LONDON – Weight loss, lipid reductions, and “robust improvements” in lipid species associated with nonalcoholic fatty liver disease were achieved in patients who were treated with pemvidutide in a first-in-human, phase 1 clinical trial reported at the annual International Liver Congress, sponsored by the European Association for the Study of the Liver.
The presenting study investigator, Stephen A. Harrison, MD, said that pemvidutide, which is also being developed for the treatment of obesity, appeared to be well tolerated. There were no serious or severe adverse events, and no patient had to discontinue treatment because of side effects.
Overall, “pemvidutide represents a promising new agent,” said Dr. Harrison, medical director of Pinnacle Research in San Antonio, Texas.
Dual incretin effect
Pemvidutide is a “balanced” dual agonist of glucagon-like peptide 1 (GLP-1) and glucagon, Dr. Harrison explained in his oral abstract.
“With glucagon, we are working to drive energy expenditure up, and with GLP-1, we’re decreasing food intake,” Dr. Harrison said.
What might set pemvidutide apart from other incretins lies within its structure, Dr. Harrison suggested. The structure has two main regions – one with greater GLP-1 specificity and the other with greater glucagon specificity, and these two areas are linked by a propriety technology called a EuPort™ domain. This is an area which allows the drug to bind to albumin, which increases its serum half-life and enables weekly dosing while slowing its entry into the bloodstream.
“Ultimately, we think that this has impacts, hypothetically, on tolerability and potentially mitigating the need for dose escalation,” said Dr. Harrison.
Weight loss results
The phase 1 study Dr. Harrison presented had a randomized, double-blind, placebo-controlled design with single and multiple ascending doses (SAD/MAD) of pemvidutide being tested. He presented data on the MAD phase only, noting that the SAD phase had been used to determine what doses to use in the latter.
Seventy individuals with a body mass index of between 25 and 40 kg/m2 were recruited and 34 of these were enrolled in the MAD phase of the study. Three doses of pemvidutide were used, given subcutaneously once a week for 12 weeks: Seven participants received 1.2 mg, 9 were given 1.8 mg, 11 had 2.4 mg, and 7 subjects were treated with placebo. Dr. Harrison noted that there were no caloric restrictions in the trial and no lifestyle modifications or interventions.
The average age of study participants ranged from 27 to 35 years and the mean BMI was 30-31 kg/m2 across each group, with their lipid parameters in the upper range of normal.
Clear weight loss reductions were seen across all the pemvidutide groups versus placebo, with the greatest percentage changes in weight loss seen with the two higher doses used. At week 12, there was a 4.9%, 10.3% and 9.0% weight loss in the 1.2-mg, 1.8-mg and 2.4-mg pemvidutide groups compared to 1.6% in placebo-treated individuals.
All patients in the 1.8-mg group achieved a 5% or greater weight loss, Dr. Harrison observed, but there “was a plateauing” effect with the 2.4-mg dose with 89% of patients achieving this target. In comparison, a third of patients on the lowest dose and 20% of those on placebo achieved this target.
The trajectory of weight loss seen in the trial suggests that “the rate of weight loss would continue beyond 12 weeks if we were to continue the therapy” Dr. Harrison said.