West Coast Editor

Landing another punch in the ever-tricky science of beating HIV, Gilead Sciences Inc. said the combination of Viread and Emtriva - approved a few weeks ago as Truvada - proved better in preliminary trial results than GlaxoSmithKline plc's Combivir, which consists of lamivudine and zidovudine in a single pill.

"That's an important data point, at least when it comes to how Truvada's going to be marketed," said William Tanner, analyst with Leerink Swann & Co. in New York. "They've got the wind at their back now."

Gilead's stock (NASDAQ:GILD) closed Thursday at $69.24, up $2.42.

The 24-week data are from Study 934, an ongoing Phase III, open-label, 48-week trial that enrolled 517 HIV-infected patients in the U.S. and Europe. The pre-specified intent-to-treat population includes 487 patients, with participants in one arm getting 300 mg of Viread (tenofovir disoproxil fumarate), 200 mg of Emtriva (emtricitabine), and 600 mg of efavirenz, all dosed once daily. Patients in the comparator arm are given Combivir twice daily and efavirenz 600 mg once daily.

Gilead is carrying out the combination trial by giving Viread and Emtriva as separate pills, since the combination was not available when the study started, "but you can go ahead and infer that the outcome would be the same. [Gilead] will continue to sell them individually" as well, Tanner added.

Patients entering Study 934 previously had not received antiretroviral therapy and had HIV RNA levels greater than 10,000 copies/mL. At 24 weeks, data show 88 percent of patients in the Viread/Emtriva arm compared to 80 percent of patients in the Combivir arm achieved and maintained HIV RNA levels less than 400 copies/mL, and the incidence of Grade 3 or Grade 4 clinical adverse events was 9 percent for the Viread/Emtriva arm, compared to 15 percent for the Combivir arm. Gilead expects to present those data at a scientific conference later this year.

"It's a non-inferiority study, but our consultants had told us they thought there would be a trend toward superiority," Tanner said.

The FDA approved single-tablet Truvada, a nucleoside reverse transcriptase inhibitor (nRTI), for once-per-day use in combination with other antiretroviral agents. Combivir, the nRTI from London-based GSK, gained marketing clearance in the U.S. in 1997. On the same day Truvada won approval, the agency also gave its nod to GSK's Epzicom, yet another combo pill, this one made up of abacavir and lamivudine. (See BioWorld Today, Aug. 2, 2004.)

Like Truvada, Epzicom is indicated for use in combination with other antiretroviral drugs from different classes, such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors for adults with HIV-1.

Gilead's 2004 guidance for its Viread/Emtriva/Truvada (V/E/T) franchise is $850 million to $875 million, but a survey of doctors by MEDACorp, a division of Leerink Swann, caused Tanner's firm to offer guidance of $920 million for the year.

"Physicians continue to project Truvada as leader in the combo nRTI market," Tanner wrote in his report.

There's more potential good news for Gilead. Gregory Wade, analyst with Pacific Growth Equities in San Francisco, said in a research note that the firm could benefit from stockpiling of the influenza drug Tamiflu (oseltamivir phosphate) that began at the outbreak of the bird flu in Asia at the end of last year. Gilead gets royalties on sales of the neuraminidase inhibitor from Hoffmann-La Roche Inc., of Nutley, N.J.

"Flu experts caution that it is only a matter of time before the next severe flu pandemic strikes, which could claim six times more lives than the regular flu, such as the 1918 pandemic that killed 20 million people worldwide," Wade wrote. "Tamiflu is one of the few drugs recommended to be used for preparedness against such potential severe flu pandemic."

Adding fuel to that potentially lucrative, if unsettling, fire was the U.S. Department of Health and Human Services' Pandemic Influenza Response and Preparedness Plan, released Thursday for public comment through October. The report mentions neuraminidase inhibitors specifically, noting that they bring fewer side effects than other drugs and appear less likely to induce resistance.

"The major issues with the neuraminidase inhibitors are their relatively high cost and limited availability," the report said, noting supplies are "extremely limited" of zanavir, which is sold as Relenza by GSK worldwide, as part of a deal with Biota Holdings Ltd., of Melbourne, Australia.

Since the supply of Tamiflu might also be limited - and held by "the private sector" - the plan recommended "stocks available in a pandemic should be targeted to priority groups with well-defined guidelines for prophylaxis and therapy" and tight collaboration between health care organizations and providers.

"I haven't seen the report, but [stockpiling] should benefit Gilead, because they get a low double-digit royalty on Tamiflu sales," Tanner said.

The bigger story, though, is the Study 934 results, which proved "better than [most] people expected. I think Gilead's in great shape," he said.

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