Results from a pooled analysis of two European, randomized, placebo-controlled, phase 3 studies of ATX-101 for the pharmacologic reduction of excess submental fat

Abstract

Background: The injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies.

Methods: Patients with unwanted SMF were randomized to receive 1 or 2 mg/cm(2) of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded.

Results: Significantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, and 28.6 % of the placebo recipients; p < 0.001 for both ATX-101 doses vs. placebo) and patient-reported measures (≥1-point improvement in PR-SMFRS: 60.0 and 63.1 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 34.3 % of the placebo recipients; p < 0.001 for both), analyzed alone or in combination, with ATX-101 versus placebo. These improvements correlated moderately with patient satisfaction regarding face and chin appearance (SSRS score ≥4: 60.8 and 65.4 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 29.0 % of the placebo recipients; p < 0.001 for both). In this study, ATX-101 was effective irrespective of gender, age, or body mass index. Reduction in SMF with ATX-101 was confirmed by calliper measurements (p < 0.001 for both doses vs. placebo) and generally did not lead to worsening of skin laxity (SLRS improved or was unchanged: 91.3 and 90.5 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, and 91.6 % of the placebo recipients). Adverse events were mostly transient, mild to moderate in intensity, and localized to the treatment area.

Conclusion: The findings show ATX-101 to be an effective and well-tolerated pharmacologic treatment for SMF reduction.

Trial registration: ClinicalTrials.gov NCT01305577.

Figures

Fig. 1

Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)

Fig. 2

Disposition of all the randomized patients. The patients classified as “prematurely discontinued treatment” still completed the study by completing the follow-up visits. The patients classified as “did not complete study” did not complete the follow-up visits. AE adverse event

Fig. 3

Proportion of treatment responders (≥1-point reduction on the CR-SMFRS) from visit 2 (baseline) to the final follow-up visit (12 weeks after the final treatment). Intention-to-treat population at study visit 7, with the last observation carried forward for patients with missing data. *p < 0.001 versus placebo (Bonferroni–Holm testing procedure). CR-SMFRS Clinician-Reported Submental Fat Rating Scale

Fig. 4

Proportion of patients satisfied with their appearance in association with their face and chin (SSRS score ≥4) at the final follow-up visit (12 weeks after the final treatment). Intention-to-treat population at study visit 7, with the last observation carried forward for patients with missing data. *p < 0.001 versus placebo (Bonferroni–Holm testing procedure). SSRS Subject Self-Rating Scale

Fig. 5

Selected patient images before and after treatment with ATX-101 2 mg/cm2 (a–d) and ATX-101 1 mg/cm2 (e, f). a, e Reproduced from [25]. b, c Reproduced from [24]. Patient photographs published with permission. CR-SMFRS Clinician-Reported Submental Fat Rating Scale, SSRS Subject Self-Rating Scale

Fig. 6

Outcomes and odds ratios (ORs) for ATX-101 1 and 2 mg/cm2, and placebo for primary and secondary clinician- and patient-reported efficacy end points. The graphic representation of ORs shows superiority of ATX-101 over placebo when the 95 % confidence interval (CI) lies completely on the right-hand side of the dotted vertical line. The ORs and p values were determined by binary logistic regression. The intention-to-treat population at study visit 7, with last observation carried forward for patients with missing data, is shown. CI confidence interval, CR-SMFRS Clinician-Reported Submental Fat Rating Scale, PR-SMFRS Patient-Reported Submental Fat Rating Scale, SSRS Subject Self-Rating Scale

Fig. 7

Median duration of adverse events occurring in the treatment area by treatment visit (safety population). See the main text for the corresponding mean values