ESPE Abstracts

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 C_max and AUC_0-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 C_max values highest for highest dose quartile and lowest for lowest dose quartile. Mean C_max, the maximum levels of C_max in SD score (SDS) units, and median T_max 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.