Tesamorelin for reduction of central fat accumulation: regulatory decision delayed in the US
Simon Collins, HIV i-Base
In May 2010, the FDA advisory panel reviewing the results of studies of a growth hormone releasing factor (GHRF) called tesamorelin (formerly TH9507, tradename Egrifta) made a universal recommendation 16:0 for approval. It is unusual for the FDA not to follow panel recommendations. However, the formal decision, expected in July was not forthcoming and a press release from Theratechnologies, the company developing tesamorelin, announced that the FDA will not make their decision before October 2010.
Tesamorelin has been shown to reduce central visceral adipose tissue (VAT) in people with HIV-associated lipohypertrophy. However, the effect is largely seen during the first six months treatment and subsequently reaches a lower plateau while maintained on treatment, with VAT returning if tesamorelin is discontinued.
The study design has been criticised for several reasons.
Firstly, the cross-over design means that data for many participancts is limited to 26 weeks. Secondly, all patients were had to discontinue GHRF at week 48 having to experience earlier benefits then reverse. Thirdly, no roll-over expanded access programme was provided by the company, even when the reversal was known due to the cross-over study design.
The limited trial data conclude that lifelong treatment is needed in order to maintain benefit. However, because all participants had treatment withdrawn, there has been no research into a maintenance dose. A roll over programme after 48 weeks would have been the ideal setting to study maintenance doses, essentail for minimising both risk of toxicity and future cost of treatment.
It is unclear whether these longer-term safety questions are related to the delayed FDA decision. Community demand for any effective treatment is clearly strong. The clinical trials showed a slightly increased risk of developing diabetes over the short time for the studies, so the longer-term risk needs to be followed closely in phase 4 studies, should approval eventually be decided. Further maintenance dose studies are also clearly warranted.
Tesamorelin has not been submitted to the EMA for regulatory approval. None of the European particiapant have been offered compassionate access to the compound.
- FDA Advisory Committee Meeting to Review Egrifta. (27 May 2010). http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm205680.htm
- Theratechnologies Press Release: Update on timeline for FDA Action Date for
Theratechnologies tesamorelin New Drug Application Montreal Canada (20 July 2010). http://www.theratech.com/en/news-events/news.php?id=381&year=2010