Washington Editor

Vertex Pharmaceuticals Inc.'s partner, GlaxoSmithKline plc, filed applications for approval in the U.S. and Europe for GW433908, an investigational HIV protease inhibitor co-discovered by the companies.

The product, which has not been assigned a name and is commonly referred to as 908 or VX-175, has performed well in three large clinical trials of 1,100 patients, Tony Coles, Vertex's senior vice president of commercial operations, told BioWorld Today.

"We think 908 is going to provide an important therapeutic option for HIV patients and physicians," Coles said. "We think it is going to be important because this compound has special efficacy in the higher-viral-load patients, who tend to be sicker. The fact that this can be given once or twice daily and is only two tablets, once or twice daily, is also going to be an important contribution. Right now, the competitors are three to five tablets, two or three times a day. So you look at a population that has to take a number of medications, this convenience feature is important in improving quality of life."

Coles explained that as a protease inhibitor, 908 actually reduces viral replication, consequently lowering the amount of virus circulating in the blood. "Clearly it is not a cure, but 908 is designed to interrupt the progression of the disease and to inhibit the replication of the virus."

A discovery of Vertex, of Cambridge, Mass., and GlaxoSmithKline (GSK), of London, 908 is a prodrug of Agenerase (amprenavir), an approved protease inhibitor co-marketed by the companies. "But 908 is a brand new compound that has a profile that in many ways has all the good that Agenerase has, but has a potency and convenience which will be far better," Coles said.

The submissions for registration include data from treatment-na ve and treatment-experienced patients who have participated in Phase III trials to evaluate the safety and efficacy of 908 in comparison with two widely used HIV protease inhibitors. The product was dosed as two tablets in both once-daily and twice-daily regimens, according to the company.

In October, Vertex released positive data from its open-label Phase III called CONTEXT, in which 300 treatment-experienced patients were studied at 80 centers worldwide. CONTEXT compared once-daily and twice-daily dosing of 908 in combination with ritonavir to lopinavir/ritonavir (Abbott Laboratories' Kaletra). Coles said 908 hit the 24-week endpoint, but the company hasn't given guidance as to when the 48-week data will be ready. (See BioWorld Today, Oct. 25, 2002.)

Meanwhile, 908 hit its endpoints at 24- and 48-week intervals in the two other Phase III trials called NEAT (study 30001) and SOLO (Study 30002). (See BioWorld Today, Sept. 30, 2002, and May 20, 2002.)

Last week's filings triggered a milestone payment from GSK to Vertex. "The milestone is within the guidance that we've given to Wall Street, but we don't typically divulge the specific amount," Coles said.

Regarding the timeframe expected to get 908 to market, Coles said the FDA hasn't determined whether 908 will be reviewed under the six-month priority guidelines or the 10-month traditional review.

GSK and Vertex will co-promote 908 in the U.S. and key markets in Europe.

Vertex's stock (NASDAQ:VRTX) closed Friday at $16.67, up 6 cents.