A multicenter, randomized, rater-blinded, parallel-group, phase 3 study to compare the efficacy, safety, and immunogenicity of biosimilar RGB-10 and reference once-daily teriparatide in patients with osteoporosis.

The efficacy and safety of RGB-10 and reference teriparatide were evaluated in a randomized 52-week study in 250 patients with osteoporosis at high risk of fracture. RGB-10 was equivalent to reference teriparatide in efficacy and had a comparable safety profile. INTRODUCTION: RGB-10 is the first biosimilar teriparatide authorized in the European Union. This multicenter, randomized, rater-blinded, parallel-group phase 3 study evaluated equivalence in efficacy and compared safety between RGB-10 and reference teriparatide in patients with osteoporosis at high risk of fracture for registration in Japan. METHODS: Ambulatory postmenopausal women and men (≥ 55 years of age) with osteoporosis at high risk of fracture were randomized 1:1 to receive either RGB-10 or reference teriparatide 20 µg once daily via subcutaneous self-injection for 52 weeks. The primary efficacy endpoint was the percent change from baseline to 52 weeks in lumbar spine (L2-L4) bone mineral density (BMD). Safety outcomes and immunogenicity were also assessed. RESULTS: In total, 250 patients (125 in each group) were randomized. The percent change from baseline to 52 weeks in lumbar spine (L2-L4) BMD (mean ± standard deviation) was 8.94% ± 6.19% in the RGB-10 group and 9.65% ± 6.22% in the reference teriparatide group. The estimated between-group difference (95% confidence interval) was - 0.65% (- 2.17% to - 0.87%) within the pre-specified equivalence margin (± 2.8%), which indicates equivalence in efficacy between the two groups. Changes in BMD at lumbar spine (L1-L4), femoral neck, and total hip and serum procollagen type I amino-terminal propeptide were also similar between the groups. Safety profiles, including immunogenicity, were comparable. CONCLUSIONS: The therapeutic equivalence of RGB-10 to reference teriparatide was demonstrated. RGB-10 had comparable safety profile to that of reference teriparatide.

New insights into interactions between the human PTH/PTHrP receptor and agonist/antagonist binding.

We prepared a polyclonal antiserum [Ab-(88-97)] against residues 8-97 of the NH2-terminal tail of the human (h) parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor. Ab-(88-97) bound specifically to the receptor, as assessed by fluorescence-activated cell sorter analysis of HEK C21 cells, which stably express approximately 400,000 hPTH/PTHrP receptors per cell. Unlike PTH, Ab-(88-97) binding did not elicit either adenosine 3',5'-cyclic monophosphate or intracellular calcium concentration signaling responses in these cells. Incubation of C21 cells for 90 min at 4 degrees C with hPTH-(1-34) plus antiserum reduced the Ab-(88-97) binding to the cells by up to 40-50% of control values in a PTH concentration-dependent fashion with a half-maximal effective concentration of approximately 5 nM. The decrease in Ab-(88-97) binding caused by hPTH-(1-34) was completely reversed by coincubation with hPTHrP-(7-34). We conclude that residues 88-97 of the hPTH/PTHrPR are involved, either directly or indirectly, in agonist but not antagonist binding to the receptor.

Antibody against synthetic rat PTH peptide (1-34) blocks PTH-mediated cAMP formation and phosphate transport in opossum kidney cells.

A novel antibody against synthetic rat parathyroid hormone (rPTH(1-34)) was successfully produced in rabbits at a titer of 1:3,000. The ability of this antibody to block PTH was studied utilizing the hormone-sensitive cAMP formation and Na(+)-dependent phosphate transport in the opossum kidney (OK) cells. rPTH peptide(1-34) stimulated cAMP formation and inhibited Na(+)-dependent phosphate transport in OK cells in a dose-dependent manner. Treatment of OK cells with the antisera significantly decreased the level of cAMP and attenuated the inhibition of Na(+)-dependent phosphate transport in response to rPTH(1-34) at a dilution of 1:1,000. Nonimmune rabbit sera at the same dilution did not influence these hormone-sensitive effects. We conclude that antibody against synthetic PTH peptide can be used to study the biological activities of this hormone.