Fixed-Dose, Subcutaneous Pertuzumab and Trastuzumab Combination Meets Primary End Point in Phase 3 Study

The Center for Biosimilars Staff

By providing time-saving options for treatment, Roche may be able to secure market share for its innovator biologics if savings in terms of chair time for patients are able to offset the eventual price discounts made available by biosimilar developers for their products.

Roche’s Genentech has announced that a phase 3 study of a proposed fixed-dose combination of its pertuzumab (Perjeta) and trastuzumab (Herceptin) has met its primary end point of trough serum concentration of pertuzumab during cycle 7.

The FeDeriCa study, an international, multicenter, 2-arm, randomized open-label study is designed to evaluate the safety and efficacy of a subcutaneous injection of the antibody combination together with chemotherapy in patients with HER2-positive early breast cancer in the neoadjuvant and adjuvant settings. In total, 500 patients were randomized to receive either pertuzumab and trastuzumab intravenously together with chemotherapy, or to receive the subcutaneous combination plus chemotherapy.

According to Genentech, in addition to meeting the primary end point, the safety profile for the combination therapy was consistent with the known safety profiles of the 2 drugs when administered intravenously.

The combination offers the time-saving benefit of an approximately 8-minute loading dose followed by 5-minute maintenance doses, compared with 150-minute loading doses and 60- to 150-minute maintenance doses of the intravenous therapies.

“With this single injection under the skin, people with HER2-positive breast cancer receiving Perjeta and Herceptin can have a faster treatment option,” said Sandra Horning, MD, chief medical officer and head of global product development at Roche. “Our medicines have helped millions of people living with HER2-positive breast cancer and this latest development is particularly exciting as, for the first time, we have combined two therapeutic antibodies as a single subcutaneous formulation.”

The proposed combination is the latest subcutaneous option developed by Roche in conjunction with Halozyme Therapeutics; in 2006, Roche entered into an agreement with Halozyme to develop subcutaneous versions of several of its top-selling biologics, including rituximab (MabThera) and trastuzumab (Herceptin), both of which now have approved subcutaneous options in multiple regulatory territories.

Halozyme’s approach is based on a proprietary recombinant human hyaluronidase PH20, an enzyme that temporarily degrades hyaluronan in order to aid in the dispersion and absorption of other injected therapeutic drugs.

Such subcutaneously administered options for Roche’s innovator products are emerging as biosimilar competition begins to take hold in earnest in the European marketplace, where multiple biosimilars of intravenously infused trastuzumab and rituximab have launched. In the United States, just one intravenous trastuzumab biosimilar—Amgen’s Kanjinti—is commercially available, but additional approved agents are expected to enter the marketplace in the coming months. While no pertuzumab biosimilars are on the immediate horizon, by providing time-saving options for treatment, Roche may be able to secure market share for its innovator biologics if savings in terms of chair time for patients are able to offset the eventual price discounts made available by biosimilar developers for their products.