HIV patients gained another treatment option yesterday as the FDA signed off on Emtriva, a once-daily capsule for HIV from Gilead Sciences Inc.

The agency approved a 200-mg dose of the nucleoside reverse transcriptase inhibitor to be used in combination with other antiretroviral medications. Emtriva (emtricitabine) attacks the virus by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA. By interfering with that process, Emtriva is designed to help lower a patient's viral load and increase the number of T cells or CD4 cells.

The Foster City, Calif.-based company acquired the drug last year in its purchase of Triangle Pharmaceuticals Inc., which developed it under the name Coviracil. The $464 million acquisition bolstered Gilead's HIV stable, which already included a marketed drug, Viread (tenofovir disoproxil fumarate). (See BioWorld Today, Dec. 5, 2002.)

"We think this is a particularly important option because it's a once-daily drug, which is an issue very important to physicians and patients because many older HIV drugs need to be dosed as multiple pills, multiple times a day," Amy Flood, a Gilead spokeswoman, told BioWorld Today. "Another important characteristic for HIV is its tolerability; a big part of patients being able to stay on their regimen is being able to tolerate it. The side effect profile of this drug may help patients adhere to their treatment."

Earlier last year, Durham, N.C.-based Triangle, now a wholly owned subsidiary of Gilead, regained rights to the drug from Abbott Laboratories. The compound was part of a potential $335 million deal with the Abbott Park, Ill.-based firm that began four years ago. (See BioWorld Today, June 4, 1999, and Aug. 1, 2002.)

Triangle, which filed for Emtriva's approval in November, originally licensed the compound in 1996 from Emory University in Atlanta. The FDA's authorization marks Gilead's third drug approval in less than two years.

And because the company already operates in the HIV marketplace with Viread, a one-tablet, once-daily nucleotide reverse transcriptase inhibitor that generated $225.8 million in global sales revenue last year and is expected to produce $475 million to $500 million this year, a marketing synergy is firmly in place.

"We have rights both in the U.S. and Europe, so we will commercialize it ourselves," Flood said, adding that average Wall Street estimates peg 2003 sales of Emtriva to reach just north of $14 million. Flood declined to make further projections. In the U.S., Gilead said wholesalers would pay $252.83 for a bottle of 30 capsules of Emtriva, about one month of therapy. The company plans to begin shipping the drug in the next week.

An application for European approval of Emtriva for HIV was submitted in December, and Gilead said it expects the overseas evaluation to be completed next year.

The company is developing a fixed-dose co-formulation of Emtriva and Viread. Viread was approved in October 2001. Gilead said the combination product could be available by early 2005. (See BioWorld Today, Oct. 30, 2001.)

"We think there is a natural partnership there, and the drugs will be used together now, before the availability of the co-formulation," Flood said, adding that the FDA might not require clinical studies of the co-formulation. "We would do a bioequivalence study to make sure the two drugs in one pill act the same as the two drugs separately."

Gilead also is planning a clinical trial to compare Viread and Emtriva to another co-formulated product, Combivir (zidovudine and lamivudine, from GlaxoSmithKline plc, of London). Both regimens also will include efavirenz. Flood said Gilead expects to begin enrollment before the end of the year.

Emtriva's approval was bolstered by data from studies in treatment-naive and treatment-experienced HIV patients.

In a Phase III trial of 571 patients who had not taken HIV drugs before, 81 percent of the 286 receiving Emtriva in combination with other antiretroviral drugs experienced a reduction in HIV RNA below 400 copies/mL and 78 percent experienced a reduction below 50 copies/mL. In the 285-patient comparator arm, the data showed equivalent reductions in 68 percent and 59 percent of patients, respectively.

In a Phase III study of 440 treatment-experienced patients, Emtriva achieved comparable HIV suppression in patients previously treated with lamivudine. Findings showed that 77 percent of 294 patients treated with Emtriva in combination with other antiretroviral drugs achieved a reduction in viral load below 400 copies/mL and 67 percent achieved below 50 copies/mL vs. 82 percent and 72 percent, respectively, in the 146-patient control arm.

Beyond HIV, Gilead is studying the compound in a Phase III trial for chronic hepatitis B. The company already markets Hepsera (adefovir dipivoxil 10 mg) in that indication. Its other marketed products include AmBisome (liposomal amphotericin B), Tamiflu (oseltamivir phosphate) for influenza, Vistide (cidofovir) for cytomegalovirus retinitis in AIDS patients, and DaunoXome (liposomal daunorubicin) for AIDS-related Kaposi's sarcoma.

Elsewhere in its pipeline, Gilead is developing Amdoxovir, a nucleoside analogue for HIV also acquired from Triangle that is in Phase II development. The company has advanced a prodrug of tenofovir into a Phase I/II study for its technology. Still in preclinical development is a protease inhibitor that Flood said Gilead expects to push into the clinic early next year.

Gilead's stock (NASDAQ:GILD) gained $1.36 Wednesday to close at $56.36.