutic response wasevaluated by an end point of viral suppression.Viral suppression was measuredby serum HBV DNA suppressionbelow 100,000 copies/mL, along witheither an improvement in liver diseasemarkers, such as alanine aminotransferasenormalization, or loss of detectablehepatitis B e-antigen (HbeAg).

At the end of 1 year of treatment, 75%of HbeAg-positive patients using Tyzekaachieved therapeutic response, comparedwith 67% of the lamivudine group.

Similar efficacy rates were noted inthe HbeAg-negative group; 75% ofTyzeka patients and 77% of lamivudinepatients responded.¹

Additional results from the studyshowed therapeutic response after 2years. In patients who were initiallyHbeAg-positive, 56% of the Tyzekagroup had undetectable levels, comparedwith 39% of the lamivudinegroup, and 82% of Tyzeka patients whowere initially HbeAg-negative achievedundetectable virus levels and 57% ofthe lamivudine group responded. Itwas noted that the antiviral responseat 24 weeks was associated with betterclinical outcomes after 2 years.⁵

Dosage

Tyzeka will be available as 600-mgonce-daily tablets. Dose adjustmentsare necessary in patients with creatinineclearance (CrCl) less than 50mL/min. Patients with CrCl between 30and 49 mL/min should receive 600 mgevery 48 hours, and patients with CrClless than 30 mL/min should receive600 mg every 72 hours. In patientsreceiving hemodialysis, the 600-mgdose should be administered every 96hours after hemodialysis.²

Safety

Lactic acidosis and severe hepatomegalywith steatosis have been reportedin patients using nucleosideanalogues with or without retroviralagents. As with other HBV therapies,some patients may experience anacute exacerbation of hepatitis B ondiscontinuation of therapy. Close monitoringof liver function is recommendedfor several months after stoppingtreatment with Tyzeka.

Myopathy has been reported weeksto months after initiating therapy withTyzeka. Patients experiencing musclepain or weakness should contact theirprescriber immediately.

Tyzeka is eliminated renally; the doseshould be adjusted appropriately inpatients with CrCl less than 50 mL/min.Tyzeka is not approved for use in pediatricpatients. In clinical trials, 9% ofpatients using Tyzeka had grade 3/4creatine kinase elevations.

Tyzeka is not a cure for HBV, nor willit prevent the transmission of thevirus.¹ The most common side effectsincluded creatine phosphokinase elevation,upper respiratory tract infection,fatigue, headache, abdominalpain, and cough.⁴

Dr. Holmberg is a pharmacist withPhoenix Children's Hospital, Phoenix,Ariz.

References

1. Press Release: TYZEKA (telbivudine) approved in the U.S. as a new treatment for patients with chronic hepatitis B. Available at: www.pharma.us.novartis.com/newsroom/pressReleases/releaseDetail.jsp?PRID=2005. Accessed December 2006.

2. Waknine Y. FDA Approvals: Tyzeka and Humira. Available at: www.medscape.com/viewarticle/548958. Accessed December 2006.

3. Hepatitis B. Available at: www.idenix.com/markets/hbv.html. Accessed December 2006.

4. FDA approves new treatment for chronic hepatitis B in adults. Available at: www.fda.gov/bbs/topics/NEWS/2006/NEW01498.html. Accessed December 2006.

5. Press Release: New telbivudine data from three clinical trials to be presented this week at the American Association for the Study of Liver Diseases (AASLD). Available at: www.pharma.us.novartis.com/newsroom/pressReleases/releaseDetail.jsp?PRID=2006. Accessed December 2006.