Roche's Fixed-Dose Subcutaneous Perjeta/Herceptin Combination Meets Primary Endpoint in Phase III FeDeriCa Trial

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Recently, Roche announced that the Phase III clinical study FeDeriCa, evaluating the subcutaneous (SC) fixed-dose combination of Perjeta and Herceptin for the treatment of HER2-positive early breast cancer (eBC), had met its primary endpoint.

This is an international, multicenter, two-arm, randomized, open-label study conducted in patients with HER2-positive early breast cancer (eBC) receiving neoadjuvant (preoperative) and adjuvant (postoperative) therapy. The study evaluated the pharmacokinetics, efficacy, and safety of the subcutaneous (SC) fixed-dose combination formulation of Perjeta and Herceptin administered alongside chemotherapy, compared with standard intravenous (IV) administration of Perjeta and Herceptin combined with chemotherapy. The primary endpoint was the trough concentration of Perjeta in blood at the specified dosing interval. Secondary endpoints included safety, the trough concentration of Herceptin in blood at the specified dosing interval, and pathological complete response.

The results demonstrated that the study met its primary endpoint: the subcutaneous (SC) fixed-dose combination formulation of Perjeta and Herceptin, administered with chemotherapy, showed non-inferiority in terms of serum Perjeta levels compared to the standard intravenous (IV) regimen of Perjeta and Herceptin combined with chemotherapy. Regarding safety, the profile was consistent with the known safety of IV-administered Perjeta and Herceptin.

The complete data from this study will be presented at an upcoming medical conference and submitted to regulatory authorities worldwide.

Currently, the standard intravenous (IV) loading dose of Perjeta and Herceptin takes approximately 150 minutes, with subsequent maintenance infusions taking approximately 60–150 minutes. In contrast, the subcutaneous (SC) formulation in this study took only approximately 8 minutes for administration, with subsequent maintenance dosing taking only approximately 5 minutes.

Perjeta and Herceptin Fixed-Dose Combination Subcutaneous Formulation is a new drug that combines Perjeta, Herceptin, and Halozyme Therapeutics’ Enhanze drug delivery technology.

The mechanisms of action of Perjeta and Herceptin are complementary, as both bind to the HER2 receptor but at different sites. The combination of these two agents is considered to provide more comprehensive, dual blockade of the HER2 signaling pathway. To date, the standard intravenous formulation of Perjeta in combination with Herceptin and chemotherapy has been approved in over 100 countries worldwide for the treatment of early-stage and metastatic HER2-positive breast cancer.

The ENHANZE drug delivery technology enables and optimizes subcutaneous (SC) drug delivery for appropriate combination therapy. This technology is based on a proprietary recombinant human hyaluronidase PH20, an enzyme that temporarily degrades hyaluronic acid, a glycosaminoglycan or natural sugar chain in the body, to facilitate the dispersion and absorption of other injectable therapeutic agents.

Analysts have pointed out that this innovative subcutaneous (SC) injection formulation will bring tangible benefits to patients and also provide some protection for Roche’s HER2 franchise, shielding it from competition by lower-priced biosimilars.

Earlier this year, the subcutaneous (SC) injection formulation of Herceptin—Herceptin Hylecta—received approval from the U.S. FDA, with an administration time of only approximately 2–5 minutes. In the European Union, the SC injection formulation of Herceptin was approved for market launch as early as 2013, but this was insufficient to halt the overall decline in Herceptin sales. Currently, multiple intravenous (IV) injection formulations of Herceptin are marketed in Europe. In the first half of this year, Herceptin’s sales in the region shrank significantly by 45%, contributing to a 9% decrease in total revenue to $3.2 billion. This decline was partially offset by growth in emerging markets such as China.

In the United States, Amgen/Allergan’s intravenous (IV) injectable biosimilar of Herceptin has been launched, priced 15% lower than the originator product. Roche previously attempted to secure a sales injunction against the biosimilar but was unsuccessful. By late 2019/early 2020, at least four additional Herceptin biosimilars are expected to enter the U.S. market, exposing approximately 50% of the drug’s sales to competitive threats.

Perjeta’s European patent protection expires in 2023, and its U.S. patent protection expires in 2024. Driven by data demonstrating enhanced efficacy of Herceptin when used in combination, along with broad penetration in the adjuvant treatment of breast cancer, the drug’s sales have grown rapidly. In the first half of 2019, sales increased by one-third, reaching $1.8 billion.

If approved, the new fixed-dose combination subcutaneous injection of Perjeta and Herceptin will provide an alternative therapeutic option to the combination of biosimilar Herceptin and Perjeta, potentially mitigating the impact of biosimilars on Roche’s HER2 franchise.

References:

1、Roche’s fixed-dose subcutaneous combination of Perjeta and Herceptin showed non-inferiority when compared to intravenous formulations for people with HER2-positive breast cancer

2、As ‘big three’ oncology meds lose sales, Roche looks to file subcutaneous breast cancer combo

3、Roche preps filings for Herceptin/Perjeta combination