Roche announced that the US Food and Drug Administration (US FDA) has approved Phesgo, a fixed-dose combination of Perjeta (pertuzumab) and Herceptin (trastuzumab) with hyaluronidase, administered by subcutaneous (SC; under the skin) injection in combination with intravenous (IV) chemotherapy, for the treatment of early and metastatic HER2-positive breast cancer. This is the first time that Roche has combined two monoclonal antibodies that can be administered by a single SC injection.
“The US FDA approval of Phesgo reflects our commitment to improving outcomes for the many people living with HER2-positive breast cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Phesgo offers a treatment administration that supports the needs and preferences of individual patients, and helps to meet the increasing demand across the healthcare system for faster and more flexible treatment options.”
Phesgo is available in one single-dose vial. Administration can take approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for a sequential infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines.
Phesgo can be administered by a healthcare professional in a treatment centre or at a patient’s home.
The approval is based on results from the pivotal phase III FeDeriCa study, which met its primary endpoint with Phesgo showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough), when compared to IV administration of Perjeta. The safety profile of Phesgo with chemotherapy was comparable to IV administration of Perjeta plus Herceptin and chemotherapy, and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhoea and anaemia.
The phase II PHranceSCa study showed that 85% (136/160) of people receiving treatment for HER2-positive breast cancer preferred treatment under the skin to IV administration due to less time in the clinic and more comfortable treatment administration.
FeDeriCa is an international, multi-centre, two-arm, randomised, open-label, pivotal phase III study evaluating the pharmacokinetics, efficacy and safety of subcutaneous injection of Phesgo in combination with chemotherapy, compared with standard intravenous (IV) infusions of Perjeta and Herceptin in combination with chemotherapy, in 500 people with HER2-positive early breast cancer treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings.
The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough), when compared to IV administration of Perjeta. Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pathological complete response, meaning there is no tumour tissue detectable in the tissue removed at the time of surgery.
Data from the FeDeriCa study were presented at the San Antonio Breast Cancer Symposium in December 2019. The FeDeriCa study met its primary endpoint of non-inferior levels of Perjeta in the blood. The geometric mean ratio (GMR; a type of average used when assessing pharmacokinetics) for the primary endpoint was 1.22 (90% CI: 1.14 to 1.31), with the lower limit of the 90% CI of the GMR=1.14=0.80 (the pre-specified non-inferiority margin).
A secondary endpoint of non-inferior levels of Herceptin was also met, with blood concentrations for people receiving the fixed-dose combination non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI: 1.24 to 1.43]; lower limit of 90% CI of GMR=1.24=0.80). A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals.
PHranceSCa is a phase II, randomised, multi-centre, multinational, open-label, cross-over study evaluating patient preference for and satisfaction with subcutaneous administration of Phesgo in 160 people with HER2-positive early breast cancer. All patients completed neoadjuvant (before surgery) treatment with Perjeta, Herceptin and chemotherapy and had surgery before randomisation. The primary endpoint of the study is the percentage of participants who indicate that they prefer treatment with Phesgo compared to the standard intravenous (IV) formulations of Perjeta and Herceptin.
Secondary endpoints include participant-reported satisfaction and health-related quality of life outcomes; healthcare professionals' perceptions of time and resource use and convenience compared with IV formulations; as well as the safety and efficacy of each study regimen.
Phesgo is a new fixed-dose subcutaneous (SC) formulation that combines Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze drug delivery technology. This is the first time that Roche has combined two monoclonal antibodies that can be administered by a single SC injection