ATX-101 Treatment Research Articles

Peripheral Nerve Injury After Deoxycholic Acid (ATX-101) Injection in an Experimental Rat Model.

Deoxycholic acid (ATX-101) is a drug administered by subcutaneous injection for local fat reduction. However, ATX-101 treatment has been reported to cause marginal mandibular nerve injury with noticeable functional deficits when targeting submental fat. As a cytolytic agent with some selectivity for adipocytes, ATX-101 may damage the lipid-rich myelin surrounding peripheral nerves. This study seeks to characterize the nerve injection injury from ATX-101 in an experimental rat model. Using a rat sciatic nerve injection model, intrafascicular and extrafascicular injections of deoxycholic acid (ATX-101) were compared to lidocaine (positive control) and saline (negative control). Nerves were harvested at a 2-week endpoint for histomorphometric analysis. Cross-sectional area of nerve injury was significantly increased by ATX-101 injection at 75±15% with intrafascicular ATX-101 (p<0.001), 41±21% with extrafascicular ATX-101 (p<0.01), and 38±20% with positive control lidocaine (p<0.01) compared to 7±13% with negative control saline. Demyelinating injury was a significant mechanism of injury in the affected nerve fibers compared to uninjured nerve fibers (p<0.04), but there was no difference in axon-to-myelin area ratio between the lidocaine and ATX-101 cohorts. After two weeks, Wallerian degeneration was evident with only small regenerating nerve fibers present in the ATX-101-injured groups compared to saline (2.54±0.26um vs 5.03±0.44um, p<0.001) in average width. Deoxycholic acid (ATX-101) is capable of extensive nerve injury in rats. The mechanism of action for ATX-101 does not preferentially target myelin more than other common neurotoxic agents. Appropriate knowledge of surgical anatomy and injection technique is necessary for any practitioners providing ATX-101 injections.

ATX-101 (deoxycholic acid injection) in submental fat reduction: an objective outcome study

**Background**: ATX-101 (deoxycholic acid injection) causes irreversible adipocytolysis and has been studied in multiple clinical trials. It is a Therapeutic Goods and Administration (TGA) approved treatment for minimally invasive reduction of excess submental fat. We present a case series of four consecutive patients who underwent serial ATX-101 (treatment sessions). **Methods**: Each patient underwent between three and four injection sessions with ATX-101 according to manufacturer’s recommendations, spaced six weeks apart. High resolution 3D surface scans were performed pre- and post-ATX-101 treatment and a FACE-Q survey was also completed pre- and post-treatment. **Results**: The submental profiles for each patient were analysed pre- and post-treatment. These demonstrated a mean reduction of the maximum submental fat pad thickness of 4 mm. FACE-Q surveys showed improvement in patient satisfaction in their submental ap-pearance. Apart from pain associated with the injection of ATX-101, we did not encounter other adverse reactions in our patient group.**Conclusions**: This is the first study to analyse the outcome of ATX-101 using high resolution surface scans of the submental area. The reduction in thickness of the submental fat by 4 mm demonstrates clinical effectiveness of ATX-101 in treatment of excess submental fat six weeks after treatment.

Submental Area Treatment with ATX-101: Relationship of Mechanism of Action, Tissue Response, and Efficacy.

A narrative review of references relevant to the mechanism of action of ATX-101 and its relationship to efficacy and inflammatory adverse events was conducted. When injected into subcutaneous fat, deoxycholic acid physically disrupts adipocyte cell membranes, leading to local adipocytolysis, cell death, and a mild, local inflammatory reaction consisting of macrophage infiltration and fibroblast recruitment. At Day 28 postinjection, inflammation largely resolves, and key histologic features include fibrotic septal thickening, neovascularization, and atrophy of fat lobules. Based on the mechanism of action of ATX-101 and the demonstrated inflammatory response, localized inflammation and swelling are expected following treatment. Indeed, postinjection swelling and other local injection-site events, including pain, erythema, and bruising, are common during and after treatment. Because of inflammatory sequelae following injection, reduction in submental fat is gradual and may require months before the full response is apparent. Patients may also require multiple treatment sessions to achieve their treatment goals. Repeated treatments may result in less pain and swelling over time owing to a combination of factors, including less target tissue allowing for lower doses/injection volumes, persistent numbness, and greater tissue integrity from thickened fibrous septa. Physicians can manage expectations by counseling patients that, based on the mechanism of action of ATX-101 and data from pivotal clinical trials, ATX-101 treatment results in localized inflammation/swelling and gradual submental fat reduction. Patient education about common local adverse events is critical.

Best Clinical Practices with ATX-101 for Submental Fat Reduction: Patient-related Factors and Physician Considerations.

