ESPE Abstracts (2016) 86 P-P1-603

ESPE2016 Poster Presentations Growth P1 (48 abstracts)

Pediatric Phase 2 Data Demonstrate that TransCon hGH Has an Anti-hGH Immunogenic Profile that is Comparable to Daily hGH

David Gilfoyle a , Susanne Pihl a , Pierre Chatelain b & Michael Beckert a

aAscendis Pharma A/S, Hellerup, Denmark; bDivision of Endocrinologie Pediatrique – Hopital Mere-Enfant, University Claude Bernard Lyon1, Lyon, France

Background: TransCon hGH, is a once-weekly prodrug releasing unmodified hGH, for the treatment of Growth Hormone Deficiency (GHD) in children and adults. To date, TransCon hGH has demonstrated comparable efficacy, safety and anti-hGH immunogenic profile to daily hGH, with no occurrence of neutralizing antibodies.

Objective and hypotheses: Protein-based therapies may be associated with generation of drug-specific antibodies, which may impact efficacy, particularly if they neutralize the activity of the protein. Patients with neutralizing anti-hGH antibodies may not respond to hGH therapy, and may require initiation of IGF-I therapy to facilitate growth. As daily hGH therapy utilizes the recombinant human protein, the immunogenic potential is low. Sensitive anti-hGH binding and neutralizing antibody assays have been developed, validated and utilized to assess anti-hGH immunogenicity in a Phase 2 clinical study of children with GHD.

Method: Pre-pubertal, treatment-naïve, children with GHD (n=53) were randomized to weekly S.C. injections of TransCon hGH at 0.14, 0.21 and 0.30 mg hGH/kg per week or daily S.C. injections of Genotropin at 0.21 mg hGH/kg per week for 26 weeks. Serum samples were collected during screening, pre-dose Weeks 1, 5 and 13 and following the last dose at Week 26. Samples were assessed for anti-hGH binding and, if appropriate, neutralizing antibodies. Anti-hGH binding and neutralizing antibodies were detected in serum using validated bridging ELISA and cell-based proliferation assays, respectively.

Results: Very low levels of treatment-emergent anti-hGH immune response was detected in 1 subject (2.5%), which were confirmed to be non-neutralizing (0.14 mg hGH/kg per week TransCon hGH). There was no impact on the subject’s pharmacokinetic (TransCon hGH and hGH) or pharmacodynamic (IGF-I) profiles and the subject demonstrated an annualized height velocity of 19.0 cm.

Conclusion: Sustained-release TransCon hGH is considered to have an anti-hGH immunogenic profile comparable to that of daily hGH and maintain the same safe and efficacious hGH levels in the body as currently available daily therapies.

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