Weekly somapacitan on par with daily growth hormone in children

Weekly somapacitan is noninferior to daily growth hormone (GH) in terms of height velocity (HV), with comparable safety and mean insulin-like growth factor-1 standard deviation score (IGF-1 SDS) levels in treatment-naïve children with growth hormone deficiency (GHD), a study has shown.

“We expect the observed reduction in treatment burden with once-weekly somapacitan will lead to improved adherence and treatment outcomes, while potentially also decreasing the barrier to initiating and/or maintaining replacement therapy,” the researchers said.

To demonstrate the safety and efficacy of somapacitan compared with daily GH, a randomized, multinational, phase III trial was conducted, comprising a 52-week main trial and 3-year extension in 86 sites across 20 countries.

A total of 200 patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (Norditropin; 0.034 mg/kg/d), administered subcutaneously. Annualized HV at week 52 was the primary outcome. The researchers also assessed HV SDS, height SDS, bone age, IGH-1 SDS, patient-reported outcomes, and safety measures.

At week 52, the estimated HV was 11.2 cm/y for somapacitan and 11.7 for daily GH. Noninferiority was achieved. Meanwhile, changes in HV SDS, height SDS, bone age, and IGF-1 SDS from baseline to week 52 were similar between the two groups. Likewise, mean IGH-1 SDS values were comparable between groups and within normal range at week 52 (‒2 to 2). [J Clin Endocrinol Metab 2022;107:3378-3388]

Somapacitan had a safety profile consistent with the daily GH profile. There were low proportions of injection-site reactions reported for both treatment groups (5.3 percent vs 5.9 percent). In addition, both somapacitan and GH similarly reduced disease burden from baseline to week 52, but the former led to a greater treatment burden reduction.

“These results therefore fulfil expectations from medical and research societies for the development of long-acting GH replacement therapies,” the researchers said. [Eur J Endocrinol 2016;174:C1-C8]

Injection-site reactions

GH replacement therapy was approved for GHD treatment in children and was found to improve longitudinal growth with few side effects. [Eur J Endocrinol 2017;177:421-429]

“Despite ongoing improvements in injection device design, daily GH injections can be burdensome for patients and their caregivers, disrupting and interfering with daily life,” the researchers said. “This treatment burden is at least partly responsible for observed nonadherence to prescribed replacement therapy and suboptimal clinical outcomes.” [J Clin Endocrinol Metab 2019;105:e2121-e2133]

Several technologies had been utilized to extend GH action, including GH with noncovalent albumin-binding properties (eg, somapacitan), covalent or transient pegylation (eg, lonapegsomatropin), and as GH-fusion proteins (eg, somatrogon). [J Clin Endocrinol Metab 2019;105:e2121-e2133]

Previous attempts to develop long-acting GHs met a few obstacles, which were commonly associated with injection site reactions. [J Clin Endocrinol Metab 2014;99:126-132; J Clin Endocrinol Metab 2011;96:1718-1726]

On the other hand, earlier studies of somapacitan in both children and adults with GHD have consistently shown rare instances of injection-site reactions (1.8 percent to 6.7 percent of participants), which were mostly mild and transient. [J Clin Endocrinol Metab 2020;105:e1847-e1861; Eur J Endocrinol 2018;178:491-499]

“In line with these findings, few injection site reactions for somapacitan were reported in the current study (5.3 percent), including a very low proportion reporting pain (1.5 percent),” the researchers said.

“Additionally, reported data from this trial indicate that somapacitan in a device of the FlexPro family is easy to learn to use and easy to use and is therefore expected to contribute to an overall positive treatment experience,” they added.

“Together, device-related treatment experience parameters in combination with a low proportion of injection site reactions (including pain) may facilitate patient and caregiver acceptability in addition to the desirable therapeutic profile,” the researchers said.