Roche’s Fixed-Dose Subcutaneous Combination Phesgo (Pertuzumab/Trastuzumab/Hyaluronidase) Receives CHMP Positive Opinion for HER2-Positive Breast Cancer with Administration Time of Only 5–8 Minutes

Nov. 15, 2020 /Bio ValleyBIOON/ -- Roche recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Phesgo (pertuzumab/trastuzumab/hyaluronidase) 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-positive breast cancer.Breast CancerPatient. Both Perjeta and Herceptin are HER2-targeted monoclonal antibodies.

The CHMP opinion will now be submitted to the European Commission (EC) for review, which typically issues a final decision within two months. 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.

In June this year, Phesgo received U.S.FDAApproved for the same indications mentioned above. Notably, this marks the first time Roche has combined two monoclonal antibodies into 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 in 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 administered over approximately 5 minutes. In contrast, the sequential intravenous infusion of standard 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 a treatment center or in the patient’s home.

Levi Garraway, M.D., Chief Medical Officer and Global Head of Product Development at Roche, stated: “We are committed to transforming the lives of patients with breast cancer, going beyond improving efficacy alone. Today’s positive opinion from the CHMP represents another significant step toward redefining the standard of care for patients with HER2-positive breast cancer in Europe, offering a faster and less invasive Perjeta + Herceptin treatment regimen.”

United StatesFDAThe approval and the positive opinion from the EU CHMP were both 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 IV chemotherapy showed non-inferiority in terms of Perjeta levels in the blood (pharmacokinetics), as well as comparable efficacy and safety, compared to the standard intravenous (IV) regimen of Perjeta + Herceptin + chemotherapy.

The study met its primary endpoint: subcutaneous (SC) administration of Phesgo demonstrated non-inferiority in trough serum concentrations (Ctrough) of Perjeta over 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 pre-specified non-inferiority margin). The secondary endpoint of non-inferior Ctrough for Herceptin was also met, with Herceptin serum 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 for this study 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, another secondary endpoint, was comparable between the two treatment groups. Overall pCR was achieved in 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 combined with chemotherapy 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 common adverse reactions in both groups were alopecia, nausea, diarrhea, andAnemia. The study did not identify any new safety signals, including no significant differences in cardiotoxicity. The most commonAdverse ReactionsAlopecia, nausea, diarrhea, and anemia.

In previous studies, compared with intravenous administration of the same drug, most patients preferred subcutaneous (SC) injection, with the most common reason being the shorter time required for clinical administration. Data from Roche’s Phase II PHranceSCa study also showed that 85% (136/160) of patients with HER2-positive breast cancer preferred subcutaneous injection over intravenous infusion due to shorter clinic stays 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 both heterodimerization and homodimerization of HER2. Although Perjeta and Herceptin share the same mechanism of action—targeting and binding to the HER2 receptor—they bind to 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: CHMP Recommends EUapproval of Roche’s Phesgo (fixed-dose combination of Perjeta and Herceptin for subcutaneous injection) for HER2-positive breast cancer