Washington Editor

Vertex Pharmaceuticals Inc. and partner GlaxoSmithKline plc won FDA approval of Lexiva, an HIV protease inhibitor that can be dosed once or twice daily, with or without food and water restrictions.

The partners expect to launch Lexiva (formerly 908 or GW433908) in November. Vertex and GSK co-discovered Lexiva, a calcium phosphate ester prodrug of their Agenerase (amprenavir).

While the HIV market includes a number of other protease inhibitors, Joshua Boger, chairman and CEO of Cambridge, Mass.-based Vertex told BioWorld Today Lexiva offers patients and doctors advanced features that earlier, first-generation drugs just don't provide.

"Increasingly, HIV is being viewed as a chronic condition that is manageable if you can just stay on the treatments," Boger said. "The idea of having symmetrical dosing in which you put together a combination of drugs so they are dosed in the same way - that kind of symmetry or simplicity of dosing is what keeps people on drug therapy, and in HIV, that's the name of the game."

Furthermore, other marketed products impose eating and drinking restrictions, Boger said, adding: "You'd be surprised at some of the restrictions. One of the leading protease inhibitors has to be taken twice a day with a high-fat meal, and a McDonald's cheeseburger and fries don't qualify - they are not high-fat enough."

Patients will take two to four Lexiva pills a day. By comparison, people on Agenerase take eight to 16 pills a day. Indeed, that is one reason Vertex and GSK believe most Agenerase patients will convert to Lexiva.

"How long that takes and how aggressively GSK will devote resources to that conversion vs. getting new patients into treatment remains to be seen," Boger said. "I think eventually Agenerase will leave the market, but it won't happen instantly."

According to GSK's guidance for 2003, worldwide sales of Agenerase are expected to reach $60 million. Boger said the companies have not provided specific guidance for Lexiva, but "we expect it to build to be an important part of the HIV protease inhibitor market, which is $1.6 billion worldwide."

A research note by Phil Nadeau, analyst with SG Cowen Securities Corp. in New York, said despite Lexiva's flexible dosing and low pill burden, the new protease inhibitor is not expected to unseat Kaletra (Abbott Laboratories) as the market leader in the class. Lexiva will sell for about $8 a pill, resulting in a cost of $7,092 per year for the boosted regimen, or $11,680 a year for the un-boosted. Kaletra (a boosted regimen) is priced at $6,847 a year, the note said.

Per the financial agreement with GSK, Vertex will receive 15 percent to 20 percent on Lexiva sales in the U.S. and the European Union. (EU approval is expected in early 2004.)

Vertex owns all rights in most Asian territories and has yet to decide whether it will seek a partner for those areas.

Over the life of the Lexiva deal, GSK has paid Vertex $47 million in milestones, up-front fees and research payments. U.S. approval triggers a $2.5 million milestone payment from GSK. A similar payment would be due on European approval.

Despite those payments, Boger said Vertex's main economic benefit is in royalties. Nadeau's note said the royalties will be in the mid-to-high teens.

"This partnership with GSK in HIV protease inhibitors is perhaps one of the most successful research and development partnerships ever between a biotech and pharmaceutical company," Boger said. "This is our second approved drug from a research collaboration that is targeted only in a single disease and only in a single target in that disease, and we have a third compound in development. Vertex and GSK are extremely committed to bringing important new treatments forward in HIV, and so far, we've been very successful in doing that."

More than 1,200 people, both antiretroviral therapy-na ve patients and protease inhibitor-experienced patients participated in the three Phase III trials to test the safety and efficacy of Lexiva with and without ritonavir. In all three trials, study drugs were taken as part of combination therapy that included two nucleoside reverse transcriptase inhibitors.

The open-label Phase III CONTEXT study evaluated 300 treatment-experienced patients at 80 centers worldwide. CONTEXT compared once-daily and twice-daily dosing of Lexiva in combination with ritonavir to lopinavir/ritonavir (Kaletra). (See BioWorld Today, Oct. 25, 2002.)

CONTEXT did not hit the 48-week primary endpoint of non-inferiority to the comparator drug. However, Boger on Tuesday told BioWorld Today the trial was not large enough to net a definitive conclusion. He also said the FDA did not classify the trial as a failure, as 58 percent of patients receiving Lexiva achieved undetectable viral load, compared to 61 percent of patients taking lopinavir/ritonavir.

Two other Phase III studies, NEAT and SOLO, which included 249 and 660 patients, respectively, compared 908 to nelfinavir (Viracept, from Pfizer Inc.). In NEAT, 66 percent of patients taking Lexiva achieved undetectable viral load, compared to 52 percent of patients in the nelfinavir arm. And in SOLO, 69 percent of patients taking Lexiva achieved undetectable viral load compared with 68 percent of patients in the nelfinavir arm. Both studies met their primary endpoints at 24 and 48 weeks. (See BioWorld Today, May 20, 2002; Sept. 30, 2002; and Feb. 18, 2003.)

Vertex's stock (NASDAQ:VRTX) rose 54 cents Tuesday to close at $13.57.