Clinical comparison of efficacy and safety of two teriparatide formulations: Osteofortil® and forteo®

Teriparatide is an analogue of human parathyroid hormone, used to treat osteoporosis. To develop Osteofortil® (Biosidus S.A., Buenos Aires, Argentina) a new pharmaceutical product containing teriparatide, EMA guidelines for the development of medications were used. We report preliminary data corresponding to the comparison on efficacy and tolerability with the reference teriparatide product (Forteo®, Eli-Lilly, Indianapolis, IN, USA). Materials and methods: Randomized simple blind trial was designed in a single osteoporosis reference center. Teriparatide dose was 20 μg day by subcutaneous injection. Inclusion criteria: posmenopausal women between 50 and 81 years, with osteoporosis defined by mineral bone density (MBD) on lumbar spine (LS) < -2.5 (Tscore) or lumbar fracture with MBD <-2 on LS, femoral neck or total hip. The IRB, an ethical committee and the national drug regulatory agency of Argentina (ANMAT) approved the trial, also registered in clinicaltrials. gov (NCT 01945788). A comparative six-month initial phase was followed by an extension in which all patients were invited to receive Osteofortil® for 6 months. Data were analyzed using simple calculation, Mann Whitney U tests. Data were analyzed using the STATA 12 package (Stata Corp). A total of 182 patients were enrolled and 100 met inclusion and exclusion criteria, 95 and 72 completed the comparative and the extension phase, respectively. Osteocalcin levels (O), N-terminal propeptide of procollagen type 1 (P1NP), C-terminal cross-linked telopeptide of type I collagen (CTX) were measured by Roche E411 ECLIA Electrochemi-luminescence, at baseline and months 1, 3, 6, 9 and 12. BMD was assessed after 6 and 12 months of treatment with DEXA (dual-energy x-ray absorptiometry) by Lunar Prodigy ™, GE Healthcare, Madison, WI, USA. The induction of anti-teriparatide antibodies was evaluated by ELISA. Results The mean age was 65.6 years, with no differences in age at menopause, previous use of bisphosphonates, vitamin D and the presence of fractures at baseline between both groups. At 6 months n = 48 Osteofortil® increased O levels 60.3 ± 30 mg/ml, P1NP 146.8 ± 98 mg/ml CTX 816.2 ± 467 pg/ml, whereas corresponding figures for Forteo were 67.8 ± 29.4 mg/ml, 179 ± 97 mg/ml and 1046 ± 656 pg/ml, (p 0.46, 0.56, 0.45) respectively. At 12 months the Ostefortil® values were O= 66.9 ± 36 mg/ml, CTX 727 ± 322 pg/ml P1NP 155 ± 100 mg/ml, vs Forteo® values of 62.6 ± 35.9 mg/ml, 786 ± 459 pg/ml and 166 ± 109 mg/ml, respectively. No differences between groups were found. The increase in mineral density in CL at 6 months was 5.46% with Forteo® and 5.43% with Osteofortil® (p 0.22). There was no induction of anti-PTH antibody with any product. Adverse events were similar between groups. Conclusions: Both products resulted in similar increase in bone markers and mineral bone density in the lumbar spine. Both depicted similar safety.