ATX-101: ‘You’re gonna like your new chin’

ISTANBUL – Both clinicians and patients gave favorable marks to a novel injectable pharmacologic treatment for removal of unwanted submental fat – the unsightly double chin – in two phase III randomized trials presented at the annual congress of the European Academy of Dermatology and Venereology.

The investigational chin-fat buster, known as ATX-101, is a proprietary purified synthetic form of deoxycholic acid. Upon injection directly into the submental fat, ATX-101 lyses adipocytes by disrupting their cell membranes.

There is an unmet need for a rigorously studied prescription product for nonsurgical treatment of excess submental fat. Not everyone with a double chin is interested in or a good candidate for the established surgical procedures, observed Dr. Berthold Rzany, a dermatologist at Charité University Hospital, Berlin, who presented a 363-patient, randomized, placebo-controlled phase III trial at the meeting. Participants had to have a body mass index no higher than 30 kg/m², dissatisfaction with the appearance of their submental area, and a physician rating of moderate to severe submental fat. Three-quarters of the subjects were women, with a mean age of 46 years and a mean BMI of 25.7 kg/m².

One of the two primary efficacy endpoints required at least a 1-point improvement on the 0- to 4-point Clinician-Reported Submental Fat Rating Scale as assessed 12 weeks after the final treatment. This was achieved in 59% of patients randomized to ATX-101 at a dose of 1mg/cm² and 65% at 2 mg/cm², both significantly higher rates than the 23% in placebo-treated controls.

The other primary endpoint required a high level of patient satisfaction with the appearance of their face and chin after treatment as expressed in a Subject Self-Rating Scale score of 4 or more on the 0-6 scale. This endpoint was achieved in 53% of patients treated with ATX-101 at 1 mg/cm², 66% who received the agent at 2 mg/cm², and 29% of the placebo group.

ATX-101-treated patients were also significantly more likely to report perceived improvement in the visual and psychological impact of their submental fat. For example, 74% of patients who received ATX-101 at 1 mg/cm² and 80% at 2 mg/cm² reported improved definition between their chin and neck, compared with baseline and compared with 28% of placebo-treated controls. In addition, 32% of patients who received the lower dose of ATX-101 and 39% who got the higher dose characterized their submental fat as "a great deal better," compared with baseline, as did a mere 7% of controls.

Also, patients who received ATX-101 reported 12 weeks post treatment that they looked less overweight and were less bothered by and self-conscious about their submental fat, compared with controls.

Treatment-emergent induration, redness, bruising, numbness, and/or swelling variously occurred in one-third to two-thirds of ATX-101 recipients. All of these adverse events were more common than in placebo-treated controls. However, the events were transient and mostly mild or moderate in intensity. The exception was injection site pain, which occurred in roughly 80% of ATX-101-treated patients and was mostly moderate to severe, although it lasted a median of only 1 day, according to Dr. Rzany.

The ATX-101 treatment regimen entails up to 50 2-mL fixed-dose subcutaneous injections 1 cm apart per treatment session. Up to four treatment sessions were permitted, each separated by a minimum of 4 weeks.

In a separate presentation, Dr. Benjamin Ascher reported on 360 randomized patients who participated in the other phase III clinical trial. The two studies had the same design and endpoints.

An improvement of at least 1 point on the Clinician-Reported Submental Fat Rating Scale occurred in 58% of patients randomized to ATX-101 at the 1 mg/cm² dose, 62% of those who received the higher dose, and 35% on placebo. Moreover, 68% of patients who got ATX-101 at 1 mg/cm² were satisfied with their resultant appearance as reflected in a Subject Self-Rating Scale score of at least 4. So were 65% of those who received the higher dose and 29% of placebo-treated controls. As in the previously mentioned study, indices of self-image and psychological well being were also improved following the aesthetic therapy. Treatment-related adverse events were mostly transient and mild to moderate in intensity, according to Dr. Ascher, who is in the private practice of aesthetic surgery in Paris.

