Biosimilar Teriparatide Matches Forteo in Safety and Fracture Risk

Biosimilar teriparatide is as effective and safe as the reference product (Forteo) for treating osteoporosis, with no significant differences in fracture risk or osteosarcoma incidence, according to a study.¹

As of October 2023, the Ministry of Health in Japan had approved 35 biosimilars, however, biosimilars are still used significantly less than their reference agents. | Image credit: eddows - stock.adobe.com

This study was conducted to address the limited use of biosimilar teriparatide for osteoporosis treatment in Japan due to persistent misconceptions about its safety, efficacy, and quality compared to reference product, despite its potential to reduce health care costs.

“Our findings imply that clinicians need not hesitate to prescribe biosimilar teriparatide for patients with osteoporosis,” wrote the authors.

As of October 2023, the Ministry of Health in Japan had approved 35 biosimilars, however, biosimilars are still used significantly less than their reference agents.² Japan only has 1 teriparatide biosimilar, with Mochida Pharmaceutical’s agent receiving a regulatory decision in September 2019.

By directly comparing the biosimilar's effectiveness (incidence of new fractures) and safety (risk of osteosarcoma) with the reference product, the study, published in the British Journal of Clinical Pharmacology, aimed to provide robust evidence to reassure clinicians, patients, and policymakers, ultimately supporting the adoption of biosimilars and contributing to Japan's goal of increasing biosimilar market share to 80% by 2029.

The researchers retrospective cohort study used the DeSC database, covering approximately 12.5 million individuals in Japan, to analyze the safety of biosimilar teriparatide for osteoporosis. It included patients aged 65 or older diagnosed with osteoporosis who began treatment with either biosimilar teriparatide or its reference product between April 2019 and November 2022. Patients with prior prescriptions for these treatments, malignancies, or conditions increasing fracture risk were excluded.

The study followed patients from their initial prescription to new fracture occurrence, death, deregistration, or study end. The primary outcome was new fractures, while secondary outcomes included osteosarcoma. Covariates such as demographics, comorbidities, and frailty were adjusted using cause-specific Cox proportional hazard models. Sensitivity analyses were conducted to assess the impact of treatment switching, the COVID-19 period, and time-dependent dosing schedules.

After applying inclusion and exclusion criteria, 45,861 patients were included in the study, with 85.4% being female. Patients were categorized into the reference product group (n = 42,248) and the biosimilar group (n = 3,613). Over a median follow-up of 439 days, 6.7% of patients experienced new fractures, and 7.6% died. The biosimilar group had a shorter median follow-up (292 days vs 459 days in the reference group) but showed no significant differences in new fracture incidence (adjusted HR, 0.95; 95% CI, 0.82-1.11; P = .947) or death (P = .979) compared with the reference group. Biosimilar use increased steadily from 1.4% in 2019 to 16.4% in 2022, with similar baseline characteristics between groups.

Regarding osteosarcoma, 4 cases occurred in the reference group and none in the biosimilar group, with no significant difference observed (P = .559). Sensitivity analyses supported the primary results, confirming no significant differences in outcomes between groups.

The authors said their findings regarding incidence of new fractures aligned with those from previous randomized controlled trials testing the reference product. Although the biosimilar's cost is lower, its adoption remained limited, peaking at 16.4% in 2022. If more patients switched to the biosimilar, significant cost savings could be achieved.

Based on a simple calculation, if patients in the present study switched from the reference product to the biosimilar teriparatide for the entire 24-month period, savings of approximately [¥10 trillion or $64,147,500] could be achieved. Therefore, the adoption of the biosimilar teriparatide may also be recommended from a cost perspective,” they wrote.

Limitations included the potential impact of unmeasured confounders and the study population being older than those in prior studies, which may limit generalizability. The low number of osteosarcoma cases also limited statistical power, suggesting the need for further research to better evaluate safety.

References

1. Sato S, Sasabucki T, Okada A, Yasunaga H. Incidence of new fractures in older patients with osteoporosis receiving biosimilar teriparatide or reference products: A retrospective cohort study. Br J Clin Pharmacol. 2025;91(1):143-150. doi:10.1111/bcp.16243

2. Biosimilars approved in Japan. Generics and Biosimilars Initiative. July 3, 2014. Updated October 24, 2023. Accessed January 23, 2025. https://gabionline.net/biosimilars/general/biosimilars-approved-in-japan