West Coast Editor

Favorable data from the ongoing Phase II trial with its entry inhibitor against HIV pushed Tanox Inc.'s stock up 11.6 percent, as TNX-355 proved in a 24-week study that it knocked down viral load when combined with optimized background therapy (OBT) - an outcome that "further positions [the drug] as the first monoclonal antibody to treat HIV," noted Nancy Chang, president and CEO of Houston-based Tanox, during a conference call.

The company's stock (NASDAQ:TNOX) closed Wednesday at $13.95, up $1.46, after trading as high as $14.70.

Specifically, the study met its primary endpoint with TNX-355 plus OBT demonstrating a statistically significant reduction in viral load compared to placebo plus OBT at week 24. Patients were randomized to get 10 mg/kg, 15 mg/kg or placebo every two weeks, with those in the first group given a loading dose of 10 mg/kg every week for eight weeks.

The study was not designed to compare the two treatment arms to one another, so it's not possible to reach a "definitive conclusion" in that regard, Chang said. The study will continue to 48 weeks, and an end-of-Phase II meeting with the FDA is expected in early 2006.

In the results available so far, treatment with the 10 mg/kg dose of TNX-355, a humanized monoclonal antibody, resulted in a viral-load reduction of 1.16 log¹⁰, compared with a 0.20 log¹⁰ reduction in the placebo group, which is a 0.96 log¹⁰ greater reduction (p<0.001) in viral load in the analysis of the last observation carried forward.

Tanox said the reduction was maintained even with the more conservative method of analysis, in which patients without a week-24 value had their baseline value assigned instead of carrying the last observation forward. In this analysis, treatment with the 10 mg/kg dose of TNX-355 yielded a viral-load reduction of 1.19 log¹⁰, compared with a 0.32 log¹⁰ reduction in the placebo group, which is a 0.87 log¹⁰ greater reduction (p=0.002) in viral load.

The mean maximum viral-load reduction from baseline during the 24-week period in the 10 mg/kg dose arm was 1.97 log¹⁰ (p=0.002).

With the 15 mg/kg dose of TNX-355, results were a viral-load reduction of 0.95 log¹⁰, compared with a 0.20 log10 reduction in the placebo group (p=0.003), a 0.75 log¹⁰ greater reduction in viral load in the last observation carried forward analysis.

Key secondary endpoints included the proportion of subjects achieving a viral-load reduction of at least 0.5 log¹⁰, as well as those achieving a viral-load reduction of at least 1.0 log¹⁰, and the mean change in CD4+ cell count from baseline.

In the 10 mg/kg dose arm, 56 percent of patients recorded a viral-load decrease of at least 0.5 log¹⁰ at week 24, showing the durability of the reduction, and 44 percent had a viral-load decrease of at least 1.0 log¹⁰ at week 24. A mean CD4+ cell count increase was observed in all arms of the study, but was not significantly different between the treatment groups and placebo.

Both doses of TNX-355 were safe and well tolerated, with no severe adverse events or laboratory abnormalities related to the drug and no infusion-site reactions, the company said.

Stanley Lewis, Tanox's medical director for TNX-355, told investors the company has "given considerable thought" to dosing in a Phase III trial, but hasn't decided on the best.

"All of these data have just come in, and we are processing them feverishly," he said, adding that the firm is "committed to a once-every-two-weeks dosing scheme," which patients and physicians seem to find acceptable.

"We will proceed with that at least initially, and then explore other options, perhaps in a Phase IV study," Lewis said. As for the infusion time, it's 30 minutes now, but the company has "some flexibility" with that. Intravenous will stay the chosen route of administration, he added.

"This is really a large dose of antibody to try to give subcutaneously," Lewis said. "We are familiar with the other entry inhibitor [Fuzeon] that is on the market, and some of the difficulty with infusion-site reactions, as well as frequency of administration. We really want to stick with our I.V. infusion format for now."

Morrisville, N.C.-based Trimeris Inc.'s Fuzeon (enfuvirtide) is partnered with Basel, Switzerland-based F. Hoffmann-La Roche Ltd.