August 8, 2006 (AIDSmeds)—Tanox, a Houston-based pharmaceutical company, has beeninstructed by the U.S. Food and Drug Administration (FDA) to completeanother round of preliminary clinical trials of its entry inhibitor TNX-355before moving the drug into advanced studies. This requirement, thecompany suggests, will likely mean a delay in the development andultimate approval of the drug.

According to a pressrelease distributed by Tanox on August 3rd, the FDA has informed thecompany that TNX-355 has therapeutic potential. However, before it canmove into late-stage phase II and phase III clinical trials – whichTanox was hoping to move forward with this year – the FDA has requestedthat the company first conduct additional early-stage phase II studiesto determine the correct dose of the drug.

TNX-355 is amonoclonal antibody – a genetically engineered protein that binds tothe CD4 receptor of T-cells. Once TNX-355 binds to these receptors, HIVcannot successfully bind with the surface of T-cells, thus preventingthe virus from infecting them.

TNX-355 is injecteddirectly into the blood, through an IV line, once every two weeks. Itholds promise for HIV-positive people who have tried and failed otherHIV medications in the past given that it targets HIV differently thanmost of the approved and other experimental options.

Results from a preliminary phase II studywere reported in May. The study enrolled 82 HIV-positive people who hadtried and failed other HIV drugs in the past. All of the patientsenrolled in the study received optimized background treatment – meaningany combination of approved HIV medications – based on the results of drug-resistance testing.Two-thirds of the patients also received one of two doses of TNX-355(10mg or 15mg per kilogram of body weight administered intravenouslyevery other week); the remaining one-third of the patients receivedplacebo.

After 48 weeks, treatment with the 10mg/kg dose of TNX-355 resulted in a viral loadreduction of 0.96 log. However, in the higher dose, which would beexpected to reduce viral load even more, the viral load only decreasedby 0.71 log. It is likely that questions surrounding the more limitedviral load response in the group receiving the higher dose of the drug,compounded by the fact that only two doses have been tested in clinicaltrials, sparked the FDA to require additional study data involvingdifferent doses.

“I think this was an appropriate actionon the FDA’s part,” said Martin Delaney, Founding Director of ProjectInform in San Francisco. “They’re doing their job. The data from theTanox trial raises a number of questions about the dosing of the drugand it’s far better to address them now than later. Going forwardwithout really knowing the right dose of a new drug is the most common,and worst, mistake that fledgling companies make.”

Tanoxsaid that it will be spending the next few weeks discussing clinicaltrial options with the FDA. However, the company warned that additionalstudies will likely delay the company’s final application for drugapproval.

“Despite the potential delay in ourdevelopment program, we are encouraged that the FDA has recognized thetherapeutic potential of TNX-355 in HIV treatment-experiencedpatients,” said Danong Chen, Tanox’s President and Chief ExecutiveOfficer. “This patient population has a limited number of treatmentalternatives, and we continue to believe that TNX-355 could be avaluable option for patients. We plan to work closely with the [FDA] ona clinical trial design to identify the appropriate dose and dosingregimen.”