Tesamorelin for NAFLD in people living with HIV
13 December 2019. Related: Lipodystrophy and metabolic complications, Hepatitis coinfection.
Simon Collins, HIV i-Base
A potential new use for tesamorelin as a treatment for Non Alcoholic Fatty Liver Disease (NAFLD) in HIV positive people was reported based on results from a US study recently published in Lancet HIV. [1]
Tesamorelin is currently licensed in the US as a treatment to reduce visceral fat in people with central fat accumulation (lipodystrophy).
This was a randomised, double-blind, placebo controlled study in 61 HIV positive participants with a hepatic fat fraction (HFF) greater >5%. Participants were randomised to receive tesamorelin (2 mg sub-cutaneous injection once-daily) or matched placebo for 12 months.
Baseline characteristics included mean age 53 (+/– 8) years, 80% male, 30% black race, 16 years HIV infection. Alcohol use was low (<1 drink a week), 13% with diabetes, 45% currently on a lipid-lowering drug. Histological NASH was present in about one-third, with approximately 52%, having no fibrosis and 10-20% having fibrosis stage 1, 2 or 3,
Based on the primary endpoints of change in HFF, tesamorelin significantly reduced HFF compared with placebo (effect size –4·1%, 95% CI –7·6 to –0·7, p=0·018), with no differences after adjusting for baseline measures of race, antiretroviral use, statin use, or smoking.
This was a –37% (95% CI –67 to –7) relative change in HFF, with 35% of participants in the active group having a reduction that brought HFF to <5% compared to 4% on the placebo arm (p=0.0069),
Tesamorelin also prevented progression of fibrosis, with 2 vs 9 participants progressing in the active vs placebo groups respectively (p=0.044).
Tesamoreliin did not affect overall ALT, lipids, or fasting glucose, although ALT was significantly reduced in people with elevated levels at baseline. CRP was also significantly reduced (effect size –4·7 mg/L; 95% CI: –9·2 to –0·2) but with no effect on adiponectin.
The study also included an additional six month open label continuation phase where tesamorelin was provided for all participants.
An accompanying editorial commentary in the same journal notes the importance of these results, given the lack of current treatment, but raises similar concerns to the indication for reducing visceral fat: what happens when tesamorelin is stopped? It also notes that the impact on fibrosis relies on early diagnosis.
COMMENT
Even though NAFLD is common (>30% in the general population), there are no currently approved treatments for NAFLD, in HIV positive people or otherwise. Management involved lifestyle changes that generally need 5-10% weight loss for a significant effect.
Pipeline compounds include elafibranor, obeticholic acid, selonsertib, simtuzumab and cenicriviroc and other studies in HIV positive people include using aramchol, maraviroc, metformin and raltegravir.
These results are therefore intriguing although both the need for daily injections (and the high US price) currently are likely to limit access. A newer formulation was recently developed that requires a smaller injection volume and storage at room temperature. [3]
i-Base has produced a leaflet on NAFLD for use in clinics. [4]
Reference
- Stanley TL et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV 2019. 11 October 2019.
https://doi.org/10.1016/ S2352-3018(19)30338-8 - Lewin S. Tesamorelin, liver fat, and NAFLD in the setting of HIV. Editorial comment. Lancet HIV. 11 October 2019.
https://doi.org/10.1016/ S2352-3018(19)30331-5 - Theratechnologies press release. Theratechnologies starts commercialization of new EGRIFTA SV in the United States. (25 November 2019).
https://www.theratech.com/en/theratechnologies-starts-commercialization-of-new-egrifta-sv-in-the-united-states - HIV i-Base. HIV and fatty liver disease. (June 2019).
https://i-base.info/guides/side/hiv-and-fatty-liver-disease