ESPE Abstracts

Objectives: Somatrogon, a long-acting recombinant human growth hormone (GH) consisting of the amino acid sequence of human GH (hGH) and three copies of the carboxy-terminal peptide (CTP) of human chorionic gonadotropin, is approved by the EMA for treatment of children with GH deficiency (GHD). In this phase 3 study, children with GHD received either somatrogon or Genotropin. The impact of testing positive for anti-drug antibodies to somatrogon (ADA+) on the efficacy and safety of somatrogon was evaluated.

Methods: In the 12-month main study, subjects were randomized to once-weekly somatrogon (0.66 mg/kg/week) or once-daily Genotropin (0.24 mg/kg/week). After the main study, subjects could enroll in an open label extension (OLE), where all subjects received somatrogon (0.66 mg/kg/week). Samples to assess ADAs were collected quarterly during the main study and every 6 months during the OLE. Using electrochemiluminescence assays, samples were initially assessed for anti-somatrogon ADAs; ADA+ samples were further assessed for anti-hGH and anti-CTP ADAs. Neutralizing ADAs (NAb) to somatrogon and hGH were identified in assays measuring inhibition of somatrogon/hGH-stimulated cell proliferation. Subjects with ≥1 ADA+ result were compared with subjects with no ADA+ samples (ADA−).

Results: By Month 12, 84/109 (77.1%) somatrogon-treated subjects had ≥1 ADA+ result; most were anti-hGH+. Two of the 84 subjects tested NAb+ for somatrogon. At OLE Month 12, of the 212 subjects (108 subjects had received Genotropin in the main study), 114 (53.8%) had ≥1 ADA+ result; most ADA samples were anti-hGH. No additional subjects tested NAb+ for somatrogon while 3 subjects tested NAb+ for hGH. ADA status had no effect on growth parameters (Table). Being ADA+ was associated with numerically higher mean IGF-1 SDS values and greater changes from baseline but there was considerable overlap between ADA+ and ADA− subjects (Table). The presence of ADAs to somatrogon did not affect the incidence of treatment-emergent adverse events (AEs), serious AEs, or AEs of special interest; there was no association between the incidence of AEs and ADA titer.

Conclusions: ADA+ did not affect the efficacy or safety of somatrogon.

Clinicaltrials.gov:NCT02968004; EudraCT:2016-003874-42