Efficacy and Safety of CBL-514 Injection in Reducing Abdominal Subcutaneous Fat: A Randomized, Single-Blind, Placebo-Controlled Phase II Study

Abstract

Background

A small-molecule injectable drug, CBL-514, has shown promising efficacy and safety for subcutaneous fat reduction.

Objectives

To further evaluate the efficacy and safety of CBL-514 for abdominal subcutaneous fat reduction.

Methods

In this single-blind, randomized, parallel-group, placebo-controlled Phase 2 trial, 76 participants were randomized (2:1) to receive up to 4 CBL-514 treatments (2 mg/cm², maximum 600 mg/treatment) or placebo, administered subcutaneously to the abdomen every 4 weeks. Two follow-up visits were conducted at 4 and 8 weeks following final treatment. Changes in abdominal subcutaneous fat thickness and volume were measured by ultrasound. The primary endpoint was the proportion of participants with subcutaneous fat volume loss of ≥150 mL from baseline compared with placebo.

Results

In the intention-to-treat population, a significantly higher proportion of CBL-514-treated participants achieved ≥150 mL subcutaneous fat volume reduction from baseline compared with placebo-treated participants at both follow-up visits. At 8 weeks post final treatment, 69.6% of CBL-514-treated participants lost ≥150 mL subcutaneous fat, compared with none in the placebo group (P < .001). Moreover, 60.9% of participants in the CBL-514 group further achieved the ≥200 mL subcutaneous fat loss threshold. Of the 28 participants in CBL-514 group (n = 50) who lost ≥150 mL subcutaneous fat, 42.9% (12/28 participants) achieved this target after a single treatment. The most common treatment-emergent adverse events were injection site reactions and were of mild-to-moderate severity.

Conclusions

CBL-514 treatment significantly reduced abdominal subcutaneous fat volume with a favorable safety profile. As a noninvasive treatment, CBL-514 could be a new, promising alternative therapy for effective targeted subcutaneous fat reduction.

Level of Evidence: 2

Invasive procedures for body sculpting, such as liposuction and abdominoplasty surgeries, provide pronounced results but are associated with the risk of severe side effects, high financial costs, and prolonged recovery time.^1-4 For nonobese individuals and those seeking lower risk, more economical, and localized fat reduction, noninvasive and minimally invasive cosmetic techniques have become popular.⁵ Nonsurgical procedures for localized subcutaneous fat reduction, such as low-level laser therapy, laser lipolysis (using 1060- and 1064-nm lasers), cryolipolysis, radio frequency, and high-intensity focused ultrasound, lead to shorter downtime. However, patient satisfaction levels and the severity of adverse effects vary across modalities, ranging from mild symptoms like transient erythema, pain, and bruising to more severe complications, including dermal injury, subcutaneous nodules, severe frostbite, asymmetry, and postcryolipolysis paradoxical adipose hyperplasia.^5-10 Furthermore, the fat reduction efficacy of each of these noninvasive treatments depends on the consistent and optimal use of the respective high-cost devices.¹¹

There is considerable interest and potential for the use of injection lipolysis for targeted and localized subcutaneous fat reduction. ATX-101 (deoxycholic acid injection), currently the only FDA-approved minimally invasive injectable treatment for fat reduction, has shown efficacy in reducing submental fat,^12-14 with sustained results up to 3 years in most patients,¹⁵ but its associated adverse effects include skin necrosis, ulceration, neuropraxia of the marginal mandibular nerve, and infections.¹⁶ The use of ATX-101 for targeted fat reduction over larger body areas remains under-explored.¹⁷

CBL-514 (Caliway Biopharmaceuticals, New Taipei City, Taiwan) is a small-molecule injection lipolysis agent that promotes adipocyte apoptosis and targeted subcutaneous fat reduction in nonclinical studies without causing any skin necrosis, ulceration, nerve injury, and systemic side effects. (Caliway Biopharmaceuticals, unpublished confidential reports).¹⁸ In a proof-of-concept Phase 2a study (ClinicalTrials.gov: NCT04698642), single doses of CBL-514 showed a favorable and acceptable safety profile as well as efficacy in reducing subcutaneous abdominal fat at multiple dose levels.¹⁷ Here, we report results from a randomized, single-blind, placebo-controlled, parallel-group Phase 2 study to further assess CBL-514 efficacy and safety for abdominal fat reduction (Clinical trial registration no.: NCT04897412; https://clinicaltrials.gov/study/NCT04897412).

