Poster Presentation ESA-SRB-APEG-NZSE 2022

Efficacy and safety of once-weekly somatrogon in pediatric subjects with growth hormone deficiency: lack of impact of anti-drug antibodies (#447)

Cheri L Deal 1 , Lawrence A Silverman 2 , Joan Korth-Bradley 3 , Carl L Roland 4 , Carrie T Taylor 5 , Jose F Cara 5 , Michael P Wajnrajch 5 6 , Roy Gomez 7
  1. Centre de recherche CHU Ste-Justine, Université de Montréal, Montréal, Canada
  2. Goryeb Children’s Hospital, Morristown, NJ, USA
  3. Pfizer Inc, Collegeville, PA, USA
  4. Pfizer Inc, Sanford, NC, USA
  5. Pfizer Inc, New York, NY, USA
  6. New York University Grossman School of Medicine, New York, NY, USA
  7. Pfizer Pte Ltd, Singapore

Somatrogon, a long-acting recombinant human growth hormone (GH) is approved in several countries as a once-weekly treatment for children with GH deficiency (GHD). In this phase 3 study, children with GHD received somatrogon or Genotropin. We evaluated the impact of testing positive for anti-drug antibodies to somatrogon (ADA+) on the efficacy and safety of somatrogon.

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. 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 also identified. Subjects with ≥1 ADA+ result were compared with subjects with no ADA+ samples (ADA−).

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.

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

Clinicaltrials.gov:NCT02968004

62fe26f806ecd-ADA_impact_APEG22_TABLE.PNG