A bounded review of sponsor-funded Phase 3 studies in rare genetic obesity syndromes: two small single-arm trials with withdrawal periods and one randomized trial followed by an open-label period.12
Bottom line from this bounded source set
The reviewed studies reported substantial weight reductions in some participants with specific genetic diagnoses. The cohorts were very small, and the Bardet-Biedl and Alström trial reported inconclusive results for the Alström subgroup.12
Reviewed study record
POMC-deficiency obesity trial
Design
A sponsor-funded, single-arm, open-label phase 3 trial included a blinded placebo-withdrawal sequence for participants who first met a weight-loss threshold.1
Population
Ten participants aged at least six years with POMC-deficiency obesity were included in the full analysis and safety sets.1
Outcomes reported
Eight of ten participants achieved at least 10% weight loss at approximately one year. The hunger-score analysis involved a selected subset of seven participants aged at least 12 years who had first met the weight-loss threshold.1
Limitations
The primary one-year endpoint lacked a parallel control group. The small cohort and response-selected withdrawal and hunger analyses limit interpretation and do not establish outcomes in other causes of obesity.1
Reviewed study record
LEPR-deficiency obesity trial
Design
A sponsor-funded, single-arm, open-label phase 3 trial included a blinded placebo-withdrawal sequence for participants who first met a weight-loss threshold.1
Population
Eleven participants aged at least six years with LEPR-deficiency obesity were included in the full analysis and safety sets.1
Outcomes reported
Five of eleven participants achieved at least 10% weight loss at approximately one year. The hunger-score analysis involved a selected subset of seven participants aged at least 12 years who had first met the weight-loss threshold.1
Limitations
The primary one-year endpoint lacked a parallel control group. The small cohort and response-selected withdrawal and hunger analyses limit interpretation and do not establish outcomes in other causes of obesity.1
Reviewed study record
Bardet-Biedl and Alström syndrome trial
Design
A sponsor-funded Phase 3 trial began with a 14-week double-blind randomized placebo-controlled period and continued with a 52-week open-label period.2
Population
The trial randomized 38 participants aged six years or older with obesity and Bardet-Biedl syndrome or Alström syndrome.2
Outcomes reported
After 52 weeks of treatment, 32.3% of participants aged at least 12 years with Bardet-Biedl syndrome reached at least 10% weight reduction; results were reported as inconclusive for Alström syndrome.2
Limitations
The primary endpoint followed the open-label period, the syndrome-specific groups were small, and the reported result should not be generalized beyond the defined genetic populations.2
No registered Crossref update in the reviewed snapshotChecked September 20, 2026 for DOI 10.1016/s2213-8587(20)30364-8. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
Publication update registered by CrossrefErratum ↗ · publisher metadata · February 1, 2023. Crossref metadata identifies the notice but does not by itself explain what wording changed.