FDA Committee Unanimously Votes to Approve Tesamorelin (Egrifta) for Lipodystrophy

The U.S. Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee recommended by a 16-0 vote last Thursday that the agency should approve tesamorelin (brand name Egifta), a synthetic human growth hormone-releasing factor developed by Theratechnologies, for the treatment of visceral abdominal fat accumulation in people with HIV-related lipodystrophy. The recommendation is based on Phase 3 study results showing that people taking tesamorelin were nearly twice as likely to experience at least an 8% reduction in visceral fat. The main side effect of concern is elevated blood glucose and diabetes.

Previous research showed that recombinant human growth hormone (Serostim) reduced visceral adipose or fat tissue, but it can lead to unacceptable side effects including increased blood glucose, swelling, bone pain, and carpal tunnel syndrome. In contrast, tesamorelin (formerly TH9507) is a growth hormone-releasing factor that works by stimulating the pituitary gland in the brain to secrete more growth hormone.

Investigators hoped tesamorelin might provide benefits similar to direct growth hormone administration but with fewer adverse effects. As recently reported in the March 1, 2010 Journal of Acquired Immune Deficiency Syndromes, patients receiving tesamorelin experienced an average visceral fat reduction of 10.9% at 6 months, compared with just 0.6% among placebo recipients; by 12 months, the reduction in the tesamorelin arm reached 17.5%. These benefits were rapidly lost, however, when patients stopped taking the drug.

Trunk fat, waist circumference, and waist-to-hip ratio all improved significant in the tesamorelin arm and recipients reported improved feelings about body image. Tesamorelin was associated with lower total cholesterol and did not cause significant side effects including blood glucose abnormalities, although levels of insulin-like growth factor-1 (IGF-1) did increase significantly.

Christian Marsolais from Theratechnologies presented data at the May 27 meeting showing that 57.4% of Phase 3 trial participants who received tesamorelin experienced at least an 8% reduction in visceral abdominal fat, compared with 29.3% of those taking placebo. Clinical trial participants also testified about the benefits of the drug.

Members of the committee discussed conflicting reports about tesmorelin's effects on blood glucose. Theratechnologies researchers reported, for example, that elevated blood glucose and diabetes were more common among study participants during the first 6 months on tesamorelin, though rates evened out by 12 months. An FDA safety review revealed that while nearly half of tesamorelin recipients showed no blood glucose elevations, about 17% had 3 or more elevated measurements, with a higher risk among people with pre-existing glucose abnormalities.

Reviewers were also concerned that increased IGF-1 levels might promote tumor development, but cancer rates were not higher among tesamorelin recipients in Phase 3 trials. Although excess fat is a risk factor for cardiovascular disease, differences in cardiovascular event rates have also not been seen in tesamorelin trials to date.

Committee members determined that the benefits of tesamorelin for HIV positive people with lipodystrophy outweigh the risks, but they called for further studies to monitor its safety and efficacy over a longer period.

The full FDA is not required to follow recommendations of its advisory committees, but it usually does so. The agency has indicated that it expects to complete its review and issue an opinion on tesamorelin approval by July 27, 2010.

6/4/10

Sources

Theratechnologies. Theratechnologies announces positive vote by FDA Advisory Committee for tesamorelin. Press release. May 27, 2010.

Food and Drug Administration. Tesamorelin (Egrifta) Briefing Document. May 27, 2010.

L Richwine. US panel backs Theratech drug for HIV patients. Reuters. May 27, 2010.