METHODS

Trial Design, Participants, and Interventions

This Phase 2, randomized, single-blind, parallel-group, placebo-controlled trial was conducted from February 2022 to March 2023, in 5 centers in the United States and Australia. Eligible participants were males or females aged 18 to 64 years, with a BMI of >18.5 and <35 kg/m² and body weight (BW) ≥50 kg. Participants had to have an abdominal skinfold thickness of 3 to 8 cm measured by calibrated caliper. Other required health criteria included good condition of skin in the treatment area, normal liver, renal, cardiovascular, and immune function, and no known infectious disease or cancer. A full list of inclusion and exclusion criteria is provided in Supplemental Appendix A.

Participants who met the eligibility criteria were randomly assigned in a 2:1 ratio to receive injections of CBL-514 or placebo (Supplemental Figure 1). Randomization was performed using a central randomization system. The trial used a single-blind design, in which participants were blinded to treatment through visual barriers while investigators, site staff, and the sponsor, including the medical monitor, remained unblinded. Participants were required to maintain a stable weight. Any deviation ≥3 kg from baseline resulted in discontinuation. Additionally, failure to comply with treatment and follow-up schedules, such as extending the treatment interval beyond 6 weeks or not completing follow-up visits within the specified time frames, also resulted in withdrawal from the study.

The participants were scheduled to have up to 4 treatments at 4-week intervals, followed by follow-up visits at 4 and 8 weeks following final treatment. A reference point (ie, the most prominent area on the anterior abdomen) was determined to ensure consistency in treatment application. Each participant received a minimum of 25 and a maximum of 50 injections per treatment, at the discretion of investigators, depending on the amount of subcutaneous fat on the abdomen. Each injection, spaced 2.45 cm apart, delivered a volume of 2.4 mL of CBL-514 (2 mg/cm²; up to 600 mg per treatment) or placebo (normal saline in an equivalent volume). The dosing scheme is detailed in Supplemental Table 1. If a participant had insufficient residual fat to warrant subsequent treatments, they proceeded directly to the follow-up visits.

The trial sponsor, Caliway Biopharmaceuticals, was involved in study design; collection, analysis, and interpretation of data; writing the manuscript; and the decision to submit it for publication.

Trial Oversight

The trial was conducted in accordance with the principles of the Declaration of Helsinki, the Good Clinical Practice guidelines of the International Council for Harmonization, and applicable local regulatory requirements. All participants provided written informed consent before participating in the trial. The study protocol was reviewed and approved by the Institutional Review Board, Advarra, Inc., Columbia, MD (application no.: Pro00057157) and the Human Research Ethics Committee, Bellberry Limited, Eastwood, South Australia, Australia (application no.: 2020-08-754-AB-A-9).

Outcomes and Assessments

The primary efficacy outcome was the proportion of participants exhibiting ≥150 mL subcutaneous fat volume loss from baseline to the 4- and 8-week follow-up visits in the CBL-514 and placebo groups. Secondary efficacy endpoints included additional measures of fat reduction: the proportion of participants with a subcutaneous fat volume loss of ≥200 mL, the number of treatments required to achieve ≥150 mL subcutaneous fat volume loss, and the overall reduction in subcutaneous fat volume.

Assessments were conducted at each visit. Subcutaneous fat thickness was measured using ultrasound at 4 scan spots, 4 and 10 cm to the right and left of the reference point. To reduce variability among personnel, only 2 trained sonographers from each imaging center were designated to conduct and collect study measurements. Three ultrasound scans were performed at each point to obtain an average subcutaneous fat thickness value. The subcutaneous fat volume loss was calculated using the cuboid volume formula (volume = basal area × height). The basal area was a defined treatment area of 300 cm², whereas the height represented the average thickness of the subcutaneous fat, determined from ultrasound scans at 4 points.

Multiview photographs were acquired from 8 distinct angles and used to create 3-dimensional (3D) body models using the 3D LifeViz Body system (QuantifiCare, Biot, France).

