The FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended accelerated approval of a new indication for Genentech’s Perjeta® (pertuzumab) as the nation’s first treatment allowed before surgery in people with HER2-positive, early-stage breast cancer.

ODAC concluded that the benefits of a Perjeta regimen for neoadjuvant treatment outweighed its risks in its recommendation, approved 13-0 with one abstention. The action sets the stage for the FDA to add the new indication, which would make Perjeta also the first treatment to be approved based on pathological complete response (pCR) data, with no tumor tissue detectable at the time of surgery.

The FDA plans to make a final decision before Oct. 31. If the agency grants final approval as expected, it would be a model for an accelerated FDA pathway for bringing to market new drugs for the earlier stages of breast cancer and other forms of the disease where treatment is likely to have a greater impact.

Genentech, a subsidiary of Roche, won FDA approval in June 2012 for Perjeta, but for use after surgery in people with HER2-positive metastatic breast cancer.

Perjeta is designed specifically to prevent the HER2 receptor from pairing with other HER receptors (EGFR/HER1, HER3, and HER4) on the surface of cells. The combination of Perjeta and Herceptin® (trastuzumab) is thought to provide a more comprehensive blockade of HER signaling pathways. Perjeta and Herceptin are also believed to complement each other, as both bind to the HER2 receptor, but to different places.

ODAC said its recommendation was based on results submitted by Roche Genentech from two Phase II studies of Perjeta in high-risk, HER2-positive, early-stage breast cancer (NEOSPHERE and TRYPHAENA), as well as on longer-term safety data from the Phase III CLEOPATRA study of Perjeta in HER2-positive metastatic breast cancer.

NEOSPHERE (NEOadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) was conducted in 417 people with newly diagnosed HER2-positive, locally advanced, inflammatory or early-stage breast cancer with tumors greater than 2 cm. The study found that treatment with Perjeta, Herceptin, and docetaxel chemotherapy significantly improved the rate of total pCR to 39.3% vs. 21.5% for patients taking Herceptin and docetaxel alone—a 17.8% improvement.

TRYPHAENA (ToleRabilitY of Pertuzumab, Herceptin, and AnthracyclinEs in NeoAdjuvant breast cancer) was conducted in 225 people with HER2-positive, locally advanced, inflammatory or early stage breast cancer with tumors greater than 2 cm. pCR rates ranged from 54.7% for anthracycline-based chemotherapy followed by Perjeta, Herceptin, and docetaxel, to 63.6% for Perjeta, Herceptin, docetaxel, and carboplatin chemotherapy.

To address concerns about longer-term effects of Perjeta use, Genentech has proposed as a confirmatory study the ongoing Phase III APHINITY study, designed to further evaluate Perjeta after surgery. APHINITY will compare a combination of Perjeta, Herceptin, and chemotherapy with Herceptin and chemotherapy in people with HER2-positive, early-stage breast cancer.

APHINITY has completed enrollment with approximately 4,800 people. The primary endpoint is invasive disease-free survival (IDFS). Data from the study are expected in 2016, Genentech said.

Sales of Perjeta nearly doubled to CHF 108 million (about $116 million) during the first half of this year, from CHF 56 million ($60.2 million) in all of 2012.

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