Assistant Managing Editor

Gilead Sciences Inc. and Bradmer Pharmaceuticals Inc. each moved compounds into late-stage testing, with Gilead starting the first of two Phase III trials of its HIV integrase inhibitor elvitegravir, while the Canadian firm began enrolling patients in its Phase III program of monoclonal antibody Neuradiab in brain cancer.

Gilead's elvitegravir (formerly GS 9137), a compound that Deutsch Bank analyst Mark Schoenebaum has called "potentially transformational" for the company, is designed with a once-daily dosing regimen that could give it a clear marketing advantage over the existing twice-daily integrase inhibitor marketed by Whitehouse Station, N.J.-based Merck & Co. Inc. as Isentress. Launched on the U.S. market following its October 2007 approval, Isentress recorded worldwide sales of $77 million for the second quarter.

The Phase III elvitegravir study is designed as a noninferiority trial, comparing elvitegravir, which is boosted by ritonavir, to Isentress (raltegravir) in treatment-experienced HIV patients at treatment centers in the U.S. and Puerto Rico.

A total of 700 patients who have documented viral resistance will be randomized 1-to-1 to receive either regimen plus background regimens - a fully-active ritonavir-boosted protease inhibitor and a second agent that might include a nucleoside reverse transcriptase inhibitor, etravirine, maraviroc (Selzentry, Pfizer) or enfuvirtide (Fuzeon, Trimeris and Roche) - and the primary endpoint will be the proportion of patients in both arms who achieve and maintain confirmed viral load of less than 50 copies/mL through 48 weeks.

The noninferiority design marks a different approach from the company's earlier Phase II study, which demonstrated promising results last year. That study compared ritonavir-boosted elvitegravir to a boosted protease inhibitor (usually darunavir or tipranavir) in combination with an optimized background regimen.

Results from that study showed elvitegravir to be statistically superior in reducing viral load in treatment-experienced patients, and 92 percent of patients on the highest dose of 125 mg had a greater than 1 log viral load reduction at 24 weeks compared to 61 percent of patients in the control arm. (See BioWorld Today, March 5, 2007.)

Gilead representatives could not be reached for comment.

Unlike typical antiviral drugs, Integrase inhibitors aim to work by interfering with HIV replication by blocking the virus' ability to integrate into a cell's genetic material. Gilead, of Foster City, Calif., picked up worldwide rights, except for Japan, to elvitegravir through a 2005 deal with Tokyo-based Japan Tobacco Inc.

Secondary endpoints of the Phase III study include additional efficacy measures, as well as safety and tolerability data.

A second Phase III study involving 700 treatment-experienced patients in Europe, Canada and Australia is expected to start later this year. Gilead said that trial will be conducted with a similar design to the U.S. study.

Earlier in its HIV pipeline, Gilead is working on GS 9350, a pharmacokinetic-enhancing compound that could be formulated as a boosting agent for elvitegravir to replace the need for ritonavir. The company's goal is eventually to formulate a combination product of GS 9350, elvitegravir and Truvada (emtricitabine and tenofovir disoproxil fumarate) into a single tablet. GS 9350 currently is in Phase I testing in healthy volunteers.

Gilead, which reported first quarter net income of $477 million, or 49 cents per share, had about $2.9 billion in cash and marketable securities as of June 30.

The company's shares (NASDAQ:GILD) gained $1.60 Wednesday to close at $52.70.

Neuradiab Begins Phase III in Brain Cancer

Moving ahead with its own pivotal program, Toronto-based Bradmer initiated enrollment in its Phase III trial of Neuradiab, a monoclonal antibody conjugated to Iodine-131, in front-line primary glioblastoma multiforme.

The GLASS-ART (GMB Locoregional Agent Survival Study - Antitenascin Radiolabeled antibody Therapy) study is designed to measure the survival benefit derived from adding Neuradiab to standard-of-care therapy, which consists of surgery, radiation and adjuvant chemotherapy (temozolomide), in patients diagnosed with primary GBM. The trial is expected to enroll up to 760 patients.

Neuradiab is believed to work by targeted tenascin, a protein expressed in about 99 percent of GBM cells but not in normal brain cells, the company said. The drug is delivered directly into the surgical resection cavity and is designed to deliver a concentrated level of radiation specifically to the remaining cancer cells. In earlier trials, patients treated with the Neuradiab therapy regimen showed survival benefits that significantly exceeded historical controls.

Bradmer, which has not yet posted second-quarter earnings, had a net loss of $3.2 million, or 23 cents per share, for the first quarter and ended that three-month period with $16.7 million in cash.

Bradmer shares (TSX:BMR) closed at C$1.14 (US$1.13) Wednesday, up 14 cents.