August 8, 2006 (AIDSmeds)—Tanox, a Houston-based pharmaceutical company, has been
instructed by the U.S. Food and Drug Administration (FDA) to complete
another round of preliminary clinical trials of its entry inhibitor TNX-355
before moving the drug into advanced studies. This requirement, the
company suggests, will likely mean a delay in the development and
ultimate approval of the drug.
According to a press
release distributed by Tanox on August 3rd, the FDA has informed the
company that TNX-355 has therapeutic potential. However, before it can
move into late-stage phase II and phase III clinical trials – which
Tanox was hoping to move forward with this year – the FDA has requested
that the company first conduct additional early-stage phase II studies
to determine the correct dose of the drug.
TNX-355 is a
monoclonal antibody – a genetically engineered protein that binds to
the CD4 receptor of T-cells. Once TNX-355 binds to these receptors, HIV
cannot successfully bind with the surface of T-cells, thus preventing
the virus from infecting them.
TNX-355 is injected
directly into the blood, through an IV line, once every two weeks. It
holds promise for HIV-positive people who have tried and failed other
HIV medications in the past given that it targets HIV differently than
most of the approved and other experimental options.
Results from a preliminary phase II study
were reported in May. The study enrolled 82 HIV-positive people who had
tried and failed other HIV drugs in the past. All of the patients
enrolled in the study received optimized background treatment – meaning
any 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 intravenously
every other week); the remaining one-third of the patients received
placebo.
After 48 weeks, treatment with the 10mg/kg dose of TNX-355 resulted in a viral load
reduction of 0.96 log. However, in the higher dose, which would be
expected to reduce viral load even more, the viral load only decreased
by 0.71 log. It is likely that questions surrounding the more limited
viral load response in the group receiving the higher dose of the drug,
compounded by the fact that only two doses have been tested in clinical
trials, sparked the FDA to require additional study data involving
different doses.
"I think this was an appropriate action
on the FDA's part," said Martin Delaney, Founding Director of Project
Inform in San Francisco. "They're doing their job. The data from the
Tanox trial raises a number of questions about the dosing of the drug
and it's far better to address them now than later. Going forward
without really knowing the right dose of a new drug is the most common,
and worst, mistake that fledgling companies make."
Tanox
said that it will be spending the next few weeks discussing clinical
trial options with the FDA. However, the company warned that additional
studies will likely delay the company's final application for drug
approval.
"Despite the potential delay in our
development program, we are encouraged that the FDA has recognized the
therapeutic potential of TNX-355 in HIV treatment-experienced
patients," said Danong Chen, Tanox's President and Chief Executive
Officer. "This patient population has a limited number of treatment
alternatives, and we continue to believe that TNX-355 could be a
valuable option for patients. We plan to work closely with the [FDA] on
a clinical trial design to identify the appropriate dose and dosing
regimen."
