Central fat accumulation is one manifestation of the lipodystrophy syndrome seen in some people with HIV, and it may increase the risk of cardiovascular problems. Recombinant human growth hormone has been shown to improve fat accumulation, but it can cause adverse side effects including blood glucose elevation, fluid retention, and carpal tunnel syndrome.

Theratechnologies' synthetic growth hormone-releasing factor tesamorelin (TH9507) appears to offer similar benefits with fewer side effects, since it stimulates the pituitary gland to release growth hormone in pulses (as happens naturally over the course of a day), bringing levels within the normal physiological range. Researchers reported promising 26-week interim results from a Phase 3 study of tesamorelin at the Retrovirus conference earlier this year.

In a late-breaker session at the recent 11th European AIDS Conference (EACS) in Madrid, Spain (October 24-27, 2007), researchers presented further 52-week data from this trial.

The study included 410 HIV positive participants (85% men) on HAART with documented abdominal fat accumulation. Initially, 273 subjects were randomly assigned to receive once-daily 2 mg TH9507 injections, while 137 received placebo. After 26 weeks, the 315 participants who remained in the study either stayed on tesamorelin or crossed over to the other arm.

Results

• After 26 weeks, patients taking tesamorelin experienced an 18% reduction in visceral abdominal fat from baseline, while those in the placebo group experienced a slight increase.

• After 52 weeks, those who received tesamorelin the whole time maintained the same 18% fat reduction.

• Those who originally received placebo and switched to tesamorelin at 26 weeks experienced a 13% reduction in visceral fat.

• Patients who switched from tesamorelin to placebo, however, soon regained the lost fat, ending with less than a 2% reduction from baseline.

• 36% of patients in the continued tesamorelin group experienced adverse side effects, compared with about half as many in the 2 crossover arms.

• 12% in the continued tesamorelin arm discontinued due to adverse events, again about twice as many as in the crossover arms.

• 14% of patients in the continued tesamorelin arm experienced arthralgia (joint pains) -- mostly during the first 6 months -- compared with 4% in the crossover arms.

These results suggest that in order to attain sustained benefits, patients may have to keep taking tesamorelin over the long-term -- as they must with lipid-lowering statin drugs.

Below is an edited excerpt of a press release from Theratechnologies announcing the study findings and a new educational program:

Theratechnologies Launches Awareness Program in HIV-Associated Lipodystrophy at the European AIDS Conference

Additional data from its Phase 3 clinical trial at 52 weeks also discussed

Montreal, Canada - October 26, 2007 - Theratechnologies (TSX:TH) today presented its first scientific symposium in HIV-associated lipodystrophy to increase the awareness of this disease at the 11th European AIDS Conference (EACS) in Madrid, Spain. Theratechnologies also presented additional positive 52-week safety data from its tesamorelin (TH9507) Phase 3 clinical trial at EACS.

The new data, presented in a late-breaker session, are in line with the safety profile of tesamorelin observed during the initial 26 weeks of treatment. verall, tesamorelin was well tolerated by patients and signals no concerns with respect to glucose intolerance after one year of treatment.

"It is our role as a leader in HIV-associated lipodystrophy to provide the necessary information to clarify the misconceptions about this condition," said Mr. Yves Rosconi, President and Chief executive Officer of Theratechnologies. "Education about this disease is critical. Lipohypertrophy and lipoatrophy are used interchangeably to describe lipodystrophy and this is inaccurate. In addition, the metabolic component of this condition is becoming more known as previously lipodystrophy was considered as mainly a cosmetic change. This scientific symposium at the EACS is our first step to raise awareness about lipohypertrophy and, in 2008, we will begin similar efforts in North America," Mr. Rosconi noted.

Theratechnologies' Scientific Symposium: "Body Fat Changes and Metabolic Abnormalities in HIV: Facing the Challenge"

The Company-sponsored symposium featured four presentations from key opinion leaders in the field of HIV-lipodystrophy aimed at enhancing the understanding of the syndrome and various factors associated with it. The session was moderated by Drs. Peter Reiss, M.D., Ph.D., Associate Professor, Academic Medical Center, University of Amsterdam, Deputy Director, Dutch National AIDS Therapy Evaluation Center, Scientific Advisor, International Antiviral Therapy Evaluation Center, and François Raffi, Head, Infectious Diseases Unit, Hôtel-Dieu University Hospital, Professor, Infectious Diseases, Nantes Medical University.

The symposium's scientific program included the following presentations:

• "Body Fat Changes and Metabolic Complications Associated with Antiretroviral Therapy," by Dr. Pere Domingo, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

• "Increased Cardiovascular Risk in HIV: Contribution of the Different Risk Factors," by Dr. Jens D. Lundgren, Professor, University of Copenhagen, and Chief Physician and Head, Copenhagen HIV Program Hvidovre University Hospital, Denmark.

• "Clinical Management of Metabolic Complications," by Dr. Stefan Mauss, Co-founder, Center for HIV and Hepatogastroenterology, Düsseldorf, Germany.

• "Treatment Options and Strategies for Reducing Lipohypertrophy in HIV," by Dr. Steven Grinspoon, Associate Professor of Medicine, Harvard Medical School, Director of the Massachusetts General Hospital Program in Nutritional Metabolism, and lead investigator for the tesamorelin trial in the United States.

