Development of New Formulations of Biologics: Expectations, Immunogenicity, and Safety for Subcutaneous Trastuzumab

Abstract

Subcutaneous (SC) trastuzumab has long been approved as a cancer treatment for early and advanced HER2-positive (HER2+) breast cancer by both the European Medicines Agency (EMA) and Agência Nacional de Vigilância Sanitária (ANVISA), the Brazilian National Health Surveillance Agency. A pivotal non-inferiority phase III trial, which aimed to provide a more convenient and cost-effective treatment in the HER2+ breast cancer neoadjuvant setting, showed that the SC group met prespecified efficacy endpoints and the SC formulation was considered as safe as the intravenous (IV) formulation. Considering the recent approval of several biosimilars, new SC formulations are also an interesting manufacturer strategy as these drugs can obtain patent protection. Despite being considered non-inferior to the IV formulation of trastuzumab, in clinical development, the SC formulation elicited higher immunogenicity, mainly related to overall anti-drug antibodies (ADAs); however, this finding was classified as clinically non-significant. In this article, we explore different aspects of the benefits and risks of the SC trastuzumab formulation according to published data.

Could pre-filled safety syringes facilitate the adoption of home administration for cancer patients?

“…However, efforts are ongoing to assess the feasibility of trastuzumab for home-administration for cancer patients in the future. 1 , 6 Such a change can improve patient quality of life and provide support to patients who live far from a hospital or who are less able to travel. Initial data for this treatment has been promising, with the safety profile of home-administration being consistent with that in a hospital setting.…”

Current Advancements in Addressing Key Challenges of Therapeutic Antibody Design, Manufacture, and Formulation

“…For example, polysorbates are commonly used in biologics as a stabilizing agent; however, their addition in high concentrations can denature proteins and cause adverse side effects such as injection site reactions [114,115,116]. Injectable mAb formulations are co-formulated with recombinant human hyaluronidase, specifically as a permeation enhancer for more efficient absorption into tissue, although the inclusion of this additional biologic adds further burden to the formulation’s viscosity and propensity to aggregate [5,8,25,26,27,28,117,118,119,120,121,122,123]. Antibody therapies for IV administration are prepared as lyophilised powder for reconstitution and further dilution, and injectable administrations are prepared as liquid-based formulations in pre-filled syringes.…”

Current and future roles of biosimilars in oncology practice (Review)

“…Ontruzant, produced by Samsung Bioepis, was the first biosimilar to trastuzumab Herceptin approved by the EMA in 2017. Ontruzant can be used as a monotherapy or in combination with chemotherapy or hormone therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (31). In addition, it can be used for early HER2-positive breast cancer in combination with chemotherapy and for metastatic gastric cancer (32).…”