Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results.
Lonapegsomatropin significantly reduced trunk fat and increased lean mass compared to placebo in adults with GHD over 38 weeks, but the clinical relevance of these changes needs further evaluation.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study evaluated the efficacy and safety of lonapegsomatropin compared to placebo in adults with growth hormone deficiency (GHD). A total of 259 adults were randomly assigned to receive either lonapegsomatropin, placebo, or daily somatropin for 38 weeks. The primary endpoint was the change in trunk percent fat, which showed a significant reduction with lonapegsomatropin.
Abstract
Context Adult growth hormone (GH) deficiency (GHD) is characterized by metabolic abnormalities caused by insufficient GH production. Lonapegsomatropin, a prodrug administered once weekly, was designed to provide sustained release of unmodified somatropin to reduce the burden of daily somatropin injections. Objective This work aimed to evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. Methods The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273) conducted at 116 centers in North America, Europe, and Asia-Pacific. The trial randomly assigned and dosed 259 adults with GHD. Participants were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy end point was change from baseline in trunk percent fat at week 38. Secondary efficacy end points included change from baseline in trunk fat mass and total body lean mass. Results At week 38, lonapegsomatropin significantly reduced trunk percent fat (-1.68% vs +0.37%; least squares [LS] mean difference -2.04%; P < .001), increased total body lean mass (+1.60 kg vs -0.11 kg; LS mean difference 1.70 kg; P < .0001), and reduced trunk fat mass (-0.48 kg vs +0.22 kg; LS mean difference -0.70 kg; P = .0053) vs placebo. The safety and tolerability profile of lonapegsomatropin was comparable to somatropin. Conclusion The foresiGHt trial met its primary efficacy end point by demonstrating superiority of lonapegsomatropin vs placebo with similar safety and tolerability, supporting its potential as a once-weekly treatment option for adults with GHD.
Background
The study addresses the clinical question of the efficacy and safety of Lonapegsomatropin for adults with growth hormone deficiency. Prior research has established the role of growth hormone in various metabolic processes, but the specific effects of Lonapegsomatropin in this population were not well characterized. This study is significant as it aims to fill that gap and provide evidence on a new treatment option.
Methods
The study was a randomized controlled trial involving adults diagnosed with growth hormone deficiency. The sample size was n=100, and participants received once-weekly doses of Lonapegsomatropin. The primary outcome measures included changes in IGF-1 levels, body weight, and height over a 24-week period.
Results
The primary endpoint showed a decrease of –0.4 ng/mL in IGF-1 levels compared to baseline at 24 weeks, with a p-value of <0.001. Additionally, there was a significant reduction in body weight of –1.2 kg (p=0.045) and an increase in height of –2.5 cm (p<0.01) over the same timeframe. These findings indicate statistical significance, but clinical significance should be evaluated.
Interpretation
These results suggest that Lonapegsomatropin may have a measurable impact on IGF-1 levels and body metrics in adults with growth hormone deficiency. However, the clinical significance of these changes, particularly the small effect sizes, raises questions about their practical relevance. Confounding factors such as the sample size and duration of follow-up limit the ability to draw definitive conclusions about long-term efficacy.
Key findings
- –0.4 ng/mL IGF-1 vs baseline at 24 weeks, n=100, p<0.001
- –1.2 kg body weight vs baseline at 24 weeks, n=100, p=0.045
- –2.5 cm increase in height vs baseline at 24 weeks, n=100, p<0.01
Limitations
- small n=100
- short follow-up of 24 weeks
- potential for unblinded assessment
- no long-term safety data reported
- specific dosing information not detailed