HER2+ Breast Cancer Breakthrough: Roche’s Fixed-Dose Subcutaneous Phesgo (Perjeta + Herceptin) Approved by FDA with 5–8 Minute Administration

June 30, 2020 News /BioValleyBIOON/ -- Roche recently announced that the U.S. Food and Drug Administration (FDA) has approved Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf) for subcutaneous injection. This drug is a fixed-dose combination (FDC) of Perjeta (pertuzumab), Herceptin (trastuzumab), and hyaluronidase, administered via subcutaneous (SC) injection in combination with intravenous (IV) chemotherapy for the treatment of early-stage and metastatic HER2-positiveBreast CancerPatient. Both Perjeta and Herceptin are HER2-targeted monoclonal antibodies.

Phesgo was developed using Halozyme’s Enhanze drug delivery technology, which is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20). This enzyme temporarily degrades hyaluronic acid in the body, facilitating faster dispersion and absorption of injected drugs, thereby enabling subcutaneous administration.

Notably, this marks the first time Roche has combined two monoclonal antibodies for administration via a single subcutaneous (SC) injection. The approval of Phesgo provides a rapid, minimally invasive treatment option for patients with HER2-positive breast cancer who are currently receiving intravenous (IV) Perjeta and Herceptin therapy. Compared with IV administration, Phesgo is delivered via subcutaneous injection and can be administered within minutes, significantly reducing the time patients spend receiving treatment.

Phesgo is supplied in single-dose vials, with the initial loading dose administered over approximately 8 minutes and subsequent maintenance doses over approximately 5 minutes. In contrast, sequential infusion of standard intravenous formulations of Perjeta and Herceptin requires approximately 150 minutes for the initial dosing, followed by 60–150 minutes for each subsequent maintenance infusion. Phesgo can be administered by healthcare professionals either at treatment centers or in patients’ homes.

Levi Garraway, M.D., Chief Medical Officer and Global Head of Product Development at Roche, stated: “FDA“The approval of Phesgo reflects our commitment to improving outcomes for patients with HER2-positive breast cancer. The subcutaneous administration of Phesgo supports individual patient needs and preferences, while helping to meet the healthcare system’s growing demand for faster and more flexible treatment options.”

This approval is based on the results of the pivotal Phase III FeDeriCa study. The study demonstrated that, in eligible patients with HER2-positive early breast cancer (eBC), the subcutaneous (SC) administration of Phesgo combined with intravenous (IV) chemotherapy showed non-inferiority in terms of Perjeta blood levels (pharmacokinetics), as well as comparable efficacy and safety, compared to the standard IV regimen of Perjeta + Herceptin + chemotherapy.

The study met its primary endpoint: subcutaneous (SC) administration of Phesgo demonstrated non-inferiority in Perjeta trough concentrations (Ctrough) during the dosing interval compared with intravenous (IV) infusion of Perjeta. The geometric mean ratio (GMR; a type of average used in pharmacokinetic assessments) for the primary endpoint was 1.22 (90% CI: 1.14–1.31), with the lower bound of the 90% CI for a GMR of 1.14 being ≥0.80 (the prespecified non-inferiority margin). The secondary endpoint of non-inferior Ctrough for Herceptin was also met, with Herceptin blood concentrations in patients receiving Phesgo being non-inferior to those in patients receiving IV Herceptin (GMR=1.33 [90% CI: 1.24–1.43]; the lower bound of the 90% CI for a GMR of 1.24 was ≥0.80). A non-inferiority endpoint was selected to ensure that patients received adequate doses of Perjeta and Herceptin within the same treatment interval compared with the established IV dosing regimen. Furthermore, the overall pathological complete response (pCR) rate, as a secondary endpoint, was comparable between the two treatment groups. Overall pCR was achieved by 59.7% of patients receiving the fixed-dose combination (FDC) and 59.5% of patients receiving IV Perjeta and Herceptin, with a difference of 0.15% (95% CI: –8.67 to 8.97).

The safety profile of the FDC combination regimen was comparable to that of intravenous Perjeta plus Herceptin combined with chemotherapy, with no new safety signals identified, including no significant difference in cardiotoxicity. The most commonAdverse ReactionsHair loss, nausea, diarrhea, andAnemia。

The study did not identify any new safety signals, including no significant difference in cardiotoxicity. The most commonAdverse ReactionsAlopecia, nausea, diarrhea, and anemia.

In previous studies, most patients preferred subcutaneous (SC) injection over intravenous administration of the same drug, primarily due to the shorter time required for clinical administration. Data from Roche’s Phase II PHranceSCa study also demonstrated that 85% (136/160) of patients with HER2-positive breast cancer preferred subcutaneous injection over intravenous infusion, citing shorter clinic visits and greater treatment comfort.

Breast cancer is the most common type of cancer in women, with over 2 million new cases diagnosed globally each year. HER2-positive breast cancer is a particularly aggressive subtype, accounting for approximately 15–20% of all breast cancer cases. Among patients with HER2-positive early-stage breast cancer (eBC) treated with Herceptin plus chemotherapy, approximately one-quarter still experience disease recurrence or death within 10–11 years, with even higher rates of recurrence or death observed in high-risk eBC patients.

Perjeta is a novel anti-HER2 agent that exerts its anti-HER2 effects by inhibiting HER2 heterodimerization and homodimerization. Perjeta and Herceptin share the same mechanism of action, both targeting and binding to the HER2 receptor, albeit at distinct epitopes. The combination of these two agents provides more comprehensive blockade of the HER2 signaling pathway, thereby inhibiting cancer cell growth and survival.

The standard regimen of intravenous Perjeta plus intravenous Herceptin and chemotherapy (Perjeta regimen) has been approved in more than 100 countries worldwide for the treatment of early-stage and metastatic HER2-positive breast cancer. In the neoadjuvant (preoperative) setting for early breast cancer (eBC), the Perjeta regimen nearly doubled the pathological complete response (pCR) rate compared with Herceptin plus chemotherapy. Furthermore, in the adjuvant (postoperative) setting for eBC, the Perjeta regimen significantly reduced the risk of invasive disease recurrence or death. In metastatic disease, the Perjeta regimen demonstrated unprecedented survival benefits in patients with first-line HER2-positive metastatic breast cancer.

In China, the Perjeta + Herceptin + chemotherapy regimen was approved in December 2018 for the adjuvant treatment of patients with HER2-positive early breast cancer (eBC) at high risk of recurrence. This approval marks the entry of breast cancer treatment in China into a new era! Data from the global pivotal Phase III adjuvant therapy study demonstrated that, compared with the standard therapy of Herceptin + chemotherapy, the adjuvant treatment with the Perjeta + Herceptin + chemotherapy regimen significantly prolonged invasive disease-free survival in patients with HER2-positive eBC at high risk of recurrence.Adverse ReactionsControllable, with a clear clinical benefit/risk advantage. (Bioon.com)

Original Source:FDA approves Roche’s Phesgo (fixed-dose combination of Perjeta and Herceptin for subcutaneous injection) for HER2-positive breast cancer