Both phase III studies were supported by Bayer HealthCare and KYTHERA Biopharmaceuticals. Dr. Rzany and Dr. Ascher serve as advisers to the companies.

bjancin@frontlinemedcom.com

ISTANBUL – Both clinicians and patients gave favorable marks to a novel injectable pharmacologic treatment for removal of unwanted submental fat – the unsightly double chin – in two phase III randomized trials presented at the annual congress of the European Academy of Dermatology and Venereology.

The investigational chin-fat buster, known as ATX-101, is a proprietary purified synthetic form of deoxycholic acid. Upon injection directly into the submental fat, ATX-101 lyses adipocytes by disrupting their cell membranes.

There is an unmet need for a rigorously studied prescription product for nonsurgical treatment of excess submental fat. Not everyone with a double chin is interested in or a good candidate for the established surgical procedures, observed Dr. Berthold Rzany, a dermatologist at Charité University Hospital, Berlin, who presented a 363-patient, randomized, placebo-controlled phase III trial at the meeting. Participants had to have a body mass index no higher than 30 kg/m², dissatisfaction with the appearance of their submental area, and a physician rating of moderate to severe submental fat. Three-quarters of the subjects were women, with a mean age of 46 years and a mean BMI of 25.7 kg/m².

One of the two primary efficacy endpoints required at least a 1-point improvement on the 0- to 4-point Clinician-Reported Submental Fat Rating Scale as assessed 12 weeks after the final treatment. This was achieved in 59% of patients randomized to ATX-101 at a dose of 1mg/cm² and 65% at 2 mg/cm², both significantly higher rates than the 23% in placebo-treated controls.

The other primary endpoint required a high level of patient satisfaction with the appearance of their face and chin after treatment as expressed in a Subject Self-Rating Scale score of 4 or more on the 0-6 scale. This endpoint was achieved in 53% of patients treated with ATX-101 at 1 mg/cm², 66% who received the agent at 2 mg/cm², and 29% of the placebo group.

ATX-101-treated patients were also significantly more likely to report perceived improvement in the visual and psychological impact of their submental fat. For example, 74% of patients who received ATX-101 at 1 mg/cm² and 80% at 2 mg/cm² reported improved definition between their chin and neck, compared with baseline and compared with 28% of placebo-treated controls. In addition, 32% of patients who received the lower dose of ATX-101 and 39% who got the higher dose characterized their submental fat as "a great deal better," compared with baseline, as did a mere 7% of controls.

Also, patients who received ATX-101 reported 12 weeks post treatment that they looked less overweight and were less bothered by and self-conscious about their submental fat, compared with controls.

Treatment-emergent induration, redness, bruising, numbness, and/or swelling variously occurred in one-third to two-thirds of ATX-101 recipients. All of these adverse events were more common than in placebo-treated controls. However, the events were transient and mostly mild or moderate in intensity. The exception was injection site pain, which occurred in roughly 80% of ATX-101-treated patients and was mostly moderate to severe, although it lasted a median of only 1 day, according to Dr. Rzany.

The ATX-101 treatment regimen entails up to 50 2-mL fixed-dose subcutaneous injections 1 cm apart per treatment session. Up to four treatment sessions were permitted, each separated by a minimum of 4 weeks.

In a separate presentation, Dr. Benjamin Ascher reported on 360 randomized patients who participated in the other phase III clinical trial. The two studies had the same design and endpoints.

An improvement of at least 1 point on the Clinician-Reported Submental Fat Rating Scale occurred in 58% of patients randomized to ATX-101 at the 1 mg/cm² dose, 62% of those who received the higher dose, and 35% on placebo. Moreover, 68% of patients who got ATX-101 at 1 mg/cm² were satisfied with their resultant appearance as reflected in a Subject Self-Rating Scale score of at least 4. So were 65% of those who received the higher dose and 29% of placebo-treated controls. As in the previously mentioned study, indices of self-image and psychological well being were also improved following the aesthetic therapy. Treatment-related adverse events were mostly transient and mild to moderate in intensity, according to Dr. Ascher, who is in the private practice of aesthetic surgery in Paris.

