Growth hormone deficiency (GHD) in adults, a rare disorder characterized by decreased or absent endogenous growth hormone production, leads to abnormal body composition, dyslipidemia, insulin resistance, and increased risks of metabolic syndrome, cardiovascular disease, and impaired quality of life, including cognitive and psychological issues. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in managing related comorbidities, but adherence to the standard daily somatropin injections remains a challenge. Ascendis Pharma A/S has developed SKYTROFA® (lonapegsomatropin-tcgd), a prodrug of somatropin administered weekly, previously approved by the U.S. Food & Drug Administration (FDA) in 2021 for pediatric GHD. This study evaluates its efficacy and safety for adult GHD.
The FDA approval for adult GHD was supported by the foresiGHt Phase 3 trial, a randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) study. The trial compared weekly TransCon hGH (lonapegsomatropin) with weekly placebo and daily somatropin in adults with GHD, assessing efficacy endpoints such as growth hormone levels, body composition, and quality of life, alongside safety profiles.
The trial demonstrated that SKYTROFA effectively replaced growth hormone with a favorable safety profile, offering sustained release of unmodified somatropin. Compared to daily injections, the once-weekly regimen reduced the treatment burden, potentially improving adherence. Common adverse events included fluid retention and low thyroid hormone levels, manageable with monitoring. The approval marks a significant advancement, with market research indicating strong preference among patients and physicians for SKYTROFA in pediatric GHD, now extended to adults initiating or switching therapies.
The FDA approval of SKYTROFA for adult GHD represents a milestone in endocrine therapy, providing a less burdensome, effective alternative to daily somatropin. Its sustained-release mechanism and potential to enhance adherence could improve long-term outcomes for adults with GHD. Ascendis Pharma aims to expand SKYTROFA’s indications, reinforcing its position as a leader in rare endocrinology diseases. Further studies are warranted to optimize its use and monitor long-term safety.
