FDA Approves Phesgo as Injection Treatment for HER2-positive Breast Cancers
The U.S. Food and Drug Administration (FDA) has approved Phesgo, an under-the-skin injection of Perjeta (pertuzumab) and Herceptin (trastuzumab) with hyaluronidase, as a faster and more convenient alternative to treat people with HER2-positive breast cancer.
The approval of this fixed-dose combination is for use with chemotherapy in early and metastatic breast cancers, the same indications for which the combination of intravenous (into-the-vein) Herceptin and Perjeta is approved.
The original formulations required intravenous infusions given over 2.5 hours. Phesgo was developed by Genentech as an equally effective and safe option, given to patients by a healthcare provider as an injection into the thigh that takes less than 10 minutes. This subcutaneous injection can be administered at a treatment center or a patient’s home.
“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an out-patient option for patients to receive trastuzumab and pertuzumab,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in an agency press release.
“At this critical time, we continue to expedite oncology product development,” Pazdur added. “This application was approved about four months ahead of the FDA goal date,” which was set for Oct. 18.
Herceptin and Perjeta, both developed by Genentech, are inhibitors of the HER2 receptor, a protein known to participate in breast cancer growth and survival, with distinct mechanisms of action. Perjeta works to prevent the HER2 protein from binding to the HER3 protein, and Herceptin prevents the HER2 protein from binding to similar HER2 proteins.
Herceptin and Perjeta are approved as intravenous therapies for HER2-positive breast cancers. A combination of these medicines plus chemotherapy is indicated for people with early breast cancer — before and after surgery — and for those whose cancer has spread to distant regions.
But this standard intravenous combination requires infusions of 2.5 hours for a loading dose, and one to 2.5 hours for subsequent maintenance infusions. Phesgo takes about eight minutes to be administered for the initial loading dose, and about five minutes for subsequent doses.
Phesgo’s approval was based on data from the FeDeriCa Phase 3 trial (NCT03493854), whose goal was to directly compare the original Herceptin-Perjeta combination to Phesgo.
In addition to pertuzumab and trastuzumab, its active ingredients, Phesgo also includes a man-made version of the hyaluronidase PH20 enzyme, the core of Halozyme Therapeutics’ proprietary ENHANZE drug-delivery technology. Hyaluronidase destroys components making up the connective tissue locally, enhancing the absorption of drugs and fluids injected under the skin.
FeDeriCa involved 500 patients with HER2-positive early breast cancer, who were randomly assigned to either the intravenous Perjeta-Hercetin combination or Phesgo, given in combination with chemotherapy before and after surgery.
Its main goal was to determine whether Phesgo was at least non-inferior to Perjeta-Hercetin in terms of minimum levels of Perjeta in the blood. Secondary goals included safety, minimum levels of Herceptin in the blood, and pathological complete responses — the proportion of patients with no detectable cancer at the time of surgery.
Results showed that the two treatment approaches led to similar amounts of Herceptin and Perjeta in the blood, and were similar in terms of safety, efficacy, and pharmacokinetic properties (the movement of a drug into, through, and out of the body).
Phesgo, however, led to higher rates of infusion-related reactions due to its route of administration.
A Phase 2 trial evaluating patient preference and satisfaction also found that most patients prefer the subcutaneous formulation, due to less time in the clinic and more conformable treatment administration.
The PHranceSCa study (NCT03674112) included 160 patients with early HER2-positive breast cancer who received Herceptin, Perjeta and chemo via intravenous infusions followed by surgery. They were then randomly assigned to either three cycles of the intravenous medicines before crossing to Phesgo for another three cycles, or to start with Phesgo followed by the intravenous medicines.
After the six cycles, patients were asked to choose which approach they preferred to complete the 18 cycles of their HER2-targeted treatment. Results showed that 85% of patients preferred the under-the-skin, fixed-dose Phesgo.
“The FDA approval of Phesgo reflects our commitment to improving outcomes for the many people living with HER2-positive breast cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Genentech, said in the company’s release.
“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,” Garraway added.
For those who qualify for Phesgo treatment, Genentech offers patient assistance programs. Go to Genentech Access Solutions for more information.
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