Injectable polidocanol targets double chins with remarkable efficacy

Injections with polidocanol (10XB-101) help dissolve the pocket of excess fat under the chin, with a faster onset of action and fewer side effects relative to synthetic deoxycholic acid compound (ATX-101) injections, according to the results of a phase IIb study.

Intention-to-treat analysis showed that polidocanol at two tested doses (3% and 4.5%) outperformed ATX-101 at reducing submental fat in terms of the composite endpoint of a ≥2-grade improvement in Clinician Submental Fat Score (CSFS) and Patient Submental Fat Score (PSFS) at 4 weeks after the final treatment, reported lead study author Dr Kavita Darji, a board-certified dermatologist and laser and cosmetic dermatologic surgery fellow at Cosmetic Laser Dermatology in San Diego, California, US.

The proportion of participants who achieved the composite endpoint was 62 percent with 3% polidocanol and 54 percent with the 4.5% dose versus 16 percent with ATX-101* (p<0.01 for both). [Darji K, et al, AAD 2024; Plast Reconst Surg 2014;134(4S-1):123]

In the completer population, a larger proportion of polidocanol-treated participants experienced a ≥2-grade improvement in CSFS and PSFS (80 percent with the 3% dose and 79 percent with the 4.5% dose; p<0.01 for both).

The numbers in the intention-to-treat and completer populations translate to 2 to 5 times higher treatment success rate with polidocanol than with ATX-101, indicating that the injectable drug was effective at reducing submental fat from the perspective of both the treating physicians and the patients themselves, according to Darji.

Additionally, when compared with ATX-101, polidocanol delivered faster results, with an average 1-grade improvement in the appearance of submental fat occurring after only two treatments, she continued. Half of the participants had achieved 2-grade improvements by the fourth treatment.

Tolerability

Polidocanol had a favourable safety profile. Darji noted that almost all (98 percent) local skin reactions were mild (rated as 0 or 1), and there were no safety issues found in blood tests or electrocardiogram assessments. One serious event occurred, which was a case of myocardial infarction that was successfully resolved.

Notably, there was a more than 50-percent reduction in the frequency of side effects—including bruising, oedema, pain, induration, nodules, and numbness—with polidocanol versus ATX-101. According to Darji, severe oedema cases were especially fewer in the present study than in previous ATX-101 trials. [Plast Reconstr Surg Glob Open 2016;4:e1155]

With polidocanol having reduced side effects both in terms of frequency and severity, shorter treatment intervals may be possible, Darji added. Treated individuals can typically resume their normal activities within 1-3 days, minimizing disruption to their daily routines.

In light of the positive findings, Darji underscored a potential opportunity to expand polidocanol treatment to other anatomic areas.

“Injectable polidocanol is a synthetic nonionic detergent that is US Food and Drug Administration-approved for sclerotherapy and has been demonstrated to be an adipolytic. [This] polidocanol solution in a novel formulation shows less inflammation and release of cytokines TNF alpha and MCP-1 by macrophages than [ATX-101],” she said.

In the phase IIb study, 51 participants were randomly assigned to treatment with polidocanol at a dose of 2%, 3%, or 4.5% or the vehicle control. Each participant received up to six treatments, involving approximately 50 injections of 0.2 ml each, administered 4 weeks apart.

The completer population comprised 40 participants who received at least four treatments, had completed the treatments per protocol, and showed no significant protocol deviations.

*Data obtained from a pooled analysis of the pivotal phase III REFINE-1 and -2 trials