Drug Watch: Tesamorelin Update
On May 27, 2010, the FDA advisory committee charged with reviewing the data on tesamorelin unanimously recommended that the agency approve the treatment for marketing. Nearly six months later, the FDA approved tesamorelin "for the treatment of excess abdominal fat in HIV-infected patients with lipodystrophy," as stated in Theratechnologies' November 11 press release. The drug will be marketed in the United States under the brand name Egrifta by EMD Serono, Inc., an affiliate of the major pharmaceutical company Merck.
While the approval of tesamorelin is a welcome development, some concerns remain about the drug's safety and long-term effects. At the May 27 advisory committee meeting, Graziella Soulban, M.D., director of clinical research at Theratechnologies, reported that the tesamorelin-receiving study groups experienced higher rates of pre-diabetes and diabetes than did those taking placebo during the first 26 weeks, although those rates declined by week 52. Study participants who entered the trial with pre-diabetes also ran the risk of developing diabetes during the studies, suggesting that tesamorelin may not be appropriate for people with this (unfortunately common) condition.
A possible safety concern with tesamorelin and other growth hormone products used in the setting of HIV care is that elevated IGF-1 may promote the formation of tumors. Increased IGF-1 levels are an indicator that tesamorelin is working, but this effect must be balanced against the already higher risk of cancers in HIV positive people (see "A Glass Half Full: Cancer Risk for People Living with HIV," in this issue). According to Soulban, however, increased IGF-1 levels were not associated with higher risk of cancer in the Phase III trials.
Further studies are also warranted to more closely examine tesamorelin's safety and efficacy in women. Although men made up the majority of participants in the tesamorelin trials, women are extremely likely to use the treatment if it is approved. In fact, as reported by Massimo Galli, M.D., of the Institute of Infectious and Tropical Diseases at the University of Milan and colleagues, HIV positive women are more likely than HIV positive men to have fat accumulation, including excess VAT. This makes it important to better understand whether the drug affects women's bodies differently. In addition, tesamorelin is contraindicated for use by pregnant or breastfeeding mothers, as changes in growth hormone secretion may be harmful to the developing fetus or infant.
Other lingering -- and important -- questions concern the need for long-term treatment. Tesamorelin's VAT-reducing effect apparently ends once treatment is stopped; as Falutz noted in a 2010 article, "the initial improvements over six months in VAT were rapidly lost in those switching from tesamorelin to placebo." Will life-long treatment therefore be necessary -- and will it be safe and affordable? And will the fact that tesamorelin must be injected deter people from using it long-term?
For one trial participant, at least, injecting the drug daily was not a challenge: "Adhering to this medication regimen was easy," said Lisa Hamilton during the open public hearing at the FDA advisory committee meeting. "Given the opportunity, I would stay on tesamorelin for life." The treatment "improved my quality of life so much, and the physical and psychological burdens [of lipohypertrophy] were lifted."
HIV treatment advocates asked the FDA to approve tesamorelin, but with some important conditions. "We strongly urge against reviewing, approving, or labeling Egrifta as a cosmetic treatment," said long-time treatment advocate Jeff Berry in an eloquent appeal at the advisory panel meeting. Berry likened lipodystophy treatment to reconstructive surgery for women who have had mastectomies: both have benefits that go far beyond the merely "cosmetic."
Hamilton described to the committee how her abdominal fat has returned since the tesamorelin trial ended, making it once again difficult to bend over and perform normal activities of daily life and causing her much anxiety: "Since I've been off the tesamorelin and the abnormal fat accumulations of the abdomen returned, my fears regarding heart attack, hypertension and stroke have returned."
Clearly, treatment for abdominal fat accumulation isn't just about trimming down a protruding belly. Lipodystrophy, said Berry, "is conspicuous and stigmatizing, an overt sign of HIV infection and illness, and according to the collected data and countless anecdotal reports, significantly affects psychological well-being, quality of life, willingness to commence antiretroviral therapy in light of lipodystrophy fears and adherence levels among those on antiretroviral therapy."
No drug or treatment is perfect for everyone, of course, and advocates will need help ensure affordable access. That said, tesamorelin has the potential to improve physical health, antiretroviral treatment adherence and overall well-being for many people living with HIV and its approval is a welcome development in HIV care.
Reilly O'Neal is the editor of BETA.
This article was provided by San Francisco AIDS Foundation. It is a part of the publication Bulletin of Experimental Treatments for AIDS. Visit San Francisco AIDS Foundation's Web site to find out more about their activities, publications and services.
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