The key messages from the symposium are reviewed below. HIV-associated lipodystrophy is a serious condition associated with metabolic abnormalities that is caused by several factors including the antiviral regimen and the virus itself. Knowledge regarding the definition of lipodystrophy, and lipohypertrophy in particular continues to evolve within the scientific and medical communities.

Lipoatrophy (fat loss in face, limbs, and buttocks) and lipohypertrophy (abdominal visceral fat accumulation) are two separate conditions of lipodystrophy and this distinction is not widely known. What is becoming evident is that the mechanisms that cause lipoatrophy are different than those which cause lipohypertrophy, and therefore it is reasonable to believe that long-term consequences and treatment strategies are likely to differ as well. Specifically, lipohypertrophy may have a negative impact on glucose tolerance and lipid metabolism which could lead to cardiovascular complications for these patients. Furthermore, due to the stigmatizing morphological changes associated with lipodystrophy, patient compliance is reduced, which may impact the efficacy of their antiviral regimen to control HIV.

"The data presented by Dr. Steve Grinspoon indicate that tesamorelin significantly reduces abdominal fat accumulation, while having no significant impact on glycemic control, which is an important consideration for the treated HIV patient population," commented Chantal Desrochers, Vice President, Business Development and Commercialization at Theratechnologies. "With the product profile of tesamorelin known today, I am encouraged that we are in a good position to fill the unmet medical need described by the international HIV leaders at our symposium," Ms. Desrochers concluded.

Additional 52-Week Phase 3 Safety Data Discussed at Late-Breaker Presentation

The late-breaker presentation, entitled "Long-Term Safety and Efficacy of Tesamorelin, a Growth Hormone-Releasing Factor Analogue, in HIV-Infected Patients with Abdominal Fat Accumulation," was made by Dr. Steven Grinspoon.

Safety Results

The primary objective for the study was to evaluate the safety profile of tesamorelin over a 52-week period. Tesamorelin was generally well tolerated by patients in the first 26 weeks of treatment, as presented in February 2007 at the Conference on Retroviruses and Opportunistic Infections (CROI). The safety profile observed during the 26 to 52 week treatment period is in line with the previously reported 26-week data, but with a lower incidence of adverse events. Consequently, only 3% of patients dropped out because of adverse events during the 26 to 52 week treatment period compared with 12% in the first 26 weeks.

In the second treatment period, the four most commonly reported adverse events were: upper respiratory tract infections (6.5%), nasopharyngitis (5.8%), sinusitis (5.2%), and arthralgia (3.9%). In the first 26 weeks the four most commonly reported adverse events were headache (16%), arthralgia (13%), injection site bruising (9%), and diarrhea, peripheral edema, and myalgia (all reported at 8%). In addition, as was the case in the first 26 weeks, no issues related to glycemic control were observed after 52 weeks of treatment.

Hypersensitivity reactions, which are defined as skin reactions extending beyond the injection site, were experienced by 3% of treated patients for the first 26 weeks and only an additional 1% of treated patients at 52 weeks experienced such a reaction. Fifty percent of patients developed antibodies to tesamorelin at 26 weeks, which remained unchanged at 52 weeks. Moreover, the presence of antibodies had no significant impact on VAT loss and IGF-1 levels.

As a summary, the safety profile of tesamorelin at 52 weeks is very satisfactory. The incidence rates for all types of adverse events were less than 10% in the 26 to 52 week treatment period and no new types of adverse events appeared. Overall, the safety profile associated with longer-term exposure is comparable to what was shown at 26 weeks.

Efficacy Results

Patients treated over 52 weeks had lost 18% of their visceral adipose tissue (VAT) at the end of the study with most VAT loss occurring within the first 26 weeks of treatment. Those patients treated with tesamorelin for the first 26 weeks and subsequently placed on placebo experienced a VAT loss of 18% at 26 weeks while completing the 52-week period with a loss of only 2%. This suggests that continuous exposure to tesamorelin is required to maintain VAT loss. There were no clinically significant differences between men and women in terms of VAT loss. Additional efficacy data will be presented, as they become available, at appropriate venues in the future.

About Theratechnologies

Theratechnologies is a Canadian biopharmaceutical company that discovers innovative drug candidates in order to develop them and bring them to market. The company targets unmet medical needs in financially attractive specialty markets. Its most advanced program is tesamorelin, which has recently completed patient randomization for its confirmatory Phase 3 clinical trial for a serious metabolic disorder known as HIV-associated lipodystrophy. Tesamorelin could be the first compound on the market to treat HIV-associated lipodystrophy. The company also has other projects at earlier stages of development.

11/09/07

Sources

J Falutz, S Grinspoon, and others. Long-term safety and efficacy of tesamorelin (TH9507), a growth hormone releasing factor analogue, in HIV-infected patients with abdominal fat accumulation. 11th European AIDS Conference (EACS). Madrid, Spain. October 24-27, 2007. Abstract LBPS 7/3.

Theratechnologies Launches Awareness Program in HIV-Associated Lipodystrophy at the European AIDS Conference. Press Release. October 26, 2007.