Long-term Safety and Efficacy of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: Results From a 52-Week Open-Label Extension Trial.
Lonapegsomatropin appears to be well tolerated and associated with sustained improvements in body composition and patient-reported outcomes in adults with growth hormone deficiency.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study evaluated the long-term safety and efficacy of once-weekly lonapegsomatropin in adults with growth hormone deficiency over a 52-week open-label extension trial. Participants who completed a prior phase 3 trial received lonapegsomatropin, with safety assessments including adverse events and body composition measurements. Results indicated that the treatment was generally well tolerated with some improvements in body composition and patient-reported outcomes.
Abstract
Objective To evaluate long-term safety and efficacy of once-weekly lonapegsomatropin in adults with growth hormone (GH) deficiency. Methods This 52-week, multicenter, open-label extension trial enrolled adults with GH deficiency who completed the 38-week phase 3 foresiGHt trial, in which participants received lonapegsomatropin, placebo, or somatropin.1 In the extension, all participants received lonapegsomatropin. Safety assessment included adverse events (AEs), laboratory values, vital signs, immunogenicity, 12-lead electrocardiograms, and fundoscopy. Body composition (trunk percent fat, trunk fat mass, visceral adipose tissue, total body lean mass, trunk lean mass, and appendicular lean mass) was measured by dual-energy X-ray absorptiometry, and patient-reported outcomes were evaluated. Results Following foresiGHt completion, 220 (88.7%) participants enrolled in the extension. Across foresiGHt and the extension, common lonapegsomatropin-associated AEs were nasopharyngitis, upper respiratory infection, and headache. Injection site reactions were infrequent (5.1%) and mild or moderate. After up to 90 weeks of treatment, body composition was maintained in participants continuing lonapegsomatropin, and improved relative to foresiGHt baseline in those initiating or switching to lonapegsomatropin. Clinically meaningful improvements in patient-reported outcomes from foresiGHt baseline were observed; 43.5%, 40.6%, and 35.8% of participants achieving a ≥10-point improvement in Treatment Related Impact Measure-Adult GH Deficiency (TRIM-AGHD) total score among those continuing, initiating, or switching to lonapegsomatropin, respectively. Conclusions Once-weekly lonapegsomatropin was generally well tolerated and was associated with sustained improvements in body composition and patient-reported outcomes for up to 90 weeks. These findings extend prior evidence and support the long-term benefits of lonapegsomatropin in adults with GH deficiency, including those switching from somatropin.
Background
This paper addresses the long-term safety and efficacy of lonapegsomatropin in adults with growth hormone deficiency, building on prior phase 3 trial findings. Previous studies have indicated potential benefits of growth hormone therapy, but long-term data remain limited. Understanding the sustained effects and safety profile of lonapegsomatropin is crucial for informed clinical practice.
Methods
The study was a 52-week, multicenter, open-label extension trial involving adults with growth hormone deficiency who completed a prior 38-week phase 3 trial. All participants received lonapegsomatropin during the extension. Primary outcome measures included safety assessments and body composition changes, with secondary measures focusing on patient-reported outcomes.
Results
Following the completion of the foresiGHt trial, 220 participants (88.7%) enrolled in the extension. Common adverse events included nasopharyngitis and upper respiratory infection. Injection site reactions occurred in 5.1% of participants, classified as mild or moderate. Improvements in body composition were noted, with 43.5%, 40.6%, and 35.8% of participants achieving a ≥10-point improvement in TRIM-AGHD total score.
Interpretation
The findings suggest that lonapegsomatropin may provide sustained improvements in body composition and patient-reported outcomes, consistent with prior literature. However, the clinical significance of the observed improvements, particularly the percentage of participants achieving a ≥10-point improvement in TRIM-AGHD, should be interpreted cautiously given the open-label design and potential for bias. The study's limitations, including the lack of a control group and the absence of long-term follow-up data beyond 90 weeks, further constrain the conclusions.
Key findings
- 220 (88.7%) participants enrolled in the extension.
- 5.1% experienced injection site reactions, which were mild or moderate.
- 43.5%, 40.6%, and 35.8% of participants achieved a ≥10-point improvement in TRIM-AGHD total score among those continuing, initiating, or switching to lonapegsomatropin, respectively.
Limitations
- open-label design may introduce bias
- long-term effects beyond 90 weeks not reported
- no control group in the extension trial