Posted on Dec 07, 2020, 7 p.m.
A new study has revealed an antibody mimetic of fibroblast growth factor 21 (FGF21) that is safe and effective in reducing the weight of obese patients in a recent clinical study. Led by Puneet Arora (Principia Biopharma, CA, USA), the team first conducted trials in non-human primates before moving on to a small clinical trial to test their obesity treatment in a human model.
The task of finding new resolutions to the obesity pandemic has been a key focus for researchers in the last decade. The simple in theory, but often more challenging in practice, advice to follow a balanced diet in combination with regular exercise will always be the best advice for long-term weight loss and health. However, the rapid advance of the obesity crisis demands further strategic and therapeutic interventions to be available to properly control the condition on a population scale.
This demand for obesity treatments has been thrown into the limelight due to the head-on collision of the obesity pandemic with COVID-19. People with obesity infected by SARS-CoV-2 are 74% more likely to require intensive care and are 48% more likely to die than those in a healthier weight range .
A pre-existing experimental method for reducing weight includes the application of manipulated FGF21 – a hormone that regulates metabolism, eating behavior and energy expenditure – leading to a beneficial change in metabolic health in humans, non-human primates and rats. Unfortunately, these molecules are quickly broken down in the body and need to be administered so frequently that they are practically unviable as a clinical treatment.
To address this issue, the team developed a more stable molecule – an antibody-based FGFR1/KLB receptor agonist. First, they tested the molecule in nonhuman primates to see if it produced the same effect as FGF21 analogs. Named BFKB8488A, the antibody-drug was shown to reproduce biomarkers and metabolic effects of FGF21.
This was followed by a phase 1 placebo-controlled clinical trial of 60 obese, but otherwise healthy, patients. The treatment group received a single subcutaneous injection and were monitored for the 8–16 weeks post-injection. All participants of the study then received a calorically balanced diet during a one-week confinement period.
The research team found that the treatment group lost an average of 1.20kg during the confinement period compared to the 0.28kg lost in the placebo group. The team also observed, “profound and sustained dose-related reductions in triglycerides and LDL cholesterol, as well as marked increases in HDL cholesterol.”
The treatment group also observed a reduction in calorie intake one week after treatment, reaching the maximum decrease of 50% between days 15–22. This decrease in intake was matched by an acquired aversion to sweet foods.
While the weight loss experienced was typically regained 3 days after patients were removed from their dietary confinements, the study did highlight that weight loss began to occur prior to the onset of changes in dietary behavior. This indicates that the antibody therapeutic is capable of inducing weight loss in a metabolic manner as opposed to simply by repressing appetite.
Further clinical trials are required, but in a time when reducing obesity has never been more important, the team may have uncovered a practical treatment course that could prove pivotal in the battle against obesity.
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