Safety assessments were treatment-emergent adverse events (TEAEs) and clinical assessments (laboratory tests, vital signs, electrocardiograms [ECGs], physical examinations, and injection site reactions). Injection site reaction AEs were recorded as distinct events for each treatment. Participants recorded any injection site changes or discomfort in a diary.

Statistical Analysis

Approximately 75 participants were planned to be enrolled and randomized (CBL-514: 50 participants; placebo: 25 participants). Because of the exploratory nature of this Phase 2 clinical trial, limited previous data were available to inform sample size calculations, and the sample size was determined with reference to the previous Phase 2a study.

Efficacy analyses were conducted on the intention-to-treat (ITT) population (all assigned/randomized participants) and the per-protocol (PP) population (the subset of the ITT population who had no efficacy-related major protocol violations, completed all study treatments and follow-up procedures, and had stable BW). Safety analyses were conducted on the safety population (all enrolled participants who received at least 1 treatment of the study drug).

Proportions achieving target fat volume loss between the treatment groups were compared using Fisher's exact test. Mixed models for repeated measures were used to compare fat volume change over the study in the treatment groups, with fat volume as the dependent variable, fixed effects of baseline fat volume, treatment group, visit, and an interaction between treatment group and visit variables. All analyses were performed without adjustment for multiple testing. All statistical testing was performed at a 2-sided significance level of 5% unless otherwise specified. Analyses were performed using SAS Version 9.2 (SAS Institute, Cary, NC).

RESULTS

Participants

In total, 130 participants were screened for eligibility, 81 were enrolled, and 76 were randomized (50 in the CBL-514 group and 26 in the placebo group). Of the 81 participants enrolled, 5 participants withdrew before randomization and 1 withdrew after randomization before treatment. Overall, 75 participants were treated: 49 participants received CBL-514, and 26 participants received placebo. Of the 75 participants treated, 38 completed the study and 37 did not. Reasons included loss to follow-up (6/37), participant withdrawal (7/37), weight instability (7/37), inability to comply with the treatment or follow-up visit schedule (6/37), and adverse events (4/37). The ITT population included 76 participants, and the PP population included 30 participants (Figure 1). The CBL-514 and placebo groups were similar in terms of their characteristics. The mean age of participants in the CBL-514 group was 46.3 years (range, 29-63 years), comprising 47 females (94.0%) and 3 males (6.0%). In the placebo group, the mean age was 49.3 years (range, 25-63 years), with 21 females (80.8%) and 5 males (19.2%). Follow-up visits were conducted at 4 and 8 weeks following final treatment. Both groups exhibited minimal BW changes from baseline to the 4-week (Visit 6) and 8-week (Visit 7) follow-up visits; the CBL-514 group showed mean increases of 0.45 and 0.02 kg, whereas the placebo group had mean decreases of 0.76 and 0.26 kg, respectively (Table 1).

Figure 1.

Participant disposition. *ITT population: All assigned or randomized participants, regardless of whether they receive treatment or not. ^†Safety population: All participants enrolled in the study who received at least 1 dose of the study drug. ^‡PP population: All participants in the ITT population who had no efficacy-related major protocol violations, completed all study treatment and follow-up procedures, and had stable BW (see Supplemental Appendix B for inclusion criteria for participants in the PP population). ITT, intention-to-treat; PP, per protocol.

Table 1.

Participant Characteristics (ITT Population)

	CBL-514 600 mg (n = 50)	Placebo (n = 26)
Age at screening, mean ± SD (years)	46.3 ± 9.3	49.3 ± 10.7
Gender
Female, n (%)	47 (94.0)	21 (80.8)
Male, n (%)	3 (6.0)	5 (19.2)
Race, n (%)
Asian	2 (4.0)	3 (11.5)
Black or African American	5 (10.0)	3 (11.5)
White	43 (86.0)	19 (73.1)
Multiple	0	1 (3.8)
BMI at baseline, mean ± SD (kg/m2)	27.77 ± 4.23	26.99 ± 3.54
Body weight at baseline, mean ± SD (kg)	77.22 ± 14.43	77.70 ± 13.38
Body weight change from baseline, mean (kg)
4-week follow-up (Visit 6)	0.45	−0.76
8-week follow-up (Visit 7)	0.02	−0.26
Subcutaneous fat volume at baseline, LS mean ± SE (mL)	974.40 ± 19.69	981.22 ± 27.12
Subcutaneous fat volume at baseline, mean ± SD (mL)	1006.03 ± 329.44	908.39 ± 203.81

ITT, intention-to-treat; LS, least-square; n, number of participants in the ITT population in each treatment group; SD, standard deviation; SE, standard error.

