Washington Editor

Theratechnologies Inc. reported that 52-week results of tesamorelin (TH9507) in patients with HIV-associated lipodystrophy not only supported the 26-week safety data, but showed that patients taking the product long term had better outcomes.

Patients treated with tesamorelin for 26 weeks lost 15 percent of their visceral adipose tissue (VAT) - a risk factor for cardiovascular disease and Type II diabetes - while those treated for 52 weeks experienced a total reduction of 18 percent VAT.

HIV-associated lipodystrophy is a complication associated with the long-term use of antiretroviral therapy for the HIV infection. The syndrome, which affects about 250,000 people in North America and Europe, is manifested as body composition changes, including the accumulation of abdominal fat - primarily as visceral fat - loss of extremity and subcutaneous fat and interrelated metabolic abnormalities, such as blood-lipid disorders and insulin resistance.

There are no current therapies on the market to treat HIV-associated lipodystrophy. Tesamorelin, a stabilized analogue of the growth hormone releasing factor, is aimed at reducing VAT in lipodystrophy patients.

The Phase III trial of tesamorelin enrolled 412 patients in a multicenter, double-blind, randomized, placebo-controlled study conducted in 43 centers in the U.S. and Canada. The study examined the safety and efficacy of a daily administration of 2 mg of the drug for 26 weeks and long-term safety over 52 weeks. The primary endpoint was a reduction VAT.

During a conference call Monday, Theratechnologies CEO Yves Rosconi said that the Phase III study was the "largest trial to be conducted ever in a lipodystrophy patient population."

He noted that the 52-week expansion study included three main treatment arms: a treatment group that crossed over to placebo at 26 weeks, a placebo group that crossed over to receive therapy at 26 weeks and a group that received the therapy for the entire 52 weeks.

However, Rosconi explained, there was no patient group that was on placebo for the entire 52 weeks, and therefore, there was no direct comparator for the group of patients that were treated for 52 weeks.

The 52-week results, he said, showed that the safety profile of the drug was "virtually unchanged" from the data observed after 26 weeks of treatment, which was reported in December 2006.

No issues related to glycemic control were observed in patients after 52 weeks of treatment, Rosconi said.

Results of the treated placebo arm indicated that patients regained their VAT to almost baseline levels within six months of discontinuation of treatment, he noted.

"These data suggest that continuous exposure to tesamorelin is required for maintenance of VAT reduction," Rosconi asserted.

The dropout rate for the group that received therapy for 52 weeks was 16 percent compared with 23 percent for the group that received treatment over the first 26 weeks, Rosconi noted.

Only 2.6 percent of participants discontinued treatment due to adverse events in the group that received therapy for 52 weeks, which, compares favorably to a discontinuation rate associated to adverse events of 12.1 percent within the group that received therapy during the first 26 weeks, he said.

Higher rates of arthralgia, or joint pain, were observed during the first 26 weeks of treatment (13.6 percent) compared with rates reported at the end of 52 weeks (4 percent), Rosconi said.

Two deaths occurred during the extension phase of the study, he noted. However, the principal investigators, the FDA and the independent data safety monitoring board declared that neither death was related to tesamorelin use, Rosconi said.

An autopsy confirmed that one of the participant deaths was attributed to arteriosclerosis, and the second participant died from post-surgical complications, Rosconi explained. "As a whole, the safety profile is very promising for use in HIV-associated lipodystrophy," he said. "All side effects were manageable. There were no surprises and no new adverse events reported at 52 weeks, suggesting that long-term administration of tesamorelin is well tolerated by these patients. We see these results as clearly positive, attesting to the efficacy and safety of tesamorelin."

Montreal-based Theratechnologies plans to present a more detailed analysis of the Phase III study at the 11th European AIDS Conference Oct. 26 in Madrid, Spain, Rosconi said. From a clinical perspective, he added, the 52-week results "lend themselves to a very attractive product profile for long-term treatment of patients with lipodystrophy."

"Given these attributes, we see ourselves as leaders now in the field of lipodystrophy, with an extremely competitive product," Rosconi said.

He said his firm is preparing to "gear up toward commercialization" of tesamorelin. However, he noted, Theratechnologies must first complete a second Phase III trial to confirm the results of the first trial before submitting an approval application to the FDA.

Theratechnologies Sept. 4 announced that it had ended recruitment for its confirmatory Phase III trial of tesamorelin. "The rate of enrollment is one and a half months faster than our first pivotal Phase III trial," Rosconi said, adding that his firm expects an "exciting year ahead in the clinic."

Before the end of 2007, he said, Theratechnologies plans to announce a second indication for tesamorelin.

The company also plans to soon release updated figures for the lipodystrophy market, he added. "We believe these milestones will substantially advance our business plan and continue to create significant value for Theratechnologies' shareholders," Rosconi said.