HIV-positive patients with lipodystrophy can be treated safely and effectively with tesamorelin (TH9507) for at least 52 weeks, according to new data presented this week at the 11th European AIDS Conference in Madrid. The results presented at EACS reflect the second half of a one-year study in which patients stopped, started, or remained on tesamorelin therapy to evaluate the long-term effects of the drug.
Preliminary results from the first 26 weeks of the study were reported at the 14th Conference on Retroviruses and Opportunistic Infections (CROI) by Steven Grinspoon, MD, of Harvard Medical School and his colleagues. The second 26 weeks of the study were also reported by Dr. Grinspoon at EACS.
To date, no treatments have been approved for the management of visceral adipose tissue (VAT) increases – a buildup of fat around the gut, deep within the body – seen in many HIV-positive people. However, studies have shown that administration of Serostim (recombinant human growth hormone) reduces VAT – an average 20% drop in VAT after 12 weeks was seen in one recent study – and may also have a therapeutic effect on lipid levels.
Unfortunately, Serostim therapy is associated with some notable side effects, including fluid retention and an increased risk of blood glucose elevations. In fact, Serostim has been turned down for approval by the U.S. Food and Drug Administration for the treatment of lipodystrophy (an appeal is pending).
Theratechnologies, a company based in Montreal, has been experimenting with the use of a synthetic growth hormone release factor (GRF) dubbed tesamorelin. It acts on pituitary cells in the brain, triggering growth hormone production and secretion. This more natural release of growth hormone by the pituitary gland, researchers associated with the development of tesamorelin suggest, may result in treatment benefits similar to those seen in Serostim lipodystrophy studies, but with fewer side effects.
The data reported by Dr. Grinspoon at EACS come from one of two Phase III clinical trials being conducted by the company. The study originally enrolled 412 U.S. and Canadian HIV-positive patients with evidence of lipodystrophy-associated VAT increases.
For the first 26 weeks, patients were randomized to receive either daily subcutaneous injections of 2 mg tesamorelin (273 patients) or placebo (137 patients). Upon completing 26 weeks, patients receiving tesamorelin were re-randomized to switch to placebo (50 patients) or continue taking the drug (154 patients). All patients originally randomized to receive placebo were given tesamorelin for the second 26 weeks of the study.
During the first 26 weeks of the study, according to Dr. Ginspoon’s report at the 14th CROI, patients treated with tesamorelin saw their VAT decrease by 15 percent, compared with pre-treatment measurements. In the placebo group, there was an average 5 percent increase in VAT after 26 weeks. This 20 percent difference between the two groups was statistically significant, meaning that it wasn’t due to chance.
In the second half of the study, patients treated with tesamorelin for a total of 52 weeks had lost 18 percent of their VAT. Dr. Grinspoon noted that most of the fat loss occurred during the first 26 weeks of treatment.
Patients treated with tesamorelin and subsequently given placebo experienced a VAT loss of 18 percent by week 26. Upon switching, VAT concentration were only 2 percent below pre-study levels.
Among patients who switched from placebo to tesamorelin, the 5 percent gain in VAT seen after the first 26 weeks in the study became a 12.5 percent decrease—compared with pre-study levels—during weeks 26 to 52.
Approximately 50 percent of patients treated with tesamorelin developed antibodies to the drug during the trial. However, this did not appear to affect patients’ responses to treatment.
As for safety, Dr. Ginspoon reported at CROI that tesamorelin was generally well-tolerated by patients during the first 26 weeks of treatment. 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 side effects.
Only 3 percent patients dropped out because of adverse events during the second half of the study, compared with 12 percent in the first 26 weeks. From weeks 26 to 52, the four most commonly reported side effects were: upper respiratory tract infections (6.5 percent), colds (5.8 percent), stuffed sinuses (5.2 percent) and joint pain (3.9 percent). During the first 26 weeks of the study, the four most common side effects were headache (16 percent), joint pain (13 percent), injection site bruising (9 percent) and diarrhea, fluid retention and muscle pain (all reported at 8 percent).
Dr. Grinspoon also noted that, as was the case during the first 26 weeks of the study, no issues related to glucose control were observed after 52 weeks of treatment.
In conclusion, Dr. Grinspoon said that the safety profile of tesamorelin at 52 weeks is very satisfactory. As for the rebounds in VAT seen in patients who switched from tesamorelin to placebo, he indicated that continuous treatment with the drug will likely be required to maintain fat loss.