AbbVie announced topline results from the multiple ascending dose portion of a Phase I study of ABBV-295, a long-acting amylin analog, in adults. The subcutaneous agent produced dose-dependent body weight reductions of up to 9.79% over 12 to 13 weeks, positioning AbbVie as a late entrant in the obesity space with a non-incretin mechanism.
Trial specifics
The GUC17-01 study is a two-part, single-center, double-blind, randomized, placebo-controlled trial evaluating subcutaneous ABBV-295 in adults with a mean BMI below 30 kg/m². The MAD portion enrolled 76 participants, of whom 88.3% were male. Doses ranged from 2 mg to 14 mg across multiple cohorts testing weekly, every-other-week, and monthly (after week 5) administration schedules. The study’s formal primary endpoints were safety, tolerability, pharmacokinetics, and pharmacodynamics, with body weight change from baseline measured as an efficacy readout using a mixed model for repeated measures.
In weekly dosing cohorts, least-squares mean percentage body weight change at week 12 ranged from -7.75% to -9.79%. The every-other-week cohort reached -9.73% at week 13, while the monthly dosing group achieved -7.86% at the same timepoint. Placebo arms recorded -0.26% and -0.25% at weeks 12 and 13, respectively. ABBV-295 was generally well tolerated; the most common adverse events were mild gastrointestinal disorders concentrated in the first six weeks. No serious adverse events were reported.
AbbVie said full data will be presented at a future scientific conference while Primal Kaur, AbbVie’s senior vice president of global development, stated that the results “reinforce the potential of ABBV-295 as a novel therapeutic option for people living with obesity”, although no specific timelines for next phase development have been disclosed.
AbbVie originally acquired the molecule, designated GUB014295, from Denmark-based Gubra ApS, which had previously reported results from the single ascending dose part and earlier MAD cohorts.
Research context
ABBV-295 is an agonist that activates both amylin and calcitonin receptors. Amylin is a satiety hormone co-secreted with insulin from pancreatic beta cells. Its central nervous system signaling suppresses appetite, reduces food intake, and delays gastric emptying. This pathway is mechanistically distinct from the incretin-based approaches — GLP-1 and GIP receptor agonism — that dominate the current obesity treatment landscape. Pramlintide, a first-generation amylin analog approved for diabetes, showed modest weight effects but required thrice-daily dosing. ABBV-295’s long-acting profile, enabling weekly to monthly administration, addresses that limitation.
The obesity drug market is dominated by the two leading incretin therapies, Novo Nordisk’s semaglutide (Wegovy) and Eli Lilly’s tirzepatide (Zepbound). Behind them, several next-generation candidates are in late-stage development. Amylin-based approaches have attracted particular attention as a complementary or alternative mechanism, with multiple companies pursuing this target class. Key competitors include:
Amylin-based therapies
- cagrilintide (Novo Nordisk) — long-acting amylin analog in Phase III REDEFINE trials with semaglutide.
- petrelintide (Zealand Pharma/Roche) — long-acting amylin analog in Phase II development.
Combination incretin competitors
- retatrutide (Eli Lilly) — GLP-1/GIP/glucagon triple agonist in Phase III.
- MariTide (Amgen) — GLP-1 agonist/GIP antagonist in Phase II.
- danuglipron (Pfizer) — oral GLP-1 receptor agonist in Phase II.
- amycretin (Novo Nordisk) — dual GLP-1/amylin agonist approaching Phase III.
The weight reductions observed with ABBV-295 in a population with mean BMI below 30 — not the typical obesity trial population — complicate direct comparison with these competitors. Phase I data in leaner individuals may overstate or understate effects relative to later trials in people with obesity. Still, the magnitude of weight loss at this stage, combined with the tolerability profile and dosing flexibility, provides a rationale for continued development. Whether AbbVie pursues ABBV-295 as monotherapy or positions it for combination with incretin agents remains undisclosed.