Proportion of Participants Achieving Target Subcutaneous Fat Volume Reduction (≥150 and ≥200 mL) With CBL-514 or Placebo

The study met the primary endpoint and all secondary endpoints. In the ITT population, 63.9% (23/36) of participants in the CBL-514 group showed ≥150 mL subcutaneous fat volume reduction from baseline (95% CI, 46.22%-79.18%), compared with 17.4% (4/23) (95% CI, 4.95%-38.78%) in the placebo group (P < .001) at the 4-week follow-up visit. At the 8-week follow-up, 69.6% (16/23) (95% CI, 47.08%-86.79%) of the CBL-514 group and 0.0% (0/16) (95% CI, not estimable) of the placebo group (P < .001) had achieved ≥150 mL fat volume loss (Figure 2A). This was consistent with the PP analysis (Figure 2B).

Figure 2.

Proportion of participants who lost at least 150 and 200 mL of subcutaneous fat compared with baseline in (A, C) ITT and (B, D) PP population, respectively, from Visit 2 (baseline) to Visits 6 and 7. **P < .01, ***P < .001. ITT, intention-to-treat; PP, per protocol.

Of 28 participants in the CBL-514 group (ITT population) who lost ≥150 mL subcutaneous fat volume, 42.9% (12/28) achieved this fat volume reduction after just 1 treatment, and 35.7% (10/28) required 2 treatments (PP population: 44.4% [8/18] and 27.8% [5/18], respectively; Supplemental Table 2).

A similar trend was observed for fat volume reduction of ≥200 mL. In the ITT population, a significantly higher proportion of CBL-514-treated participants achieved subcutaneous fat volume reductions of ≥200 mL compared with placebo-treated participants at both follow-up visits (CBL-514: 58.3% [21/36], 95% CI, 40.76%-74.49%; placebo: 8.7% [2/23], 95% CI, 1.07%-28.04%; P < .001 at the 4-week follow-up; CBL-514: 60.9% [14/23], 95% CI, 38.54%-80.29%; placebo: 0.0% [0/16], 95% CI, not estimable; P < .001 at the 8-week follow-up; Figure 2C). PP results were consistent with those of the ITT (Figure 2D).

Reduction in Subcutaneous Fat Volume After CBL-514 or Placebo Treatment

In the ITT population, CBL-514-treated participants showed a least-square (LS) mean change in fat volume of −199.80 mL (95% CI, −246.59 to −153.02; P < .001) at the 4-week follow-up and −209.46 mL (95% CI, −252.92 to −166.00; P < .001) at the 8-week follow-up, compared with baseline. These reductions were significantly larger than those in placebo-treated participants, with a between-group difference of −206.62 mL (95% CI, −276.09 to −137.16; P < .001) at the 4-week follow-up and −216.28 mL (95% CI, −288.28 to −144.28; P < .001) at the 8-week follow-up, respectively (Figure 3A).

Figure 3.

Change in subcutaneous fat volume over the treatment area measured by ultrasound from baseline to subsequent visits in (A) ITT and (B) PP population. ^aLS mean change from baseline. ^bLS mean difference from baseline compared with placebo (mean difference [95% CI]). ITT, intention-to-treat; PP, per protocol.

In the PP population, CBL-514-treated participants showed LS mean fat volume changes of −314.70 mL (95% CI, −382.67 to −246.73; P < .001) at the 4-week follow-up and −279.45 mL (95% CI, −335.07 to −223.83; P < .001) at the 8-week follow-up. Fat volume loss was significantly greater with CBL-514 than with placebo, showing a between-group difference of −312.08 mL (95% CI, −434.31 to −189.85; P < .001) at the 4-week follow-up and −276.83 mL (95% CI, −399.87 to −153.79; P < .001) at the 8-week follow-up (Figure 3B).

