Details of a new injection that targets fat cells will be released at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2).
Studies show that the new drug, CBL-514, reduces levels of subcutaneous and visceral fat. The data also suggest that it helps attenuate weight regain on stopping GLP-1 receptor agonist drugs (GLP1-RAs), says Dr W. Timothy Garvey, of the University of Alabama at Birmingham, Birmingham, USA.
CBL-514 selectively induces apoptosis (self-destruction) of adipocytes, or fat cells, while leaving other cells untouched.
In phase 2 clinical trials, the drug reduced the volume of subcutaneous adipose tissue – the layer of fat that lies just beneath the skin and can be "pinched" – with 69.6% of treated participants achieving a reduction of at least 150 mL at the 8-week follow-up, compared with 0% of those receiving placebo1.
In preclinical studies2 (animal models), it reduced weight and levels of subcutaneous and visceral abdominal tissue (VAT). Visceral fat is hidden deep within the abdomen, wrapped around the internal organs. It is very metabolically active and a key driver of insulin resistance, type 2 diabetes and cardiometabolic conditions such as heart attacks and strokes.
More weight was lost when the drug was given along with the GLP1-RA tirzepatide. In addition, rats given CBL-514 and tirzepatide regained less weight when tirzepatide was stopped than rats given tirzepatide alone.
The hypothesis is that the reduction in fat cells limits the amount of fat that can be reaccumulated, slowing weight regain.
While GLP1-RAs are highly effective for weight loss, many people regain weight after stopping treatment. The hope is that CBL-514 will help people keep weight off – allowing them to sustain the health benefits of weight loss, such as improvements in blood pressure, blood sugar and cholesterol, says Professor Garvey. However, research is needed to prove this.
For the latest analysis, Prof Garvey and Ms Yu-Fang Ling, of the drug's developer, Caliway Biopharmaceuticals, in New Taipei City, Taiwan used data on a subgroup of participants from the phase 2 trials (CBL-0204 and CBL-0205) to assess CBL-514's effect on visceral fat in human subjects. They focused on trial participants for whom MRI data was available.
The participants (BMI 22-30 kg/m2) received a course of injections, with the exact number depending on the thickness of their abdominal fat, of up to 600mg of CBL-514 (n=23) or placebo (n=17) (age range 36.4 years to 42.4 years) into the lower abdomen every three weeks for up to 12 weeks The number of injections was reduced as the participant's fat thickness decreased and were stopped when the thickness reached a low enough level. MRI scans were used to measure visceral adipose tissue at baseline, four and eight to 12 weeks after the last treatment.
The baseline sex distribution for the VAT subgroup was as follows:
Group |
n |
Female |
Male |
CBL-514 |
23 |
17 (74%) |
6 (26%) |
Placebo |
18 |
10 (56%) |
8 (44.4%) |
(Note: The baseline VAT subgroup included 41 participants (CBL-514, n=23; placebo, n=18). The 40 participants reported in the press release (CBL-514, n=23; placebo, n=17) refer to those with available 8–12-week follow-up data)
VAT volume was similar in the two groups at baseline: 563.85 ml in the CBL-514 group and 659.81 ml in the placebo group. It then decreased in those receiving the drug and increased in those given the placebo.
Four weeks after the last treatment, average VAT volume had decreased by 12.01% from baseline in the CBL-514 group, while it had increased by 5.68% in the placebo group, representing a between-group difference of 17.69%
At the later follow-up – 8 weeks after the last treatment in CBL-0205 and 12 weeks after the last treatment in CBL-0204 – average VAT volume was 10.45% lower than at baseline in the CBL-514 group, while it had increased by 11.76% in the placebo group, representing a between-group difference of 22.21%.
Other than mostly mild-to-moderate and transient injection-site reactions, such as pain, swelling and redness, CBL-514 was generally well tolerated, with no serious adverse events reported.
The researchers conclude that CBL-514 significantly reduced abdominal VAT volume compared with placebo – and that the research as a whole shows that the drug can reduce both visceral and subcutaneous fat.
Professor Garvey says: "We expect that patients will be pleased by the cosmetic effects, such as the flatter stomach that can come with subcutaneous fat loss. But it is the reduction in body weight, loss of visceral fat and the improvements in blood pressure, cholesterol and the like that should be associated with this that will be important for health."
He adds that liposuction and abdominoplasty only address subcutaneous fat and are more invasive.
"This is a highly innovative approach to obesity pharmacotherapy that has produced some remarkable results in early human trials," says Professor Garvey.
Recruitment for the first of two phase 3 trials is under way. These randomised placebo-controlled studies will evaluate the safety and efficacy of CBL-514 for nonsurgical abdominal fat reduction, with the first results expected at the end of next year.