Both phase III studies were supported by Bayer HealthCare and KYTHERA Biopharmaceuticals. Dr. Rzany and Dr. Ascher serve as advisers to the companies.

bjancin@frontlinemedcom.com

ISTANBUL – Both clinicians and patients gave favorable marks to a novel injectable pharmacologic treatment for removal of unwanted submental fat – the unsightly double chin – in two phase III randomized trials presented at the annual congress of the European Academy of Dermatology and Venereology.

The investigational chin-fat buster, known as ATX-101, is a proprietary purified synthetic form of deoxycholic acid. Upon injection directly into the submental fat, ATX-101 lyses adipocytes by disrupting their cell membranes.

There is an unmet need for a rigorously studied prescription product for nonsurgical treatment of excess submental fat. Not everyone with a double chin is interested in or a good candidate for the established surgical procedures, observed Dr. Berthold Rzany, a dermatologist at Charité University Hospital, Berlin, who presented a 363-patient, randomized, placebo-controlled phase III trial at the meeting. Participants had to have a body mass index no higher than 30 kg/m², dissatisfaction with the appearance of their submental area, and a physician rating of moderate to severe submental fat. Three-quarters of the subjects were women, with a mean age of 46 years and a mean BMI of 25.7 kg/m².

One of the two primary efficacy endpoints required at least a 1-point improvement on the 0- to 4-point Clinician-Reported Submental Fat Rating Scale as assessed 12 weeks after the final treatment. This was achieved in 59% of patients randomized to ATX-101 at a dose of 1mg/cm² and 65% at 2 mg/cm², both significantly higher rates than the 23% in placebo-treated controls.

The other primary endpoint required a high level of patient satisfaction with the appearance of their face and chin after treatment as expressed in a Subject Self-Rating Scale score of 4 or more on the 0-6 scale. This endpoint was achieved in 53% of patients treated with ATX-101 at 1 mg/cm², 66% who received the agent at 2 mg/cm², and 29% of the placebo group.

ATX-101-treated patients were also significantly more likely to report perceived improvement in the visual and psychological impact of their submental fat. For example, 74% of patients who received ATX-101 at 1 mg/cm² and 80% at 2 mg/cm² reported improved definition between their chin and neck, compared with baseline and compared with 28% of placebo-treated controls. In addition, 32% of patients who received the lower dose of ATX-101 and 39% who got the higher dose characterized their submental fat as "a great deal better," compared with baseline, as did a mere 7% of controls.

Also, patients who received ATX-101 reported 12 weeks post treatment that they looked less overweight and were less bothered by and self-conscious about their submental fat, compared with controls.

Treatment-emergent induration, redness, bruising, numbness, and/or swelling variously occurred in one-third to two-thirds of ATX-101 recipients. All of these adverse events were more common than in placebo-treated controls. However, the events were transient and mostly mild or moderate in intensity. The exception was injection site pain, which occurred in roughly 80% of ATX-101-treated patients and was mostly moderate to severe, although it lasted a median of only 1 day, according to Dr. Rzany.

The ATX-101 treatment regimen entails up to 50 2-mL fixed-dose subcutaneous injections 1 cm apart per treatment session. Up to four treatment sessions were permitted, each separated by a minimum of 4 weeks.

In a separate presentation, Dr. Benjamin Ascher reported on 360 randomized patients who participated in the other phase III clinical trial. The two studies had the same design and endpoints.

An improvement of at least 1 point on the Clinician-Reported Submental Fat Rating Scale occurred in 58% of patients randomized to ATX-101 at the 1 mg/cm² dose, 62% of those who received the higher dose, and 35% on placebo. Moreover, 68% of patients who got ATX-101 at 1 mg/cm² were satisfied with their resultant appearance as reflected in a Subject Self-Rating Scale score of at least 4. So were 65% of those who received the higher dose and 29% of placebo-treated controls. As in the previously mentioned study, indices of self-image and psychological well being were also improved following the aesthetic therapy. Treatment-related adverse events were mostly transient and mild to moderate in intensity, according to Dr. Ascher, who is in the private practice of aesthetic surgery in Paris.

Both phase III studies were supported by Bayer HealthCare and KYTHERA Biopharmaceuticals. Dr. Rzany and Dr. Ascher serve as advisers to the companies.

bjancin@frontlinemedcom.com