We additionally assessed the proportion of participants who achieved ≥250 mL subcutaneous fat volume reduction. In the ITT population, 44.4% (16/36; median reduction [interquartile range, IQR] 233.25 [56.63-338.81] mL) and 52.2% (12/23) (median reduction [IQR] 255.00 [106.50-372.75] mL) of the CBL-514 group participants achieved this threshold at the 4- and 8-week follow-up, respectively. No participants in the placebo group reached this threshold (data not shown).

Figures 4 and 5 show representative photographs of the treatment areas from 2 participants with moderate or severe fat levels at baseline, taken before and after CBL-514 treatment (baseline, 4-week follow-up, and 8-week follow-up). In both participants, substantial reductions in fat volume were observed at both follow-up visits (40.85%-47.37%), with minimal changes in BW (<1 kg; Supplemental Table 3). A noticeable reduction in subcutaneous fat in the lower abdomen was clearly visible in the photographs.

Figure 4.

Representative pre- and posttreatment photographs of Participant A, a 49-year-old female with moderate fat accumulation at baseline. The images were taken during baseline (Visit 2: A, D, and G) and follow-up visits (Visit 6: B, E, and H; Visit 7: C, F, and I) and include front, oblique, and lateral views of the abdomen, respectively. These representative images are extracted from the 3D model generated by the QuantifiCare 3D LifeViz Body system.

Figure 5.

Representative pre- and posttreatment photographs of Participant B, a 46-year-old female with severe fat accumulation at baseline. The images were taken during baseline (Visit 2: A, D, and G) and follow-up visits (Visit 6: B, E, H; Visit 7: C, F, and I) and include front, oblique, and lateral views of the abdomen, respectively. These representative images are extracted from the 3D model generated by the QuantifiCare 3D LifeViz^® Body system.

Figure 6 presents ultrasound images illustrating the thickness of subcutaneous fat at baseline, as well as at 4- and 8-week follow-ups after CBL-514 treatment, for the participant with severe fat levels at baseline shown in Figure 5. A reduction in fat thickness from baseline was observed in all 4 scan plots at both follow-up visits.

Figure 6.

Ultrasound measurements of subcutaneous fat thickness of Participant B, a 46-year-old female, recorded at baseline (Visit 2: A [4.06 cm], B [4.20 cm], C [3.90 cm], and D [3.26 cm]), and during the 4-week follow-up (Visit 6: E [2.01 cm], F [2.00 cm], G [1.89 cm], and H [1.91 cm]), and 8-week follow-up (Visit 7: I [2.08 cm], J [2.05 cm], K [1.86 cm], and L [1.89 cm]). The subcutaneous fat thickness was the average thickness of 4 points scanned by ultrasound. To calculate the loss in abdominal fat volume, the cuboid volume formula (volume = height*×basal area^†) was applied. *The height was the average subcutaneous fat thickness measured at 4 points scanned by ultrasound. ^†The basal area was a defined treatment area of 300 cm².

Figure 7 shows the spatial distribution of fat volume loss for the same participant with severe fat levels at baseline, generated by overlapping the baseline and 4-week follow-up 3D models. Greater volumes of fat reduction, indicated by the darker blue areas, are confined to the abdominal region where the treatment area was located.

Figure 7.

Frontal (A) and lateral (B) views illustrating the spatial distribution of fat volume loss in Participant B, a 46-year-old female, captured at 4 weeks postfinal treatment. The darker blue areas represent the larger volume of fat reduction following treatment.

Safety

Nearly all participants (99% overall) reported at least 1 treatment-related TEAE (Supplemental Table 4). Almost all these treatment-related TEAEs were injection site reactions (Table 2), such as erythema, pain, pruritus, and swelling. TEAEs that were considered at least possibly related to the treatment and reported in at least 15% of participants in either group are detailed in Table 2. The majority of treatment-related TEAEs were of mild or moderate severity. Nine participants from the CBL-514 group reported severe TEAEs, all of which involved injection site pain. Overall, of all the 63 participants who reported injection site pain after treatment, 60.3% (38/63) required medication, primarily over-the-counter analgesics. For the majority of participants, the pain resolved within 1 week (90.5%, 57/63). Two participants in the CBL-514 group reported a treatment-related TEAE leading to discontinuation (injection site pain and injection site discoloration). One participant in the CBL-514 group experienced a serious TEAE (peritoneal metastasis) that was deemed unrelated to the study treatment. For 2 participants in the CBL-514 group, both with pre-existing hypercholesterolemia, clinically significant biochemistry values (elevated lipids) were reported at 1 study visit. One of these participants also reported a moderate TEAE of hyperlipidemia that was considered probably related to the study treatment. There were no other significant abnormalities in laboratory tests, physical examinations, vital signs, or ECGs attributed to the study treatment.

