What if you could inject a drug into a “problem area” – like abdominal fat – that could kill off fat cells and reduce fat stores in that localized spot? That’s what a novel drug from Taiwan’s Caliway Pharmaceuticals offers, the world’s very first injection that triggers programmed fat-cell death in a targeted area, like the belly or the thighs.
Known as CBL-514, this small-molecule drug induces adipocyte apoptosis, which kills fat cells rather than starves them, meaning different regions of subcutaneous fat stores can be rapidly reduced in just a few weeks after a single dose. It’s currently being tested for three uses: Non-surgical fat reduction, Dercum’s disease – which causes painful fatty tumors to build up around the body, and cellulite.
“Administered via subcutaneous injection, CBL-514 has demonstrated a favorable safety and tolerability profile, enabling significant localized fat reduction without surgery and delivering results comparable to liposuction,” Caliway has stated.
While it’s being investigated for various applications, the leading one – and the one expected to be on the market first – is for the non-surgical reduction of problematic abdominal fat.
CBL-514 has completed two successful Phase 2b studies (CBL-0204 and CBL-0205) and is about to undertake two pivotal global Phase 3 clinical trials in the second half of 2025.
In the most recent CBL-0205 Phase 2b trial, 75% saw their abdominal fat reduce by at least one grade on the Abdominal Fat Rating Scale (AFRS) four weeks after the initial single shot. This meant it passed its efficacy endpoint to satisfy the US Food and Drug Administration (FDA), which it had already demonstrated (along with safety and tolerability) in the previous 2b trial.
Right now, the only drug approved for localized fat redution is ATX-101 – or deoxycholic acid injection – which has been effective in reducing adipose stores in small areas but comes with serious side effects including skin necrosis, ulceration, nerve injury and infections. CBL-514 hasn’t caused any of these issues even with multiple doses across much larger areas of the body.
In the last trial, more than 75% of participants reached their target fat volume loss after one or two injections, and the mean fat loss was more than double this. It closely mirrored the results from the initial Phase 2b trial, with results released in December 2024 detailing how 76.7% of its 107 participants who received the treatment improved by at least one grade on the five-grade AFRS. Three quarters of those participants only needed a single shot for this.
“CBL-514, a first-in-class small-molecule drug, is a lipolysis injectable that can induce adipocyte apoptosis and lipolysis to reduce subcutaneous adiposity in treatment areas without causing any systematic side effects on the central nervous system, cardiovascular system, and respiratory system,” the company noted. “Caliway’s preclinical studies have shown that CBL-514 upregulates the apoptosis mediators caspase 3 and Bax/Bcl-2 ratio and then induces adipocyte apoptosis in vivo and in vitro.”
While it has obvious aesthetic application – non-surgical body-sculpting – the first-in-class drug stands to have broader benefits. Abdominal fat, particularly in midlife and later in life, has been implicated in a number of serious conditions including chronic pain, stroke and cardiovascular disease. While CBL-514 doesn’t specifically target the deeper visceral fat in the region, it can reduce subcutaneous fat by more than 25%, which reduces chronic disease risk and positively impacts hard-to-treat visceral fat.
A safe, localized, non-surgical fat-loss treatment has so far eluded scientists.
Back in 2023, the FDA approved CBL-514 as an Investigational New Drug (IND). A year later, it received European Medicines Agency (EMA) approval, being granted Orphan Drug Designation status for the treatment of Dercum’s disease.
In May, the company got the seal of approval to move on to its final clinical trial stage; the first Phase 3 trial will take place in the US and Canada, and a second in the US, Canada and Australia – both are in the recruitment stage now. The first Phase 3 cohort will feature around 300 participants across close to 30 clinical sites in North America.
“We are pleased to have reached alignment with the FDA on both study design and indication,” said Vivian Ling, Chief Executive Officer of Caliway. “The Agency agrees that the ‘reduction of abdominal subcutaneous fat’ as the proposed indication reinforces our confidence in CBL-514’s differentiated value, and its potential to redefine standards in aesthetic medicine.”
If it delivers in these larger trials, it could be on the market within 12 months.
The results of the most recent Phase 2b clinical trial was published in the Aesthetic Surgery Journal.
Source: Caliway Biopharmaceuticals
