Ahead of the Arrival of US Biosimilar Trastuzumab, FDA Approves Subcutaneous Herceptin

The FDA has approved a subcutaneously administered version of the brand-name trastuzumab, Herceptin. The new formulation, trastuzumab and hyaluronidase-oysk, is a combination of the anticancer agent trastuzumab and an endoglycosidase that allows for the administration of higher volumes and enhanced absorption, and it has been approved under the name Herceptin Hylecta.
Kelly Davio
March 05, 2019
The FDA has approved a subcutaneously administered version of the brand-name trastuzumab, Herceptin. The new formulation, trastuzumab and hyaluronidase-oysk, is a combination of the anticancer agent trastuzumab and an endoglycosidase that allows for the administration of higher volumes and enhanced absorption, and it has been approved under the name Herceptin Hylecta.

Approval of the subcutaneously administered product was based on 2 randomized trials. First, the HannaH trial compared the subcutaneous trastuzumab to the infused product in 596 patients with HER2-positive breast cancer. Patients were randomized to receive 8 cycles of chemotherapy with either the subcutaneous or the intravenous trastuzumab, followed by surgery and an additional 10 cycles of their assigned trastuzumab therapy. In total, 45.5% of patients in the subcutaneous arm and 40.7% of patients in the intravenous arm had a pathological complete response.

Second, the SafeHER trial, a 2-cohort, non-randomized, multinational, open-label trial, assessed the overall safety and tolerability of the subcutaneous trastuzumab together with chemotherapy in 1864 patients with HER2-positive breast cancer. The trial, in which patients received a fixed dose of the drug every 3 weeks for 18 cycles, confirmed the safety and tolerability of the fixed dose of the drug.

Not only does a subcutaneous injection of trastuzumab provide advantages for patients who may prefer the faster injection to a lengthy visit to an infusion center, the newly approved formulation has also been shown to save on costs in other regulatory territories where the drug is already widely in use. The subcutaneous formulation of the product is approved and available in the European Union, where research from 3 centers in Spain demonstrated that using the subcutaneous product results in reduced per-patient costs for an 18-cycle treatment of €1132.43 ($1335.68). Those savings derive from provider time costs, the costs of consumables, and the cost of trastuzumab, as well as indirect costs such as reduced productivity associated with infusions.

The cost savings associated with the formulation could be a reason for concern on the part of biosimilar developers. To date, the FDA has approved 3 biosimilar trastuzumab products: Mylan and Biocon’s Ogivri, Celltrion’s Herzuma, and Samsung Bioepis’ Ontruzant, all of which have yet to launch in the US market. While it remains to be seen how deep a discount any of the biosimilar makers will offer for their intravenously administered products upon launch, questions remain about how substantial those discounts will need to be to overcome the appeal and the potential cost savings represented by a subcutaneous formulation of the originator drug.

However, some researchers have voiced questions about the subcutaneous version of the product that may make biosimilars a more appealing cost-saving option. Writing in Pharmaceutical Medicine, authors recently pointed out that one of the main concerns with trastuzumab’s biological activity is its interaction with pertuzumab to treat HER2-positive cancer, and interactions among HER2 receptor, pertuzumab, and trastuzumab–anti-drug antibody complexes have not yet been fully evaluated with respect to the subcutaneous product. The phase 3 SAPPHIRE study did evaluate the safety, tolerability, and efficacy of intravenous pertuzumab plus subcutaneous trastuzumab and a taxane, but the small population enrolled in the study made it difficult to draw conclusions. 

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