ESPE Abstracts (2015) 84 P-2-415

The Pharmacokinetics and Pharmacodynamics of TV-1106, a Once Weekly GH Supplement: Results from a Phase 2 Study of TV-1106 in Adults with GH Deficiency

Orit Cohen-Baraka, Jens Sendahl Christiansenb, Martin Bidlingmaierc, Kurt Brownd, Anat Sakove, Gaya Anscheutzf & Kathleen Butlerd

aPharmacokinetics and Phase 1 Studies Teva Pharmaceuticals, Netanya, Israel; bDepartment of Endocrinology, MEA, Aarhus University Hospital NBG, Aarbus, Denmark; cMedizinische Klinik und Poliklinik IV, Ludwig-Maximilian-University of Munich, Munich, Germany; dClinical Development Teva Pharmaceuticals Ltd, Frazer, PA, USA; eBiostatistics Teva Pharmaceuticals Ltd, Netanya, Israel; fBiostatistics Teva Pharmaceuticals Ltd, West Chester, PA, USA

Background: TV-1106 (Teva Pharmaceuticals Ltd) is a genetically fused recombinant GH (rhGH) and human serum albumin in development as a once weekly treatment of GH deficiency (GHD) in children and adults. TV-1106 has an extended duration of action compared to daily rhGH treatment, reducing the frequency of injections.

Objective and hypotheses: The pharmacokinetics and pharmacodynamics of TV-1106 were evaluated in phase 2 study using non-compartmental analysis (NCA) performed on serum concentrations of adults with GHD during week 12 of TV-1106 treatment.

Method: Patients with GHD (N=93) on stable rhGH treatment and having a normal IGF1 level (−1.5 to +2.0 SDS) participated in screening; to be eligible for randomization, they had to demonstrate reduction of at least 1 IGF1 SDS from screening during a 4 weeks washout period and IGF1 SDS <0 post washout. Of 41 patients randomized to TV-1106, 31 were included in pharmacokinetic analyses and were divided into one of four TV-1106 dose quartiles (3.36–<8.96 mg, ≧8.96–<12.32 mg, ≧12.32–<15.12 mg and ≧15.12–≤31.92 mg). 11 patients received daily injections of Genotropin as an active control.

Results: There was a wide variability in plasma concentrations of TV-1106 with the highest overall exposure based on Cmax and AUC0-t observed for highest dose quartile and substantially less exposure for three lower dose quartiles. Overall pharmacodynamic effect of TV-1106 on IGF1 levels followed a similar pattern with mean IGF1 Cmax values highest for highest dose quartile and lowest for lowest dose quartile. Mean Cmax, the maximum levels of Cmax in SD score (SDS) units, and median Tmax IGF1 values were similar between the TV-1106 and Genotropin groups.

Conclusion: Adult patients with GHD, previously stable with daily rhGH treatment, when given weekly TV-1106 administration show IGF1 levels comparable to Genotropin.

Funding: This work is supported by the Research and Development Division of Teva Pharmaceuticals Ltd. Israel.

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