Background:Submental fat can be reduced with ATX-101 (deoxycholic acid injection), a customizable and minimally invasive alternative to liposuction. In the years since its approval, the treatment patterns of ATX-101 have evolved.Methods:A panel of experienced physicians from the United States gathered to generate best practices for the use of ATX-101 in submental contouring.Results:The expert panel provided their insights on appropriate patient selection, managing patient expectations of ATX-101 treatment outcomes, and adverse events, and guidance on ATX-101 administration for optimal outcomes are presented here.Conclusion:These best clinical practices on the use of ATX-101 for the reduction of submental fat should enable physicians to enhance the patient treatment experience and outcomes.

Abstract 87: Improvements In Jowl Fat Following ATX-101 (Deoxycholic Acid) Injection: Updated Results From A Single-Site Study

Purpose: Jowl fat overhang can reduce jawline definition and is a component of the aging face. The most common treatment to reduce jowl fat is liposuction. ATX-101 (deoxycholic acid) injection, a minimally-invasive treatment approved for submental fat reduction, may also be an effective treatment for jowl fat. This study evaluates the efficacy and safety of ATX-101 treatment for reducing jowl fat and provides an update to a previous study, accounting for longer-term follow-up and a larger cohort of patients. Methods: In this ongoing, prospective, single-site study, 125 patients were treated for excess jowl fat with ATX-101 (area-adjusted dose: 2 mg/cm2). Eligible patients had pinchable fat on the jawline and relatively minimal skin laxity in the jowl. Depending on the size of the treatment area, ATX-101 injections of 0.2 ml spaced 1.0 cm apart or 0.1 ml spaced 0.50 to 0.75 cm apart were administered. Improvement in jowl appearance was assessed in-person by the clinician ≥6 months after last treatment. Independent assessments were also made by the patient and two blinded plastic surgeons using standardized pre- and post-treatment photography. Safety was evaluated via adverse events (AEs). Results: Since the previous report, 59 additional patients underwent treatment (N = 125). Patients underwent a mean of 2.3 treatments to the bilateral jowls. Mean injection volume administered per treatment was 0.8 ml/jowl. The majority of patients (98%) experienced an improvement in jowl appearance. Common AEs were injection-site edema, numbness, tenderness, and bruising. Injection-site marginal mandibular nerve paresis and alopecia were experienced by three patients each; all events resolved without sequelae. Conclusion: ATX-101 effectively reduced jowl fat and was well-tolerated in this cohort. Notably, several patients received ATX-101 injection to the jowls in isolation of submental fullness. Care should be taken when injecting ATX-101 into jowl fat to avoid underlying anatomic structures such as the marginal mandibular nerve.

Improvement in Jowl Fat following ATX-101 Treatment: Results from a Single-Site Study.

Background:Jowl fat overhang can reduce jawline definition. The most common treatment to reduce jowl fat is liposuction. ATX-101 (deoxycholic acid injection), a minimally invasive treatment approved for submental fat reduction, may also be an effective treatment for jowl fat. The current study evaluated the efficacy and safety of ATX-101 treatment for reducing jowl fat.Methods:In this prospective single-site study, 66 adults were treated for excess jowl fat with ATX-101 (area-adjusted dose: 2 mg/cm2). Eligible patients had pinchable fat on the jawline and relatively minimal skin laxity in the jowl. Depending on the size of the treatment area, ATX-101 injections of 0.2 ml spaced 1.0 cm apart or 0.1 ml spaced 0.50 to 0.75 cm apart were administered. Improvement in jowl appearance was assessed 6 months or more after the last treatment in person by the clinician. Improvement was also assessed by the patient and two independent plastic surgeons using blinded before/after treatment photographs. Safety was evaluated via adverse events.Results:The mean number of ATX-101 treatments received was 1.8, with a mean injection volume of 0.8 ml per treatment per jowl. The majority of patients (98 percent) experienced an improvement in jowl appearance. Common adverse events were injection-site edema, numbness, tenderness, and bruising. Injection-site marginal mandibular nerve paresis and alopecia were experienced by three patients each; all events resolved without sequelae.Conclusions:ATX-101 effectively reduced jowl fat and was well tolerated in this small cohort. Care should be taken when injecting ATX-101 into jowl fat to avoid underlying anatomic structures such as the marginal mandibular nerve.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.

Novel Expanded Safe Zone for Reduction of Submental Fullness with ATX-101 Injection.

