FDA Approves Under-the-skin Formulation of Herceptin for Certain Breast Cancers

The U.S. Food and Drug Administration (FDA) has approved an under-the-skin formulation of Genentech‘s breast cancer treatment Herceptin (trastuzumab), called Herceptin Hylecta. Also by Genentech, the treatment consists of a combination of trastumuzab and recombinant human hyaluronidase PH20, a protein that helps deliver the antibody under the skin.

“Over the past 20 years, Herceptin has significantly advanced treatment of HER2-positive breast cancer,” Sandra Horning, MD, Genentech’s chief medical officer and head of global product development, said in a press release. “The approval of Herceptin Hylecta gives physicians and patients in the United States a new option to select treatment based on individual needs and preferences.”

The new treatment contains trastuzumab, the same antibody used in intravenous Herceptin, which targets the HER2 protein — involved in breast cancer growth and survival — and the recombinant human hyaluronidase PH20 — an enzyme that temporarily destroys large sugar molecules in the body, facilitating trastuzumab delivery under the skin.

This recombinant enzyme is part of the proprietary drug delivery technology Enhanze, developed by Halozyme Therapeutics.

As a result, unlike the standard intravenous injections of Herceptin that could take between 30 to 90 minutes to administer, the combined therapy can be administered by a subcutaneous (under the skin) injection in two to five minutes.

The new therapy regimen has been approved for the treatment of patients with HER2-positive tumors at the earliest stages of disease (in combination with chemotherapy) and for patients with advanced HER2-positive metastatic breast cancer who had already been treated with at least one chemotherapy agent after cancer spreading (together with paclitaxel or alone).

The FDA’s approval was based on results from two Phase 3 clinical trials — HannaH (NCT00950300) and SafeHER (NCT01566721) — and one Phase 2 trial, called PrefHER (NCT01401166).

HannaH compared the efficacy of Herceptin Hylecta to conventional intravenous Herceptin, both together with chemotherapy, before and after patients underwent surgery.

Results showed that patients treated with subcutaneous injections of Herceptin Hylecta had identical concentrations of trastuzumab in the blood compared to those receiving intravenous injections of Herceptin (78.7 micrograms/mL vs. 57.8 micrograms/mL). In addition, both treatment regimens led to similar rates of pathological complete response (45.4% vs. 40.7%), which refers to the lack of malignant cancer cells in the breast.

Over the course of SafeHER, a trial intended to assess the safety and tolerability of Herceptin Hylecta compared to Herceptin, no new safety signals were found, and the safety and tolerability profiles of both treatments were considered equivalent.

In PrefHER, a study designed to evaluate patients’ treatment preference, findings showed that most patients (86%) preferred to be treated with subcutaneous injections of Herceptin Hylecta, rather than intravenous injections of Herceptin.

Pooled data from all studies involving women with early-stage breast cancer showed the most common side effects associated with Herceptin Hylecta treatment were fatigue, joint pain, diarrhea, skin reactions at the injection site, upper respiratory infections, skin rash, muscle pain, nausea, headache, swelling, flushing, fever, cough, and pain at the extremities.

The FDA and Genentech encourage patients to seek medical attention immediately should they experience any of these side effects and to report any additional ones they may have during treatment.