The U.S. Food and Drug Administration (FDA) will review Roche’s application seeking regulatory approval for a new formulation — given as a subcutaneous, or under-the-skin injection — of the fixed-dose combination of Perjeta (pertuzumab) and Herceptin (trastuzumab) for treating people with HER2-positive breast cancer.
This new formulation takes just minutes to administer, as compared with the 2.5 hours needed for the current treatment, given intravenously (into the vein), Roche said. If approved, the new formulation will help reduce the dosing time for patients receiving the combo treatment, which will be given together with intravenous, or IV chemotherapy.
The enzyme hyaluronidase also will be given together with the combination to assist in its delivery.
The FDA is expected to decide on the therapy’s approval by Oct. 18, Roche said.
“For more than two decades, our medicines have redefined the standard of care for people with HER2-positive breast cancer,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a press release.
“Today’s acceptance builds upon our commitment by potentially offering patients a faster way to administer Perjeta and Herceptin. We’re working with the FDA to bring this treatment option to patients as quickly as possible,” Garraway said.
The FDA has accepted Roche’s Biologics License Application (BLA) for the new Perjeta-Herceptin formulation. Unlike the more common application for an investigational new drug, or IND, a BLA covers a biologic product — a treatment that comes from a natural source, be it human, animal, or microorganism. Produced by biotechnology methods or other cutting-edge technologies, biologics can be composed of sugars, proteins, or nucleic acids, or a complex combinations of these substances, or may be living entities such as cells and tissues. This is in contrast to most medications, which are chemically synthesized with a known structure.
The BLA was supported by data from the FeDeriCa Phase 3 trial (NCT03493854), which showed that the safety, efficacy, and pharmacokinetic properties of standard IV infusions of Perjeta and Herceptin are identical when both medications are given by subcutaneous injections. Pharmacokinetics is the study of how a drug is absorbed, distributed, metabolized, and eliminated from the body — basically, what the body does to a drug.
FeDeriCa, which involved 500 patients with HER2-positive breast cancer, was the first study to compare the safety, efficacy, and pharmacokinetics of both Perjeta-Herceptin formulations, in combination with IV chemotherapy.
Data from FeDeriCa showed the trial met its primary goal of non-inferiority, meaning the subcutaneous Perjeta reached levels in the participants’ blood that were similar to those seen when the medication was given by IV.
Secondary non-inferiority endpoints also were met, with Herceptin delivered under the skin reaching levels in the blood identical to those observed when the medicine was administered intravenously.
The percentage of patients showing no signs of cancer following treatment — called a pathological complete response — also was identical in both formulations.
Moreover, analyses demonstrated that the safety profile of the subcutaneous fixed-dose combination of Perjeta-Herceptin was consistent with that of its standard IV formulation. The most common adverse events reported in both treatment groups included hair loss, nausea, diarrhea, and anemia. No new safety concerns were identified during the study.
In addition, the results showed this new mode of administration exponentially reduced the treatment dosing speed compared with the standard intravenous route.
Indeed, when given under the skin, the initial loading dose — basically, the first round of treatment — of the combination therapy takes approximately eight minutes to administer, and five additional minutes for each subsequent maintenance dose. In contrast, when given intravenously, the initial loading dose requires approximately 150 minutes or 2.5 hours to administer, and 60-150 additional minutes (one to 2.5 hours) for each subsequent maintenance dose.
When given a choice, most patients prefer to receive a medication by an under-the-skin injection instead of intravenously, mainly because it reduces the time spent at the hospital or clinic, previous studies have reported.
Roche currently is conducting a Phase 2 trial (NCT03674112) — called PHranceSCa — to investigate which formulation of the Perjeta-Herceptin combo therapy patients with HER2-positive early breast cancer prefer to receive. The company is planning to present interim results of that study at an upcoming medical meeting.
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