Teriparatide(The Chemical Works of Gedeon Richter Plc)

In January 2017, the European Commission approved Terrosa^® (company code RGB-10) as one of the first biosimilar medicinal products of teriparatide for the same indications as for the reference medicinal product Forsteo^® (Lilly France S.A.S.), which has been on the market in the European Union since 2003. The active pharmaceutical ingredient of the reference medicinal product is the biologically active 1-34 fragment of the endogenous human parathyroid hormone [PTH(1-34)]. It is one of the three bone anabolic agents used in the treatment of osteoporosis promoting bone formation and preventing fragility fractures.

The objective of this paper is to summarise the results of the comparative analysis of representative batches of both the RGB-10 drug product and the reference medicinal product performed by physicochemical and in vitro biological methods.

A series of state-of-the-art analytical methods were applied in a comparative head-to-head manner for testing the similarity in respect to purity, content, structure and potency.

Based on the results of the comprehensive physicochemical and biological characterisation, RGB-10 proved to be highly similar to the reference medicinal product with respect to the critical quality attributes investigated.

The results of the quality comparability study demonstrated similarity of RGB-10 to the reference medicinal product, providing the scientific basis for conducting a specifically designed clinical programme, and supported registration of the Marketing Authorisation Application of RGB-10 in the EU.

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.

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.

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.

The therapeutic equivalence of RGB-10 to reference teriparatide was demonstrated. RGB-10 had comparable safety profile to that of reference teriparatide.