Washington Editor

The FDA late Wednesday OK'd the antiviral drug Tyzeka (telbivudine) for chronic hepatitis B, the first U.S. approval for Idenix Pharmaceuticals Inc.

The nucleoside analogue, which is partnered with Novartis AG, has been shown to suppress the hepatitis B virus in adult patients with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Its quick viral suppression improves liver disease outcomes such as fibrosis, cirrhosis, liver cancer and failure, a primary treatment goal.

"This is another option for patients and physicians to treat this really severe viral disease," Chairman and CEO Jean-Pierre Sommadossi told BioWorld Today. "It's a very positive event for them, and that's ultimately what we have to keep in mind."

The worldwide pivotal trial underlying the product's approval, called the GLOBE study, demonstrated Tyzeka's ability to provide rapid viral suppression in the first 24 weeks of treatment. Sommadossi said the Phase III trial, which compared the new agent to lamivudine in 1,367 patients, showed that Tyzeka produced "better clinical outcomes" than the study's comparator agent, the antiretroviral drug Epivir (lamivudine, from GlaxoSmithKline plc).

The primary efficacy endpoint was therapeutic response at one year, a composite that coupled serum hepatitis B virus DNA suppression less than 100,000 copies/mL with either improved liver disease markers (ALT normalization) or loss of detectable hepatitis B e-antigen (HBeAg).

In HBeAg-positive patients, therapeutic response was 75 percent in Tyzeka patients and 67 percent for those on lamivudine, while the one-year response in HBeAg-negative patients was 75 percent for Tyzeka patients and 77 percent in those on lamivudine. Also, patients who achieved nondetectable HBV DNA levels at 24 weeks were more likely to undergo e-antigen seroconversion, achieve undetectable levels of HBV DNA, normalize ALT and minimize resistance at one year.

Cambridge, Mass.-based Idenix filed the new drug application just five years after it entered clinical development. (See BioWorld Today, Jan. 4, 2006.)

The FDA gave Tyzeka a broad, first-line label, Sommadossi said, based on those virologic, serologic, biochemical and histologic responses after one year of treatment in nucleoside treatment-na ve adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease. Nearly 1.25 million people in the U.S. have chronic hepatitis B, which is brought on by the underlying DNA virus. About a third of them require treatment, though Sommadossi indicated that very few of them get it.

"You need to really increase awareness," he said. FDA estimates point to 70,000 new infections per year in the U.S., and some 5,000 of them will die of complications caused by the disease.

Other chronic hepatitis B therapies approved by the agency include interferon, lamivudine, Hepsera (adefovir, from Gilead Sciences Inc.), Viread (tenofovir, also from Gilead) and Baraclude (entecavir, from Bristol-Myers Squibb Co.). Among those different options, Sommadossi noted that Tyzeka offers a more favorable safety profile, including use in women of child-bearing age. In addition, there's a convenience factor, given that it's a once-a-day oral therapy that can be taken with or without food.

Those latter attributes are especially important in Asia, home to about two-thirds of the world's 350 million people affected by hepatitis B. Tyzeka already is under regulatory review in China, with a decision expected sometime next year. That's the same timeline for a regulatory result in the European Union, where the disease is prevalent in southern countries. To be marketed as Sebivo outside the U.S., it's already approved in Switzerland.

The trend for future patient management focuses on combination therapy, Sommadossi said, because "a latent form" of the slowly mutating hepatitis B virus will remain in most patients, necessitating long-term drug treatment. "You need a very rapid and profound viral suppression over a very long period."

Idenix is testing Tyzeka with a second hepatitis B drug in its pipeline, valtorcitabine, with data due next year, and plans to test it with Hepsera around the New Year. Looking ahead, Sommadossi said he expects Tyzeka to be "a major drug at the forefront" of hepatitis B treatment, either as monotherapy or in combination.

"We hope that with increased patient and physician awareness," Sommadossi said, "there would be a larger number of infected individuals that would be treated."

He declined to forecast Tyzeka's sales potential, but noted that its price would be publicized next week. Further headlines could be generated during this weekend's meeting of the American Association for the Study of Liver Disease in Boston, where results of a head-to-head study between Tykeza and Hepsera are scheduled for presentation.

Terms of Idenix's marketing collaboration call for a co-promotion arrangement with Novartis in the U.S., France, Germany, Italy, Spain and the UK. Idenix is taking the commercial lead in the U.S., where it has hired an unspecified number of sales representatives who are ready to launch Tyzeka once the FDA clears its marketing materials. Novartis' sales force will market the drug in the States, too.

Tyzeka's FDA approval did not trigger a milestone payment, but Idenix would receive such rewards upon European and Chinese clearances.

Basel, Switzerland-based Novartis, which is Idenix's majority shareholder, is taking the commercial lead in Europe and also is responsible for marketing and distribution in the rest of the world. The companies' 3-year-old relationship also extends to valtorcitabine and valopicitabine, the latter being Idenix's hepatitis C drug in Phase II.

On Thursday, Idenix's stock (NASDAQ:IDIX) rose 3 cents to $9.88, a day after adding 15 cents.