Imcivree

POMC, PCSK1, and LEPR Deficiency

The safety and efficacy of setmelanotide for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to POMC, PCSK1, or LEPR deficiency were assessed in 2 identically designed, 1-year, open-label studies, each with an 8-week, double-blind withdrawal period.

• Study 1 (NCT02896192) enrolled patients with obesity and genetically confirmed or suspected POMC or PCSK1 deficiency.

• Study 2 (NCT03287960) enrolled patients with obesity and genetically confirmed or suspected LEPR deficiency.

In both studies:

• The local genetic testing results were centrally confirmed using Sanger sequencing. 

• Adult patients had a body mass index (BMI) of ≥30 kg/m². 

• Weight in pediatric patients was ≥95th percentile using growth chart assessments.

Efficacy analyses were conducted in 21 patients (10 in Study 1; 11 in Study 2) who had completed at least 1 year of treatment at the time of a prespecified data cutoff.

Of the 21 patients included in the efficacy analysis in Studies 1 and 2, 62% were adults and 38% were pediatric patients ≤16 years.

• In Study 1, 50% of patients were female, 70% were White, and the median BMI was 40 kg/m² (range: 26.6-53.3) at baseline.

• In Study 2, 73% of patients were female, 91% were White, and the median BMI was 46.6 kg/m² (range: 35.8-64.6) at baseline.

The primary end point for both studies assessed the percentage of patients with at least 10% weight loss; secondary end points included the mean percent reduction from baseline of body weight and hunger score responder analysis on an 11-point scale from 0 (“not hungry at all”) to 10 (“hungriest possible”).

In Study 1, results showed 80% (n=8/10) of patients met the primary end point achieving at least 10% weight loss from baseline to 1 year (95% CI: 44.4, 97.5; P <.0001); the mean reduction from baseline in body weight was -23.12% (95% CI: -31.9, -14.4; P =.0003), and the median reduction in hunger score was -2.0.

In Study 2, results showed 46% (n=5/11) of patients met the primary end point achieving at least 10% weight loss from baseline to 1 year (95% CI: 16.8, 76.6; P =.0002); the mean reduction from baseline in body weight was -9.65% (95% CI: -16.0, -3.3; P =.0074), and the median reduction in hunger score was -3.4.

Bardet-Biedl Syndrome

The safety and efficacy of setmelanotide for chronic weight management in adult and pediatric patients aged 6 years and older with obesity and a clinical diagnosis of Bardet-Biedl syndrome (BBS) were assessed in a 66-week clinical study, which included a 14-week randomized, double-blind, placebo-controlled period and a 52-week open-label period (Study 3 [NCT03746522]). In the study, enrolled adult patients had a BMI of ≥30 kg/m² and pediatric patients had weight ≥97th percentile using growth chart assessments.

Eligible patients were entered into a 14-week, randomized, double-blind, placebo-controlled treatment period (Period 1) in which patients received setmelanotide or placebo, followed by a 52- week open-label treatment period (Period 2) in which all patients received setmelanotide. 

Efficacy analyses were conducted in 44 patients at the end of Period 1 (Week 14, placebo-controlled data) and in 31 patients during the active-treatment period, defined as the period from randomization to Week 52 in patients initially randomized to setmelanotide, and from Week 14 to Week 66 in patients initially randomized to placebo. Analyses of the active-treatment period include patients who had either completed 52 weeks from the start of setmelanotide treatment or discontinued the study early at the time of the prespecified data cutoff.

A total of 44 patients with obesity and a clinical diagnosis of BBS were enrolled; 50% were adults, 32% were aged 12 to <18 years, and 18% were aged 6 to <12 years; 46% were male; 77% were White, 5% were Black, 2% were Asian, and 16% had an unknown or not reported race; 2% were Hispanic or Latino and 14% had an unknown or not reported ethnicity; and the mean BMI was 41.5 kg/m² (range: 24.4-66.1 kg/m²) at baseline.

In Study 3, results showed the mean percent change in BMI after 52 weeks of Imcivree treatment was -7.9% (95% CI: -10.4, -5.5), 61.3% (95% CI: 42.2, 78.2) of patients achieved a ≥5% BMI decrease from baseline, and 38.7% (95% CI: 21.8, 57.8) had a ≥10% decrease in BMI.

During the 14-week double-blind, placebo-controlled portion of Study 3 (Period 1), there was a statistically significant difference in BMI reduction between the setmelanotide-treated group and the placebo-treated group (placebo-adjusted difference: -4.5 [95% CI: -6.5, -2.5]).

Additionally, hunger scores decreased in setmelanotide-treated patients during the 14-week placebo-controlled period and during the open-label treatment period.