The investigational CBL-514 injection, in a small MRI subgroup of a Phase 2b trial, demonstrated an average reduction in visceral fat volume of 12.01% four weeks after completion of the treatment course. The new analysis was reported on 2 October by the EASD and the developer, Caliway; the drug is already being studied in a Phase 3 trial, but it has not been approved and is not a proven treatment for obesity.
Briefly about the main points
- 12,01% — change in visceral fat volume as measured by MRI, rather than total abdominal fat.
- The figure was obtained four weeks after the end of treatment in a small subgroup.
- CBL-514 is being investigated as a local injection, rather than as an appetite suppressant.
- Phase 3 assesses the reduction in subcutaneous abdominal fat and does not imply future approval.
What exactly was measured in the new analysis?
According to the EASD and Caliway, the MRI subgroup analysis of two Phase 2b trials included 23 participants who received CBL-514, and 17 participants in the placebo group for whom follow-up data were available. Four weeks after the end of the treatment course, the mean visceral fat volume in the CBL-514 group was 12.01% lower than the baseline level, whilst in the placebo group it had increased by 5.68%.
The figure 12,01% does not reflect an overall reduction in abdominal fat and is not the result observed four weeks after the first injection. It specifically refers to visceral fat — the tissue surrounding the internal organs, which was measured using MRI after the treatment was completed. Subcutaneous fat is located directly beneath the skin, so these two measures should not be equated.
How does CBL-514 differ from GLP-1 medicines?
According to the developer and the authors of the Phase 2b study, CBL-514 is administered subcutaneously into the lower abdomen and is being developed to reduce localised fat at the injection site. Participants received injections every three weeks over a period of up to 12 weeks.
In the peer-reviewed publication, the compound is described as inducing apoptosis in adipocytes — the programmed death of fat cells. However, the details of the proposed molecular mechanism are partly based on confidential, unpublished material from Caliway; therefore, they cannot be regarded as having been definitively and independently confirmed.
Unlike drugs in the class of GLP-1, which are used to systematically influence appetite and body weight, CBL-514 is being investigated as a local injection for abdominal fat. The available results do not demonstrate the effectiveness of this agent for the treatment of obesity or general weight loss.
What will be assessed in Phase 3
The SUPREME-01 trial is currently recruiting participants. This is a randomised, double-blind, placebo-controlled Phase 3 trial involving approximately 320 adults, which is evaluating the efficacy and safety of CBL-514 in reducing abdominal subcutaneous fat. The protocol involves up to four treatment sessions at four-week intervals.
In the Phase 2b trial, researchers reported mainly mild or moderate temporary reactions at the injection site. However, participants were only monitored for up to 12 weeks after the final treatment session, so the long-term safety and clinical benefits for the treatment of obesity have not yet been established.
The hypothesis that weight may be regained after discontinuing GLP-1 therapy has not been proven in humans either: in the EASD report, such data related solely to animal models. The company expects the first results from the first Phase 3 trial by the end of 2027.
