Telbivudine Approved in European Union for Hepatitis B Treatment

On April 30, the European Commission approved telbivudine for the treatment of chronic hepatitis B virus (HBV) infection in adults. The approval will allow the drug to be sold in all 27 countries in the European Union.

The Food and Drug Administration (FDA) approved telbivudine for sale in the U.S. in October 2006. While the drug is marketed in the U.S. as Tyzeka, it will be sold under the brand name Sebivo in Europe. The marketing is a collaborative venture between Idenix Pharmaceuticals and Novartis Pharma AG.

Telbuvudine, a nucleoside analog polymerase inhibitor, is taken orally once daily. Unlike some other anti-HBV agents, studies have shown that it is not active against HIV.

Below is an excerpt of an Idenix press release announcing the approval:

Sebivo (Telbivudine) Approved in European Union as a New Treatment for Chronic Hepatitis B Patients

CAMBRIDGE, Mass., April 30 -- PRNewswire-FirstCall -- The European Commission today approved Sebivo (telbivudine), a new once-a-day oral treatment for adult patients with chronic hepatitis B (CHB) and evidence of viral replication and active liver disease.

The European Commission decision applies to all 27 countries in the European Union as well as Iceland and Norway. Launches are expected to start in the second quarter of 2007 beginning with the United Kingdom and Germany. The approval of Sebivo in Europe triggers a milestone payment from Novartis Pharma AG to Idenix. In addition to the European Union, Sebivo is currently approved in more than 15 major markets, including the United States (where it is marketed as Tyzeka (telbivudine)), Canada, Switzerland, and China.

"The approval of Sebivo now offers Europeans infected with chronic hepatitis B a new treatment option," said Professor Thierry Poynard of Hopital Pitie-Salpetriere, University of Paris VI, France and an investigator in the phase III GLOBE study. "There is no cure for chronic hepatitis B. High hepatitis B viral load increases the risk of serious complications. To reduce this risk, the goal of therapy is to suppress the hepatitis B virus as much as possible, and to maintain that decrease over time."

Worldwide regulatory submissions have been based primarily on one-year data from the GLOBE study, the largest worldwide registration trial including hepatitis B e-antigen (HBeAg)-positive and HBeAg-negative patients with CHB. The worldwide phase III GLOBE study compared telbivudine to lamivudine, a commonly used antiviral therapy for the treatment of CHB, in 1,367 patients. In the European Union, participating countries included the Czech Republic, France, Germany, Greece, Italy, Poland, Spain, and the UK.

"The European approval of Sebivo is another significant achievement for Idenix," said Jean-Pierre Sommadossi, chief executive officer and chairman of Idenix. "Working with our alliance partner, Novartis, we have gained approval of Sebivo in more than 40 countries in less than 18 months. The speed with which we have gained these approvals is a testament to our strength and focus on developing new antiviral agents."

Information about Tyzeka/Sebivo (telbivudine)

In the European Union, Sebivo is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease and evidence of viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis.

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

The following information about telbivudine is adapted from the U.S. Food and Drug Administration approved product label. Similar language related to the product's important safety information will pertain to the product in the European Union.

Important Safety Information about Telbivudine

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 telbivudine. 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 telbivudine 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 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. Telbivudine therapy should be interrupted if myopathy is suspected, and discontinued if myopathy is diagnosed.

• Because telbivudine is eliminated primarily by renal excretion, co- administration of telbivudine with drugs that affect renal function may alter plasma concentrations of telbivudine and/or the coadministered drug. Dose interval adjustment is required in patients with creatinine clearance <50mL/min, including those on hemodialysis. Telbivudine should be administered after hemodialysis.

• There are no adequate and well-controlled studies for telbivudine treatment of patients with established lamivudine-resistant or adefovir-resistant hepatitis B virus infection.

• The safety and efficacy of telbivudine in liver transplant recipients are unknown. If telbivudine 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 telbivudine.

• Patients should be advised that treatment with telbivudine has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.

• Safety and effectiveness of telbivudine in pediatric patients under the age of 16 years have not been established.

• Most common adverse events (>/=5%) in the GLOBE trial, regardless of attributability to telbivudine, 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%).

• Creatine kinase (CK) elevations were more frequent among subjects on telbivudine treatment. Grade 3/4 CK elevations occurred in 9% of telbivudine-treated patients.

• The relationship of initial treatment response to outcomes such as hepatocellular carcinoma and decompensated cirrhosis are unknown.

05/04/07

Source
Idenix Pharmaceuticals (via PR Newswire). Sebivo (Telbivudine) Approved in European Union as a New Treatment for Chronic Hepatitis B Patients. Press release. April 30, 2007.