AbbVie announced positive topline results from the multiple ascending dose part of its Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous ABBV-295, in adults with a mean body mass index (BMI) of less than 30 kg/m2. ABBV-295 is a long-acting amylin analog that represents a mechanistically distinct class from incretin-based therapies such as GLP-1 and GIP receptor agonists. Study enrollment mostly comprised male participants (88.3%).
Different doses (2-14 mg), titrations and dose frequencies were tested in the study. ABBV-295 was generally well tolerated across all dose levels evaluated. The most commonly reported adverse events were gastrointestinal disorders, which were mostly mild, and predominantly occurred during the first 6 weeks of treatment.
ABBV-295 demonstrated clinically meaningful, dose-dependent reductions in body weight from baseline, over a 12-13-week treatment period. In the ABBV-295 treated groups dose-dependent least-squares (LS) mean percentage change in body weight ranged from -7.75% to -9.79% at week 12 (for weekly dosing groups), to -7.86% to -9.73% at week 13 (for every other week dosing group and monthly dosing group after week 5), compared to -0.26% and -0.25% in the placebo group at week 12 and week 13, respectively. Results from the single ascending doses (SAD) part and other cohorts from the MAD part of the study were announced previously.
Full data from the study will be presented at a future scientific conference. Summary of Phase 1 MAD Study Key Results (Percent Change from Baseline in Body Weight at Week 12 and Week 13): Cohorta LS Mean (95% CI) at week 12b LS Mean (95% CI) at week 13b All Placebo -0.26 (-1.89, 1.37) -0.25 (-1.88, 1.38) Cohort 3 (weekly dosing) -7.75 (-9.89, -5.61) - Cohort 4 (weekly dosing) -8.70 (-10.75, -6.65) - Cohort 5a (weekly dosing) -9.79 (-11.99, -7.59) - Cohort 5b (every other week dosing) -7.76 (-9.82, -5.70) -9.73 (-11.79, -7.67) Cohort 6 (monthly dosing after week 5) -6.74 (-8.70, -4.79) -7.86 (-9.80, -5.91). ABBV-295 is an investigational, long-acting amylin analog being developed for the treatment of obesity.
It is an agonist that specifically activates amylin and calcitonin receptors. Amylin, a satiety hormone, has been identified as a potential therapeutic target for the treatment of obesity given its role in activating signals to the brain that result in appetite suppression and the reduction of food intake, while also acting as an inhibitory signal to delay gastric emptying. ABBV-295 has not been approved by any health regulatory authority worldwide.
The safety and efficacy of ABBV-295 have not been established. The Phase 1 clinical trial is a two-part, single center, double-blind (within cohorts), randomized, placebo-controlled, single (Part 1) and multiple (Part 2) ascending dose study of subcutaneous ABBV-295 (GUB014295). A total of 76 participants were enrolled in the MAD study.