Background:ATX-101 (deoxycholic acid injection; Kybella) provides an approved nonsurgical treatment option for reduction of submental fullness caused by submental fat. Current one-size-fits-all recommendations for the use of ATX-101 limit treatment to a central area, which may not provide complete resolution of submental fat for some patients. An expanded safe zone is described, allowing for individualized, comprehensive treatment of submental fat with ATX-101 according to each patient’s anatomy and desired outcomes.Methods:A retrospective review was conducted of patients treated with ATX-101 for excess submental fat between June of 2015 and December of 2016 at a single plastic surgery practice. The expanded safe zone was developed to isolate the distinct fat compartments of the submental area and includes a no-treatment zone to avoid the marginal mandibular nerve. The extent of ATX-101 treatment required in each zone was determined by assessment of subcutaneous adipose tissue. A 1-cm grid was used to mark the treatment area before injection of ATX-101 (2 mg/cm2). Improvement (defined as decreased palpable and/or visible submental fullness) was determined at least 4 months after the final treatment. Adverse events were recorded at each visit and reported by patients by means of telephone.Results:Overall, 167 patients were included in this analysis. Improvement in submental fullness was achieved in 160 of 167 patients (95.8 percent). The majority of adverse events consisted of temporary injection-site edema, numbness, and tenderness.Conclusion:An understanding of submental anatomy and careful assessment of each patient’s submental fat allows for individualized treatment with ATX-101 beyond the central region of the neck without increased risk of adverse events.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.

Efficacy and safety of ATX-101 as a treatment for submental fullness: A retrospective analysis of two aesthetic practices.

Submental fullness (SMF) is a common cosmetic concern that can have negative impact on one's self-esteem. ATX-101 has shown promise as a minimally invasive treatment for SMF correction in clinical trials. To assess the safety and efficacy of ATX-101 for SMF correction. This was a retrospective review of 90 patients from two aesthetic practices who received ATX-101 injections for SMF (January 2016-August 2017). There were no exclusion criteria. Initial SMF severity was assigned using standardized photographs and a validated 5-point scale. Eighty one patients subsequently answered questionnaires regarding improvement, satisfaction, and adverse effects. Degree of SMF correction was also evaluated by the investigator and a blinded reviewer. Eighty one patients (mean initial submental fullness severity 1.6) received a mean of 1.84 ATX-101 treatment sessions using a median of 2.0 vials per treatment (mean 3.02, range 1-9). Mean Physician Global Aesthetic Improvement Scale scores were 2.73 and 2.25, after the first and second treatments, respectively (P=.04). Mean Subject Goal Aesthetic Improvement Scale scores were 2.7 and 2.25 after the first and second treatments, respectively (P=.01). Sixty-seven percentage of patients were "somewhat" or "very" satisfied. Adverse events were transient and limited to the treatment area. Patients achieved progressive improvement in SMF after the 1st and 2nd treatments, as judged by patients themselves, investigators, and blinded evaluators. These results of SMF correction suggest that significant benefit can be obtained with proper dosing at the initial visit. These data support the efficacy and safety profile of ATX-101 use for SMF correction.

Injection of an Adipocytolytic Agent for Reduction of Excess Periaxillary Fat.

BackgroundThe principal current treatment options for reduction of excess anterior periaxillary fat (APAF) are invasive procedures such as excision and liposuction.ObjectivesThe aim of this study was to evaluate the efficacy and safety of ATX-101 (deoxycholic acid injection) as a treatment to reduce APAF.MethodsIn this retrospective study, 12 women with periaxillary fullness underwent ATX-101 treatment. Patients were examined to confirm that fullness was due to excess APAF and sufficient subcutaneous fat was present to warrant treatment. Before treatment, the lateral and medial borders of the treatment area were identified and marked. A 1-cm grid was placed to guide the placement of the ATX-101 injections. Reduction in APAF was based on visual assessment and palpation by the clinician, and assessment of before/after patient photographs by the patient and 2 blinded plastic surgeons; all had to agree that APAF reduction had occurred. Patient satisfaction was also assessed. Safety was evaluated in terms of adverse events (AEs).ResultsPatients underwent a mean of 1.8 ATX-101 treatments; 5 patients received 1 treatment, whereas 7 received multiple treatments. Ten patients achieved a reduction in APAF and were satisfied with treatment. One patient was satisfied after 1 treatment but did not return for posttreatment photographs. One patient did not show any noticeable reduction in APAF after 1 treatment; however, this patient was satisfied and additional treatments are planned. Common AEs included injection-site numbness, edema, and tenderness that lasted for a mean of 18.6, 6.0, and 4.5 days, respectively.ConclusionsATX-101 effectively reduced APAF and was generally well tolerated in this small cohort. Larger prospective studies are needed to confirm these findings.Level of Evidence: 4

Efficacy and Safety of ATX-101 by Treatment Session: Pooled Analysis of Data From the Phase 3 REFINE Trials.

