ESPEYB20 2. Growth and Growth Factors Long-Acting Growth Hormone (LAGH) (5 abstracts)
2.9. Safety and efficacy of lonapegsomatropin in children with growth hormone deficiency: enliGHten trial 2-year results
Maniatis AK , Casella SJ , Nadgir UM , Hofman PL , Saenger P , Chertock ED , Aghajanova EM , Korpal-Szczyrska M , Vlachopapadopoulou E , Malievskiy O , Chaychenko T , Cappa M , Song W , Mao M , Mygind PH , Smith AR , Chessler SD , Komirenko AS , Beckert M , Shu AD & Thornton PS
J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2680–e2689. doi: 10.1210/clinem/dgac217. PMID: 35428884; PMCID: PMC9202697
Brief summary: This open-label extension trial enrolled all subjects completing the two previous phase 3 Lonapegsomatropin trials, heiGHt and fliGHt. The results confirm the efficacy of this LAGH formulation in improving height SDS, without major adverse events.
Lonapegsomatropin is a long-acting GH consisting of 3 components: unmodified human GH (hGH), an inert glycol carrier, and a TransCon linker that transiently binds the other 2 components. The glycol carrier extends hGH circulation time in the body by shielding GH receptor binding and renal excretion. The TransCon linker releases hGH by autocleavage in a controlled manner.
This study reports the results from EnliGHten, an open-label extension trial that aimed at assessing the long-term safety of weekly Lonapegsomatropin (0.24 mg/kg/week) in children with GHD previously treated in the phase 3 Lonapegsomatropin trials heiGHt or fliGHt (1, 2). Almost all subjects who completed the heiGHt (158/159) and fliGHt (140/144) trials continued into the EnliGHten long-term extension trial for up to 2 years. Efficacy assessments included the endpoints of height SDS and annualized height velocity (AHV).
In subjects from heiGHt trial, height SDS improved from −2.9 at heiGHt trial baseline to −1.4 at week 104 (=2 yrs). The mean AHV was 10.9 cm/year at week 52 and 8.5 cm/year at week 104.
Subjects who were on daily somatropin during the heiGHt trial and switched to Lonapegsomatropin also improved their height SDS from −3.0 at heiGHt trial baseline to −1.5 at week 104; their mean AHV was 10.2 cm/year at week 52 and 8.9 cm/year at week 104.
In subjects from fliGHt trial, height SDS improved from −1.4 at baseline to −0.7 and mean AHV was 8.4 cm/year at week 78. There was no advancement in bone age in children receiving Lonapegsomatropin, indicating that the clinical effects did not occur at the expense of skeletal maturation.
Mean IGF-1 SDS remained stable for heiGHt subjects already on Lonapegsomatropin, whereas in those who were initially on daily GH an initial increase in mean IGF-1 SDS with subsequent stabilization was observed. For fliGHt subjects, mean IGF-1 SDS increased from 0.8 at fliGHt baseline to 1.6 at week 26 and 1.8 at week 78.
As observed in the heiGHt and fliGHt trials, AEs were generally mild and consistent with those reported in other clinical trials evaluating daily GH children with GHD. Blood parameters remained stable and no serious AEs related to Lonapegsomatropin were reported.
In conclusion, weekly Lonapegsomatropin produced a continued improvement of height SDS through 2 years of therapy without advancing bone age. The safety and tolerability profile of Lonapegsomatropin remained comparable to daily GH.
References: 1. Thornton PS, Maniatis AK, Aghajanova E, et al. Weekly lonapegsomatropin in treatment-naive children with growth hormone deficiency: the Phase 3 heiGHt trial. J Clin Endocrinol Metab. 2021;106(11):3184–3195. 2. Maniatis AK, Nadgir U, Saenger P, Reifschneider KL, Abuzzahab J, Deeb L, Fox LA, Woods KA, Song W, Mao M, Chessler SD, Komirenko AS, Shu AD, Casella SJ, Thornton PS. Switching to weekly lonapegsomatropin from daily somatropin in children with growth hormone deficiency: the fliGHt trial. Horm Res Paediatr. 2022;95(3):233–243. doi: 10.1159/000524003. Epub 2022 Mar 9. PMID: 35263755; PMCID: PMC9501775.
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ESPE Yearbook of Paediatric Endocrinology
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