Washington Editor

Having gotten the "green light," Theratechnologies Inc. said it now has outlined pivotal plans for ThGRF (TH9507), its lead product for HIV-associated lipodystrophy, following a meeting with the FDA earlier this week.

"We have proven good [Phase II] results, and this was the basis to establish the company's strategy to move ahead," said Theratechnologies President and CEO Yves Rosconi, adding that the company chose the growth hormone-releasing factor (GRF) analogue as its primary product long after the business was founded about a dozen years ago.

As a result, the Montreal-based company plans to conduct a pair of Phase III trials in patients with the metabolic syndrome, which is characterized by changes in distribution of adipose tissue, dyslipidemia and glucose intolerance. The first study, which will include about 400 patients, is expected to begin by the middle of the year. It will be held primarily in the U.S., but will include a few sites in Canada. The trial will evaluate a 20-mg dose compared to placebo in a randomized, double-blinded setup, and eventually will be followed by a confirmatory study expected to follow the same protocol.

The FDA also agreed to use a reduction in visceral adipose tissue (VAT) as the primary endpoint. Secondary endpoints include lipid measures and body self-image. The agency also accepted the company's proposed inclusion of glucose-intolerant and diabetic patients in the study, who Rosconi said make up about 35 percent to 40 percent of HIV patients with lipodystrophy, with careful monitoring of glycemic control. A competitor's product, already in Phase III, is not testing such diabetic patients.

Theratechnologies' decision to move ThGRF forward follows a Phase II program that tested the product in more than 600 patients. Various data demonstrated that it safely induced increases in muscle mass with trends for functional improvement, lowered visceral fat reduction, improved lipid profiles, stimulated the immune system and enhanced daytime alertness.

"With VAT as the primary endpoint in Phase II, we had a statistically significant reduction vs. placebo," Rosconi told BioWorld Today. "We've shown against baseline a significant reduction, which was interesting and in line with other parameters we were checking."

The Phase III program will include an extension period of about a year to confirm the product's safety.

ThGRF induces the production and secretion of growth hormone in a specific, physiological, controlled and pulsatile fashion. Over the past few years, the company has identified a number of indications in which the product might find use, and by the end of the year expects to announce a direction in which to evaluate ThGRF beyond HIV-associated lipodystrophy.

"The net effect of our product is to release growth hormone," Rosconi said of its pulsatile properties, but "into a very different pattern," which differentiates it from growth hormone. It also gives advantages in safety and side effect profile, he said.

Eventually, Theratechnologies expects the product to enter an HIV-associated lipodystrophy market estimated at several hundred million dollars. There are no treatments approved for HIV-associated lipodystrophy, though the company noted that some new HIV therapies have shown signs of improving metabolic components of the disease, such as the accumulation of visceral fat and related complications.

"Our plan is to carry its development all the way to a new drug application," Rosconi said. "We've got a sufficient amount of funding to do that, for the two Phase III studies, and if we have to find a partner that would add value for our shareholders, we will consider it. But at the moment, we would like to play our options to create maximum value."

He added that Theratechnologies has about C$58 million (US$48 million) in cash reserves.

Potential competition includes Serono SA's Serostim, which the Geneva company advanced into Phase III last summer. While its timeline is more advanced, Rosconi noted that ThGRF could reach more patients, since it will be tested in diabetic patients, a population not included in Serostim's development.

Theratechnologies' other clinical programs in the fields of endocrinology and metabolism are investigating wasting associated with chronic disease and Type II diabetes. For diabetes, a recent Phase I study of a GLP1 analogue produced positive safety results, and the company is assessing which molecule from the program to advance. Other drugs for diabetes remain in preclinical development, including a program focused on an undisclosed target that is partnered with Johnson & Johnson, of New Brunswick, N.J.

"We are well balanced," Rosconi said, "with some early and some later-stage drugs as we speak."

On Thursday, its shares (TSE:TH) gained C26 cents, or 16.3 percent, to close at C$1.86.