Staff Writer

Montreal-based Theratechnologies Inc. might well be on its way to commercialization of its lead compound, tesamorelin, in patients with HIV-associated lipodystrophy, thanks to positive 26-week data from its second Phase III trial of the drug.

In addition to meeting its primary endpoint in the study, defined as reduction in visceral adipose tissue (VAT), tesamorelin met four secondary endpoints.

The Phase III trial was part of a special protocol assessment agreed upon by the company and the FDA.

Data from the first Phase III trial using tesamorelin were published in the Dec. 6, 2007, issue of the New England Journal of Medicine and showed that the drug improved excess visceral fat in HIV-infected patients with lipodystrophy, a disorder characterized by the accumulation of adipose tissue around primary organs. Top-line data were reported in 2007. (See BioWorld Today, Oct. 2, 2007.)

But in order to push the product to market, the FDA requested that Theratechnologies conduct another Phase III trial to confirm the drug's efficacy.

Andrea Gilpin, the company's vice president of investor relations and communications, told BioWorld Today that while "the most significant take-away from the trials is that we met the clinical endpoints in both of our Phase III trials," more importantly, the Phase III data give the company the green light to proceed toward the filing of a new drug application.

In the trial, a total of 404 patients were treated in North America and Europe. The two-arm study was powered to detect an 8 percent reduction in VAT vs. placebo. Patients treated with tesamorelin for 26 weeks achieved an average 11 percent decrease in VAT compared to baseline and an average 10 percent decrease in VAT compared to placebo. Moreover, the average VAT reduction was -20.6 square centimeters. Body fat was preferentially lost in the visceral cavity, with no significant changes in subcutaneous adipose tissue.

A buildup of VAT, which can be caused not only by HIV, but also by medications used to treat the disease, is dangerous particularly because it affects major organs, such as the heart, liver and kidneys. Indeed, Gilpin described lipodystrophy as "a collateral disease to HIV."

Lipodystrophy can increase a patient's risk for heart attacks and cardiovascular events in general.

But Gilpin said that tesamorelin appears to be effective in reducing VAT without modifying subcutaneous fat in the body. "What our drug does is reduce that bad fat, without having any effect on diabetes," she said, noting that some HIV patients are diabetic or pre-diabetic, so in treating VAT accumulation, it is important not to modify patient glucose and subcutaneous adipose tissue levels.

And the drug has proved safe in Phase III studies. Results showed no clinically significant differences between the tesamorelin-treated group and placebo in glycemic control. Adverse events with an incidence of more than 10 percent included injection site redness, injection site itchiness and joint pain. The dropout rate for the patients treated with tesamorelin was 25 percent compared to 27 percent for the placebo group.

In addition, Gilpin said that the study showed tesamorelin's effectiveness in achieving other endpoints. "The study met its primary endpoint as well as the important secondary endpoints."

Results demonstrated that treated patients significantly improved their belly appearance distress compared to the placebo group, which Gilpin said was an important secondary endpoint because of its implications for patient adherence to HIV regimens. According to Gilpin, HIV patients often find it difficult to maintain a treatment regimen, and improving their body image could positively shape their attitudes toward therapy.

With respect to lipid profiles, a trend for improvement in triglyceride levels was recorded for the treated group and was significantly different vs. baseline. However, there was no significant impact on the total cholesterol to HDL cholesterol ratio.

Moreover, IGF-1 mean levels were within physiological range and increased by 73 percent when compared to placebo.

Despite meeting all of those endpoints, the company is conducting a 26-week extension of the study. "For ethical reasons, those patients that were on placebo must be crossed over to drugs," Gilpin said. All placebo patients who elect to continue treatment will receive tesamorelin from weeks 26 to 52.

Gilpin said that of the treated group from the first 26 weeks, another subset will be switched to placebo. "In that case, we want to confirm the results we released in October 2007, that once you withdraw the drug, the effect is fairly rapidly lost."

Despite the extension, the company hopes to put together its NDA in the near future. "We're now going to assemble the documentation required for submission of the NDA, which is considerable, and we expect to file at the end of this year or at the very early part of next year," Gilpin said.

Following that timeline, she said Theratechnologies hopes tesamorelin will be approved for market 10 months after its NDA submission.

Overall, Gilpin said the company is quite optimistic about tesamorelin's potential in that indication, but added that it could pursue other indications for the drug.

"We have a couple of studies being conducted through NIH off-site," she said. "And we hope to disclose a second clinical program for tesamorelin toward the end of this year."

Shares of Theratechnologies (TSX:TH) closed at C$6.39 (US$6.28), down C5 cents.