Endocrine Abstracts

Objectives: Lonapegsomatropin (SKYTROFA; TransCon hGH), a prodrug of somatropin, is approved by the EMA and FDA for once-weekly treatment of pediatric growth hormone deficiency (GHD). Lonapegsomatropin uses TransCon® technology, which combines a parent drug transiently linked to an inert carrier to achieve sustained release. The characterization of anti-drug antibodies (ADAs) was assessed in 3 phase 3 trials of lonapegsomatropin in pediatric GHD.

Methods: Samples were collected at baseline and at 13-week intervals and analyzed for the presence of ADAs using validated immunoassays. Bridging ELISA, a bridging ECLIA, and an indirect ECLIA assay were set up to assess ADAs against human growth hormone (hGH), lonapegsomatropin (prodrug), and mPEG (carrier), respectively. A cell-based proliferation assay was used to assess the presence of neutralizing anti-hGH antibodies. Analysis of ADAs was performed on samples from 305 participants, with a mean duration of treatment of 3 years (157 weeks (data cutoff date: September 1, 2021)).

Results: No neutralizing antibodies were detected at any time point. At baseline, 1.3% of participants had positive results for anti-hGH antibodies. Treatment-emergent or treatment-boosted anti-hGH antibodies were detected in 5.2% and 0.3% of participants, respectively. Anti-mPEG antibodies at baseline were detected in 2.8% of participants, treatment-emergent anti-mPEG antibodies in 0.7% of participants, and no treatment-boosted anti-mPEG antibodies were detected. Anti-lonapegsomatropin antibodies were detected in 0.4% of participants at baseline, and 4.3% of participants were positive for treatment-emergent anti-lonapegsomatropin antibodies. All antibody titers were low (≤ 400). Antibodies were considered transient, and primarily appeared within 6 months of treatment initiation.

Conclusions: Lonapegsomatropin did not give rise to neutralizing antibodies, and no impact of binding ADAs on efficacy or safety was observed in any of the 305 participants with pediatric GHD. With an average of 3 years of trial participation, these data support the safety of long-term treatment with lonapegsomatropin.