Table 2.

Summary of Treatment-Emergent Adverse Events at Least Possibly Related to Study Treatment (Safety Analysis Population)

	No. of participants, n (%)
	CBL-514 600 mg (n = 49)	Placebo (n = 26)
Treatment-related TEAE	48 (98.0)	26 (100.0)
Mild	48 (98.0)	26 (100.0)
Moderate	24 (49.0)	5 (19.2)
Severe	9 (18.4)	0 (0.0)
General disorders and administration site conditions (SOC)	48 (98.0)	26 (100.0)
Injection site erythema (PT)	46 (93.9)	18 (69.2)
Injection site pain (PT)	46 (93.9)	17 (65.4)
Injection site pruritus (PT)	42 (85.7)	11 (42.3)
Injection site swelling (PT)	41 (83.7)	17 (65.4)
Injection site warmth (PT)	41 (83.7)	8 (30.8)
Injection site bruising (PT)	38 (77.6)	22 (84.6)
Injection site discoloration (PT)	35 (71.4)	3 (11.5)
Injection site induration (PT)	30 (61.2)	2 (7.7)
Injection site edema (PT)	10 (20.4)	2 (7.7)

Medical history and AE verbatim terms were coded using the Medical Dictionary for Regulatory Activities (MedDRA version 26.0).

PT, preferred term; SOC, system organ class; TEAE, treatment-emergent adverse event. TEAEs occurring in ≥15% of participants in either group are presented.

DISCUSSION

In this Phase 2 trial, treatment with CBL-514, a novel small-molecule injection lipolysis agent, by subcutaneous injection (up to 4 treatments of up to 600 mg per treatment) resulted in significant abdominal subcutaneous fat volume reduction over the treated body area. The study met all primary and secondary endpoints, and treatment was generally well tolerated. As anticipated, almost all treatment-related TEAEs were injection site reactions, were mild to moderate in severity, and resolved before the end of the study. The non-completion rate was 49.3% overall, most commonly because of loss to follow-up, participant withdrawal, and weight instability, typically weight gain.

Our results suggest that large reductions in abdominal subcutaneous fat volume are achievable with CBL-514 treatment. At the 4-week follow-up assessment after completing treatment, the CBL-514 group had lost >200 mL more fat on average than the placebo group (highly significant LS mean treatment difference), and this difference was maintained until the 8-week follow-up (ITT population). Among the 28 participants in the CBL-514 group who lost ≥150 mL fat volume, 42.9% achieved this after just 1 treatment. The largest fat volume loss recorded in this study was >750 mL in 1 CBL-514-treated participant. Notably, participants exhibited little or no skin laxity following fat loss, apparent in posttreatment images (Figures 4, 5).

Cryolipolysis, FDA-approved for fat reduction in the flanks since 2010 and the abdomen since 2012, offers a comparable noninvasive fat reduction modality. A previous study reported an average fat volume reduction of 264.8 mL in the abdomen and flanks at 12 weeks posttreatment following up to 24 treatment cycles administered over 2 sessions as measured by 3D imaging.¹⁹ Another study, also employing 3D imaging, demonstrated a fat volume reduction of 39.6 mL in the flank region at 2 months posttreatment after a single cryolipolysis cycle.²⁰ The fat volume measurement techniques used in these studies differed from those in our study, which hinders direct comparison. Furthermore, although 3D imaging is a useful tool, it comes with potential limitations in measuring fat volume change, including variability in measurement precision and challenges in maintaining consistent alignment of anatomical landmarks across imaging sessions. Despite these limitations, the overall trend suggests that the fat volume reduction observed in our study appears to be larger. Given that CBL-514 is a minimally-invasive treatment, it may offer an alternative to liposuction or other noninvasive fat removal modalities, thereby broadening the options available to individuals seeking effective localized abdominal fat reduction.