BackgroundATX-101 (deoxycholic acid injection) is the only injectable drug approved for submental fat (SMF) reduction. In the phase 3 REFINE trials, adults with moderate or severe SMF who were dissatisfied with the appearance of their face/chin were eligible to receive up to 6 treatment sessions with ATX-101 (2 mg/cm2) or placebo. Primary and secondary endpoints, evaluated at 12 weeks after last treatment, significantly favored ATX-101 supporting its efficacy for reducing SMF and the psychological impact of SMF, and increasing satisfaction with the appearance of the face/chin.ObjectivesTo evaluate the efficacy and safety of ATX-101 by treatment session.MethodsThis post hoc analysis used pooled data from the REFINE trials to evaluate efficacy endpoints and adverse events following each treatment session to further characterize the ATX-101 treatment response and safety profile.ResultsIn both treatment groups, mean injection volume declined over subsequent treatment sessions, though more markedly in the ATX-101 group. The majority of ATX-101–treated patients achieved a ≥1-grade improvement in SMF within 2 to 4 treatment sessions based on either clinician or patient assessment. Furthermore, 19.1% of ATX-101–treated patients (vs 3.9% of placebo-treated patients) received fewer than 6 treatment sessions owing to patient satisfaction with treatment or lack of sufficient SMF for further treatment. In both treatment groups, the incidence/severity of common injection-site adverse events declined over subsequent treatment sessions.ConclusionsAlthough up to 6 treatment sessions were permitted in the REFINE trials, most ATX-101–treated patients achieved an improvement in SMF within 2 to 4 treatment sessions.Level of Evidence: 3

ATX-101 (Deoxycholic Acid Injection) Treatment in Men: Insights From Our Clinical Experience.

Excess submental fat (SMF), also called a double chin, is an area of concern for men that can be addressed clinically. ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada, Australia, and various European countries) is the first injectable approved for reduction of SMF. To share the authors' clinical experience using ATX-101 in men with submental fullness and offer insights regarding how this treatment may be presented to men as an option to improve their submental profile. Retrospective review of the authors' medical records for male patients treated with ATX-101. To allow for fewer ATX-101 treatments, it is recommended that a large surface area be treated at the first session. The positive changes and outcomes achieved with ATX-101 build confidence between the physician and patient, which often leads to male patients seeking other aesthetic treatments to improve their overall appearance. ATX-101 treatment is often an effective introduction to aesthetic medicine for men.

Prevention and Management of Injection-Related Adverse Effects in Facial Aesthetics: Considerations for ATX-101 (Deoxycholic Acid Injection) Treatment

ATX-101 (deoxycholic acid injection; Kythera Biopharmaceuticals, Inc. [an affiliate of Allergan plc, Dublin, Ireland]) was approved in 2015 in the United States (Kybella) and Canada (Belkyra) for submental fat reduction. As expected, injection-site reactions such as pain, swelling, and bruising, which were mostly mild or moderate and transient, were common adverse events (AEs) reported in clinical trials. An exploratory Phase 3b study investigating interventions for management of injection-site AEs associated with ATX-101 treatment was recently completed. Based on its results, literature review, and our clinical experiences, we have put forward considerations for management of AEs associated with ATX-101 treatment in clinical practice. Pretreatment with oral ibuprofen and/or acetaminophen an hour before treatment and preinjection with epinephrine-containing buffered lidocaine 15 minutes before treatment can help with management of pain and bruising. Cold application to the treated area before and immediately after the procedure may help to reduce pain (if local anesthetic preinjection is not performed) and swelling. Discontinuing medications/supplements that result in increased anticoagulant or antiplatelet activity 7 to 10 days before ATX-101 treatment, when possible, can reduce the risk of bruising. In summary, injection-site AEs associated with ATX-101 treatment can be effectively managed with commonly used interventions.

Overview of ATX-101 (Deoxycholic Acid Injection): A Nonsurgical Approach for Reduction of Submental Fat.

In 2015, ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) was approved as a first-in-class injectable drug for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat. ATX-101 has been evaluated in a clinical development program that included 18 Phase 1 to 3 studies supporting the current indication. Since 2007, the toxicity and safety profiles of ATX-101 have been characterized in numerous preclinical studies, its pharmacokinetics, pharmacodynamics, and optimal treatment paradigm have been defined in multiple Phase 1 and 2 studies, and its efficacy and clinical safety have been confirmed in 4 large Phase 3 trials (2 conducted in Europe and 2 in the United States and Canada [REFINE-1 and REFINE-2]). As subcutaneous injection of deoxycholic acid has been shown to cause adipocytolysis, the reduction in submental fat achieved after ATX-101 treatment is expected to be long lasting. This prediction is confirmed by data from long-term follow-up studies of up to 4 years after last treatment with ATX-101, which demonstrate that the treatment response is maintained over time in most subjects. ATX-101 offers a durable, minimally invasive alternative to liposuction and surgery for addressing submental fullness.

ATX-101 treatment offers long-term durability of submental fat reduction: Preliminary follow-up study results of subjects from phase II studies

ATX-101 treatment offers long-term durability of submental fat reduction: Preliminary follow-up study results of subjects from phase II studies