Washington Editor

Partners Idenix Pharmaceuticals Inc. and Novartis Pharmaceuticals Corp. submitted telbivudine's new drug application with the FDA for chronic hepatitis B.

The application, for a 600-mg dose of the oral nucleoside analogue, represents the first of several filings to come - Novartis Pharma AG, Idenix's majority owner with a 56 percent stake in the Cambridge, Mass.-based firm, plans to file for the once-daily tablet's approval in the European Union and key Asian markets later this quarter.

The partners requested a six-month review from the FDA, which will decide in the next 60 days whether to accept the application.

"This is not so much the end of the line, but the end of a chapter for the clinical and regulatory groups," said Guy Macdonald, executive vice president of operations. "It's really a start of the road for the commercial people. It's exciting for us."

The NDA was submitted just seven years after Idenix filed a patent application on this use of telbivudine and is based primarily on one-year data from the GLOBE study, a two-year, Phase III trial still under way to compare telbivudine with standard therapy lamivudine (Combivir, from GlaxoSmithKline plc). Those top-line data showed telbivudine to be noninferior, the 1,367-patient study's one-year primary efficacy endpoint. (See BioWorld Today, Aug. 1, 2005.)

"Most other compounds in this category were also filed [for approval] with one-year data," explained Teri Dahlman, Idenix's manager of corporate communications.

Subsequent findings released two months ago at the American Association for the Study of Liver Diseases meeting demonstrated that telbivudine provided greater response on all evaluated virologic markers compared to lamivudine after one year, in both HBeAg-positive and HBeAg-negative patients with chronic hepatitis B. Specifically, significantly more telbivudine patients achieved clearance of detectable hepatitis B virus DNA (PCR negative). In HBeAg-positive patients, telbivudine treatment led to a loss of detectable hepatitis B virus DNA in 60 percent of patients compared to 40 percent among those on lamivudine.

"When you look at viral suppression or patients achieving viral clearance, we were superior to lamivudine," Dahlman told BioWorld Today. "So on all virologic or viral-related measures, telbivudine was superior to lamivudine at one year of treatment."

Data such as those help set telbivudine apart from other products in this area, and Macdonald told BioWorld Today that marketing efforts would focus on its ability to drive down viral loads "faster, earlier and with a [more] rapid response than we see with the others."

Additional products used in this space include Hepsera (adefovir, from Gilead Sciences Inc.), Viread (tenofovir, also from Gilead) and Baraclude (entecavir, from Bristol-Myers Squibb Co.). Also, because telbivudine specifically targets the viral DNA polymerase enzyme responsible for the hepatitis B virus' replication and is not active against other viruses that cause human disease, it can be used for treating co-infected patients without an increased risk of contributing to resistance development for HIV or other viruses.

"From a safety and convenience point of view, we really do believe that telbivudine has a really good profile," Macdonald said, "and is extremely competitive with the products that are out on the market."

The GLOBE study is the largest registration trial for a chronic hepatitis B treatment and the first worldwide trial to include clinical sites and patients in mainland China. In total, it has recruited participants in 112 sites in 20 countries. It ends in May, after which all patients will roll into a longer-term follow-up study.

Also, several other trials have gotten under way to expand telbivudine's profile, a clear benefit of Idenix's relationship with Basel, Switzerland-based Novartis, Macdonald said. One study is evaluating telbivudine compared to adefovir, another is testing various combination therapies and a third is looking at it in lamivudine-resistant patients, "so within the next year, we'll certainly have a very broad range of studies to supplement our filing," Macdonald added.

Estimates from the Centers for Disease Control and Prevention in Atlanta suggest that 1.25 million Americans are chronically infected with hepatitis B. Idenix's partnership with Novartis began nearly two years ago, at which time Novartis first took its majority stake in Idenix. The NDA filing does not trigger a milestone payment.

But the collaboration provides that both companies will co-promote telbivudine in the U.S., France, Germany, Italy, Spain and the UK. That arrangement also includes valtorcitabine (val-LdC), another investigational hepatitis B drug and other product candidates that Novartis has licensed. Novartis holds the exclusive license to commercialize telbivudine and valtorcitabine in the rest of the world. (See BioWorld Today, March 27, 2003.)

Macdonald said the partners could launch telbivudine within a few weeks of approval.

The deal also gives Novartis an exclusive option to license and collaborate on other product candidates in Idenix's portfolio, including valopicitabine (NM283) for chronic hepatitis C. If that antiviral gets through Phase II, Novartis can opt to license the compound for a potential $525 million, including clinical and regulatory milestones.

Last fall, Idenix priced a public offering worth $150 million, funds to be used for building working capital and supporting research and development into its infectious disease drug candidates. (See BioWorld Today, Oct. 27, 2005.)

On Tuesday, its stock (NASDAQ:IDIX) fell 18 cents to close at $16.93.