In addition, in the present study, no significant changes from baseline in mean weight and BMI were observed, suggesting that the observed fat volume reductions are primarily attributable to CBL-514 treatment. Moreover, localized fat loss in the treatment area was observed even in participants whose BW gained >1 kg during the study (data not shown).

CBL-514 demonstrated efficacy in targeting subcutaneous fat in the abdomen, an area that is more challenging to address with noninvasive methods because of its size, with an acceptable safety profile. Although 99% of participants experienced at least 1 mild or moderate treatment-related TEAE, most of these were transient injection site reactions. All the treatment-related TEAEs that were graded as severe were administration site conditions, all of which were injection site pain. Only 2 CBL-514 group participants discontinued because of a treatment-related TEAE (injection site pain and injection site discoloration). AEs associated with some injectable treatments for localized fat reduction, such as nerve injury, skin ulceration, or necrosis, were notably absent in this study.

Some limitations should be noted. As this was a Phase 2 study involving only 76 subjects and up to 8 weeks of follow-up, longer follow-up studies are needed to fully understand the long-term safety profile of CBL-514. The non-completion rate was 49.3%, which we attribute to the stringent protocol requirements rather than safety or tolerability issues. In this study, discontinuations were primarily because of non-compliance with study procedures, for example, requirements to maintain a stable weight and strict adherence to treatment and follow-up schedules (Figure 1). Because of the elective nature of cosmetic studies such as this, participants may not perceive a need for further follow-up after having achieved the desired outcomes. Whereas these factors led to the difference in participant numbers between the ITT and the PP populations, the results remained consistent across both groups. Additionally, as the trial mainly included Caucasian participants, future studies are needed to evaluate the treatment's efficacy and safety profile in individuals of other ethnicities. Further investigations of the longevity of CBL-514 treatment effects and its efficacy in other body areas are also warranted.

CONCLUSIONS

Our results indicate that targeted CBL-514 injection lipolysis (2.0 mg/cm²) consistently and significantly reduces subcutaneous abdominal fat (comparable to that achieved with liposuction) and shows a favorable safety profile. Over 75% of CBL-514-treated participants who achieved the target fat volume loss (≥150 mL) required just 1 or 2 treatments. The LS mean of fat volume reduction observed in the CBL-514-treated participants was >300 mL in the PP population, which exceeds double the target fat volume loss. These safety and efficacy results support the further development of CBL-514 as an accessible, noninvasive, and safe option for effective targeted fat reduction in larger body areas.

Supplemental Material

This article contains supplemental material located online at https://doi.org/10.1093/asj/sjaf032.

Disclosures

Drs Gold, Schlessinger, Dayan, DuBois, and Goodman served as principal investigators for this study. Drs Gold and Goodman serve as consultants and investigators for Caliway Biopharmaceuticals (New Taipei City, Taiwan). Dr Goodman serves as a consultant and investigator for AbbVie (Irvine, CA), Galderma (Lausanne, Switzerland), and L’Oreal (Clichy, France), and as a consultant for Dermocosmetica (Melbourne, VIC, Australia). He has received honoraria for lectures, presentations, speakers’ bureaus from Cutera (Brisbane, CA) and AbbVie, and received support for meeting attendance/travel from AbbVie, and served as advisory board member for AbbVie, Galderma, Wesfarmers Health (Perth, WA, Australia), and L’Oreal. Dr Dayan serves as an advisory board member for Caliway Biopharmaceuticals. Dr DuBois serves as a consultant for Accure Acne (Boulder, CO) and as an advisory board member for Medytox (Seoul, Republic of Korea). Ms Ling, Ms Sheu, and Ms Chou are current employees of Caliway Biopharmaceuticals. Ms Ling is a director of Caliway Biopharmaceuticals. Ms Ling, Ms Sheu, and Ms Chou hold shares in Caliway Biopharmaceuticals.

Funding

Caliway Biopharmaceuticals Co., Ltd (New Taipei City, Taiwan) funded the study. Medical writing and editorial support were provided by Tech Observer Asia Pacific Pte. Ltd (Paramus, NJ) and funded by Caliway Biopharmaceuticals Co., Ltd.