The online version of this article (https://doi.org/10.1007/s00198-019-05038-y) contains supplementary material, which is available to authorized users.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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.
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.
European Medicines Agency (2018) Forsteo: EPAR - product information (SmPC). https://www.ema.europa.eu/documents/product-information/forsteo-epar-product-information_en.pdf. Accessed 27 December 2018
Eli Lilly and Company (2013) FORTEO (teriparatide [rDNA origin] injection): Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021318s036lbl.pdf. Accessed 27 December 2018
Blick SK, Dhillon S, Keam SJ (2008) Teriparatide: a review of its use in osteoporosis. Drugs 68(18):2709–2737 CrossRef
Fu Q, Jilka RL, Manolagas SC, O'Brien CA (2002) Parathyroid hormone stimulates receptor activator of NFκB ligand and inhibits osteoprotegerin expression via protein kinase a activation of cAMP-response element-binding protein. J Biol Chem 277(50):48868–48875 CrossRef
Dobnig H, Turner RT (1997) The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats. Endocrinology 138(11):4607–4612 CrossRef
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344(19):1434–1441 CrossRef
Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12-month open-label phases. Bone 47(3):493–502 CrossRef
McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF (2005) Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 165(15):1762–1768 CrossRef
Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, Kaufman JM, Clancy AD, Gaich GA (2003) The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 18(1):9–17 CrossRef
European Medicines Agency and the European Commission (2017) Biosimilars in the EU information guide for healthcare professionals. https://www.ema.europa.eu/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf. Accessed 27 December 2018
Medicines for Europe (2016) Biosimilar medicines handbook. 3rd edn. https://www.medicinesforeurope.com/wp-content/uploads/2016/04/Medicines-for- Europe_BIOSIMILARS_INT_web.pdf#search=%27Biosimilar+medicines+handbook%27. Accessed 22 Nov 2018
European Medicines Agency (2014) Guideline on similar biological medicinal products. CHMP/437/04 Rev 1. https://www.ema.europa.eu/documents/scientific-guideline/guideline-similar-biological-medicinal-products-rev1_en.pdf. Accessed 27 December 2018
US Food and Drug Administration (2015) scientific considerations in demonstrating biosimilarity to a reference product. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf. Accessed 27 December 2018
Ministry of Health, Labour and Welfare, Japan (2009) Guideline for the quality, safety, and efficacy Assurance of Follow-on Biologics. PFSB/ELD Notification No. 0304007. http://www.pmda.go.jp/files/000153851.pdf. Accessed 27 December 2018
European Medicines Agency (2016) Terrosa: EPAR. EMA/833583/2016; EMEA/H/C/003916. https://www.ema.europa.eu/documents/overview/terrosa-epar-summary-public_en.pdf. Accessed 27 December 2018
Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H, Osteoporosis Diagnostic Criteria Review Committee: Japanese Society for Bone and Mineral Research (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19(6):331–337 CrossRef
Orimo H (2015) Japanese 2015 guidelines for prevention and treatment of osteoporosis. Life Science Publishing, Tokyo
ClinicalTrials.gov (2018) A comparison of PF708 and Forteo in osteoporosis patients. https://clinicaltrials.gov/ct2/show/NCT03002428. Accessed 27 December 2018
Yu S, Burge RT, Foster SA, Gelwicks S, Meadows ES (2012) The impact of teriparatide adherence and persistence on fracture outcomes. Osteoporos Int 23(3):1103–1113 CrossRef
Nogues X, Luz Rentero M, Rodriguez AL (2014) Use of an educational support program to assist patients receiving injectable osteoporosis treatment: experience with teriparatide. Curr Med Res Opin 30(2):287–296 CrossRef
Briot K, Ravaud P, Dargent-Molina P, Zylberman M, Liu-Leage S, Roux C (2009) Persistence with teriparatide in postmenopausal osteoporosis; impact of a patient education and follow-up program: the French experience. Osteoporos Int 20(4):625–630 CrossRef
Tamone C, Fonte G, Panico A, Molinatti PA, D'Amelio P, Isaia GC (2012) Impact of a phone follow-up program on persistence with teriparatide or PTH(1-84) treatment. Calcif Tissue Int 90(4):272–278 CrossRef
Tsujimoto M, Uenaka K, Iwata A, Higashiuchi Y, Sowa H (2012) Effects of teriparatide in Japanese and non-Japanese populations: bridging findings on pharmacokinetics and efficacy. J Bone Miner Metab 30(3):326–337 CrossRef
Chen P, Miller PD, Delmas PD, Misurski DA, Krege JH (2006) Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res 21(11):1785–1790 CrossRef
- 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
- Springer London
With other metabolic bone diseases
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
Neu im Fachgebiet Orthopädie und Unfallchirurgie
Mail Icon II