Pharmacokinetics similarities were found between BP02 (CuraTeQ Biologics), a proposed biosimilar to trastuzumab (Herceptin; Genentech), and the reference product in both the European Union and the United States, according to a study published in Oncology and Therapy. Furthermore, the results showed that the 3 products had safety and immunogenicity consistent with previous reports for the reference product.1
Trastuzumab was the first monoclonal antibody approved by the FDA that targets human epidermal growth factor receptor 2 (HER2). It is approved for adjuvant breast cancer, metastatic breast cancer, and gastric cancer expressing HER2. The authors stated that there are barriers to access for trastuzumab, including high costs in low-to-middle-income countries and for patients with advanced or metastatic breast cancers. In April 2024, the FDA approved a biosimilar for trastuzumab, Hercessi (Accord BioPharma Inc), which demonstrated similarities in safety, efficacy, and quality between the biosimilar and the reference product.1,2
BP02 binds to the extracellular domain of HER2 receptors, like both the EU and US formulations. Investigators of the study aimed to determine the equivalence of the proposed biosimilar to the reference products, including pharmacokinetics, safety, and immunogenicity.1
The study was a phase 1 randomized, double-blind trial conducted in New Zealand between July 2021 and May 2023, and was restricted to healthy male volunteers aged 28 to 65. Healthy individuals were used in order to control the variability, according to the study authors. Treatment was randomized 1:1:1, with individuals receiving their respective treatments in a 6 mg/kg dosage as an intravenous infusion over 90 minutes.1
Blood samples were collected pre-infusion, then at 0.5, 1, 4, and 6 hours after infusion. Furthermore, samples were taken 25 hours and 45 hours post-dose relative to the start of infusion as well as on days 3, 4, 15, 22, 29, 36, 50, 64, and 78. The primary end point was the area under the serum concentration–time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from time of dosing until time of last quantifiable concentration (AUC0-t), and peak serum concentration for the drug (Cmax). Furthermore, secondary end points included time to achieve Cmax, half-life, elimination rate constant, and systemic clearance of trastuzumab, according to the study authors. The safety evaluations were also performed for each drug.1
Key Takeaways
- Trastuzumab, a drug for HER2-positive cancers, can be cost-prohibitive in some regions. BP02 is a proposed biosimilar aiming to increase access and potentially reduce costs.
- A phase 1 study showed that BP02 has a similar pharmacokinetic profile (drug movement in the body) compared to both the EU and US formulations of trastuzumab. This suggests similar effectiveness.
- The study found that BP02 was well-tolerated with a safety profile comparable to the reference products. Most side effects were mild to moderate.
In the study, 111 total individuals received treatment with 37 in each group, according to the authors. A total of 106 completed the study with 1 withdrawing from the study drug group and 4 withdrawing from the US formulation group. Of 104 individuals included in the pharmacokinetics analysis, investigators found that the serum concentration–time was similar for all 3 groups as well as the primary end points and the secondary endpoints.1
For the 111 individuals, there were 281 treatment-related adverse events (TRAEs) reported, with most being either mild or moderate in severity. There were 89.2% reported in the US group and 73% each in the biosimilar and EU groups. Further, for those who reported moderate TRAEs, the US group reported higher proportions at 29.7% compared with 10.8% and 13.5%, respectively. Four individuals discontinued the study due to TRAEs with 1 in the biosimilar group and 3 in the US group.1
References
1. Schwabe C, Wynne C, Dyapa DR, Prajapati A, Dadke D. Pharmacokinetics, Safety, Tolerability, and Immunogenicity of BP02 (Trastuzumab Biosimilar) Compared to EU- and US-Approved Trastuzumab in Healthy Adult Male Volunteers: A Phase 1, Randomized, Double-Blind Study. Oncol Ther. Published online July 7, 2024. doi:10.1007/s40487-024-00289-0
2. Ferruggia K. FDA approves trastuzumab biosimilar to treat forms of HER2-overexpressing cancer. Pharmacy Times. April 29, 2024. Accessed July 24, 2024. https://www.pharmacytimes.com/view/fda-approves-trastuzumab-biosimilar-to-treat-forms-of-her2-overexpressing-cancer
