Tesamorelin Resolves NAFLD in Some HIV Patients

By Anne Harding

November 15, 2019

NEW YORK (Reuters Health) - Tesamorelin can reduce liver fat and prevent fibrosis progression in HIV patients with non-alcoholic fatty liver disease (NAFLD), according to a new phase-2 trial.

"This study is the first to show a successful therapeutic strategy to reduce liver fat and prevent fibrosis in people with HIV," Dr. Steven K. Grinspoon of Massachusetts General Hospital and Harvard Medical School in Boston told Reuters Health by phone. "In fact, 35% of patients getting the drug versus 4% of placebo patients had their liver fat go back below 5%, in other words resolving NAFLD."

The U.S. Food and Drug Administration approved tesamorelin, which stimulates pulsatile growth-hormone production, in 2010 for reducing visceral fat in patients with HIV and central adiposity.

Dr. Grinspoon and his team hypothesized that the drug might also be helpful for NAFLD, which occurs frequently in people with HIV and is associated with cardiovascular disease and progression to liver fibrosis and cirrhosis.

The researchers randomly assigned 60 HIV patients with a hepatic fat fraction (HFF) of at least 5% based on proton magnetic resonance spectroscopy to 2 mg of tesamorelin once daily or a placebo injection for 12 months. A six-month open-label phase followed in which all patients were given active treatment.

Patients had a mean HFF of 13.8%, and 33% had non-alcoholic steatohepatitis (NASH), the researchers report in The Lancet HIV, online October 11.

Tesamorelin reduced HFF with an effect size of -4.1% (P=0.018) compared with placebo, a -37% relative change over one year.

Two patients on tesamorelin (10.5%) had progression of fatty liver disease compared to 37.5% of the placebo group (P=0.044). However, the drug did not reduce fibrosis in patients with existing fibrotic disease.

C-reactive protein was reduced in the tesamorelin group (effect size -4.7 mg/L). Patients with elevated alanine aminotransferase (ALT) levels at baseline had significantly reduced ALT levels at one year with tesamorelin. The drug had no effect on blood lipids or glucose metabolism.

"Collectively, these data suggest a significant benefit of tesamorelin among people with HIV and NAFLD," Dr. Grinspoon and his team write.

"The treatment is generally well tolerated, and future studies are needed to further define the clinical role of tesamorelin with respect to NAFLD in people with HIV, and potentially other populations," they conclude.

"Increased investment will be needed to increase the awareness of the condition to allow for early diagnosis and a focus on prevention," Dr. Jennifer Audsley of The University of Melbourne and Royal Melbourne Hospital, in Australia, and colleagues note in an editorial accompanying the study. "Tesamorelin provides a new therapeutic approach that is important to managing people living with HIV and NAFLD and warrants further investigation."

The study had no commercial funding. Dr. Grinspoon is the named inventor on a patent application on the effects of tesamorelin for treating liver disease.

SOURCE: https://bit.ly/2qTwJhs and https://bit.ly/3749yBU

Lancet HIV 2019.