Fran LowryMay 28, 2010 — The US Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee has unanimously endorsed approval of tesamorelin acetate (Egrifta; Theratechnologies, Inc, Montreal) to induce and maintain a reduction of excess visceral abdominal fat in HIV-infected patients with lipodystrophy.
The committee based its approval on data presented by the sponsor that showed that 57% of patients taking tesamorelin experienced an 8% or greater reduction in abdominal fat compared with 29% of patients taking placebo.
The panel was also positively swayed by "compelling" testimony by 2 HIV-positive patients who told them how devastating it was to live with the unsightly accumulation of belly fat — an adverse effect of antiretroviral therapy — that immediately labeled them as "AIDS patients."
One by one, the 16 members of the panel gave their reasons for their yes votes. All said the sponsor clearly proved what they had set out to prove.
"I voted yes and it was an easy decision. The sponsor was asked to show a reduction of visceral adipose tissue and they did that," said Abraham Thomas, MD, MPH, division head of endocrinology, diabetes, bone and mineral disorders, Henry Ford Hospital, Detroit, Michigan. "They showed an improvement in patients' perception of their body image, that patients felt better about their appearance. That's what they were asked to do and they did that very well in their series of clinical trials."
Clifford J. Rosen, MD, director of clinical and translational research and senior scientist at the Maine Medical Center Research Institute in Scarborough, also found that the decision to endorse tesamorelin was an easy one to make. He added that, in the short term at least, "there are few safety issues, so I didn't feel uncomfortable. This was not a hard choice."
Safety Concerns: IGF-1, Diabetes Risk
But the panel did have safety concerns. Among them were concerns about increases in insulin-like growth factor 1 (IGF-1), which may promote tumor growth.
"I am very concerned about IGF-1," Dr. Rosen said. "There must be some way of labeling about frequent monitoring of IGF-1 levels. I think this is going to be a long-term issue. Currently, it's hypothetical, but it is a concern and both the patient and the prescribing physician should be aware of this."
Earlier in the day, some panel members had also expressed concerns about the increased risk for diabetes with tesamorelin. However, by the time it came to a vote, the panel felt that the benefits of the drug outweighed the risk.
"I harped a lot about diabetes and the risk factors, but I don't think we should be restricting people with HIV who have diabetes," Dr. Thomas said. "If someone has diabetes and is well controlled, that person should have an opportunity because they are suffering the same psychological issues of body image and being identified in the community as being on HIV treatment."
A similar opinion was expressed by David S. Schade, MD, professor of medicine and chief, Division of Endocrinology, University of New Mexico School of Medicine, Albuquerque.
"If this drug does not cause deterioration of glucose control, then it ought to be used in patients with diabetes. We should not exclude them," Dr. Schade said. "I would recommend that the FDA not include any language about excluding patients with diabetes. They can certainly say that there is no data supporting the use of this in diabetes, but I would hate to see all my diabetic patients potentially being excluded from this medication."
Prescribing Guidelines Requested
Panel members also asked the FDA to come up with guidelines for clinicians in prescribing tesamorelin.
"As a clinician, I would like some specific criteria on when to stop Egrifta if the patient is not responding," said Princy N. Kumar, MD, professor of medicine and microbiology, Georgetown University School of Medicine, Washington, DC. "At what point, and with what measurements, do we say to a patient, 'you are not responding, we have given it to you for so many months and you are not going to respond any further'? I would like very concrete information on when to stop."
George A. Bishopric, MD, from Fort Lauderdale, Florida, who was the patient representative on the panel, commented that the degree of suffering that HIV patients with lipodystrophy experience, as well as the fact that there is no other agent for this indication, warranted approval. "We all want follow-up for cardiovascular issues, IGF-1, diabetes, and this will have to be done in postmarketing studies, but I am very happy that it passed."
"There is no question that lipodystrophy causes a fair amount of psychological distress, as well as difficulty in functioning. It has been associated with depression, and depression has been incontrovertibly associated with poor adherence and poor outcomes in disease progression," said Vicki Cargill, MD, director of minority research, Office of AIDS Research, National Institutes of Health, Bethesda, Maryland.
Dr. Cargill added that a registry or another form of postmarketing surveillance is needed, and other panel members agreed.
"The population in this study were mostly Caucasian and do not reflect the population that is heavily impacted by the epidemic, so it would be important to see data in such a population," she said.
The panel also debated whether reducing abdominal fat translated into a reduction in cardiovascular disease risk.
"The issue with regard to cardiovascular outcomes is certainly not shown at all by the sponsor, and we have no clue whether there is an adverse cardiovascular outcome or a benefit by reducing belly fat," said Mark E. Molitch, MD, professor of medicine at the Feinberg School of Medicine, Northwestern University, Chicago, Illinois. "This deserves study, whether through some registry or prospective placebo-controlled trials, which I prefer, but which might be difficult to do."
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