On September 9, 2017 Amgen (NASDAQ:AMGN) and Allergan plc. (NYSE:AGN) reported data from a Phase 3 study evaluating the efficacy and safety of ABP 980, a Herceptin (trastuzumab) biosimilar, compared with the originator product in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (Press release, Amgen, SEP 9, 2017, View Source [SID1234520439]). Results from the neoadjuvant efficacy phase of the study, including pathologic complete response assessed both by local investigators and also by independent pathology review, were presented today during a poster discussion at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress. Efficacy, safety and immunogenicity data support ABP 980 as a trastuzumab biosimilar and add to the totality of evidence currently under review by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).

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"Biosimilars have the potential to provide more patients access to high-quality therapies with proven safety and efficacy profiles," said Serafin Morales, M.D., medical oncologist, University Hospital Arnau de Vilanova, Lleida, Spain. "The results presented today add to the data package demonstrating similarity between ABP 980 and trastuzumab."

The co-primary endpoints of the study were risk difference (RD) and risk ratio (RR) of pathologic complete response in breast tissue and axillary lymph nodes, and the prespecified equivalence margins were +/-13 percent for RD and 0.759 to 1.318 for RR. According to local review, 48 percent and 40.5 percent of patients in the ABP 980 arm and trastuzumab arm, respectively, achieved pathologic complete response. RD and RR of pathologic complete response were 7.3 percent (90 percent CI: 1.2, 13.4) and 1.19 (90 percent CI: 1.033, 1.366) respectively. Based on central independent review, which was conducted as part of a sensitivity analysis, 47.8 percent and 41.8 percent in the ABP 980 arm and trastuzumab arm, respectively, achieved pathologic complete response. RD and RR of pathologic complete response respectively were 5.8 percent (90 percent CI: -0.5, 12.0) and 1.14 (90 percent CI: 0.993, 1.312).

Frequency, type and severity of adverse events were similar between ABP 980 and trastuzumab. No new safety signals compared to the known safety profile of trastuzumab were detected.

"At the heart of Amgen’s commitment to biosimilars is our mission to serve patients. We are leveraging our more than 35 years of biotechnology experience and using the same personnel, services and manufacturing expertise from the company’s innovative business to produce high-quality, reliably supplied biosimilars for some of the most complex diseases," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The results presented today reinforce the potential of ABP 980 for breast cancer patients, and we look forward to continued discussions with regulatory authorities."

"Allergan is proud to be collaborating with Amgen on the development of several oncology biosimilars that require significant expertise, infrastructure and investment to ensure safe therapies for patients," said David Nicholson, Ph.D., chief research and development officer, Allergan. "We are excited about the progress of ABP 980 and are committed to its development in hopes of providing patients with an effective alternative option."

Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of 10 biosimilars in its portfolio, one of which has been approved by the FDA and European authorities.

ABP 980 Phase 3 Study Design
The ABP 980 Phase 3 LILAC study was a randomized, multicenter, double-blinded, active-controlled study (study number 20120283) that evaluated safety and efficacy of ABP 980 compared to trastuzumab in adult female patients with HER2-positive early breast cancer. There were 725 patients randomized, with 364 patients in the ABP 980 group and 361 patients in the trastuzumab group.

In the neoadjuvant phase, enrolled patients received run-in chemotherapy consisting of epirubicin and cyclophosphamide (EC) every three weeks (Q3W) for four cycles. Once run-in chemotherapy was completed, patients with adequate cardiac function were randomized 1:1 to receive ABP 980 or trastuzumab, plus paclitaxel, Q3W for four cycles. Surgery (breast and sentinel node or axillary lymph node resection) was complete three to seven weeks after the last dose of either ABP 980 or trastuzumab in the neoadjuvant phase, and pathologic complete response was analyzed.

In the adjuvant phase, following surgery, patients received ABP 980 or trastuzumab Q3W for up to one year from the first day either product was administered in the neoadjuvant phase. Patients who received ABP 980 during the neoadjuvant phase continued to receive ABP 980 Q3W for the adjuvant phase. Patients who received trastuzumab during the neoadjuvant phase either underwent a single switch to ABP 980 or continued on trastuzumab Q3W for the adjuvant phase. The allocation to a treatment group during the neoadjuvant or adjuvant phase occurred by randomization, as did the single switch from trastuzumab to ABP 980 after the neoadjuvant phase.

The primary analysis was conducted when the last patient completed the surgery following the neoadjuvant therapy. Statistical equivalence was assessed by comparing the confidence interval of the RD and RR of the pathologic complete response in breast tissue and axillary lymph nodes with the prespecified equivalence margins.

About HER2-Positive Early Breast Cancer
HER2-positive early breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells.1 Approximately 20 percent of all breast cancers are HER2-positive.2 Breast cancer is the most common cancer in Europe for females, and the most common cancer overall, with more than 464,000 new cases diagnosed each year.3 HER2-positive breast cancers tend to grow and spread more aggressively than HER2-negative breast cancers.1

About ABP 980
ABP 980 is being developed as a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody approved in many regions for the treatment of HER2-overexpressing early breast cancer, adjuvant breast cancer, metastatic breast cancer and metastatic gastric cancer. The active ingredient of ABP 980 is a humanized monoclonal antibody that has the same amino acid sequence as trastuzumab. ABP 980 has the same pharmaceutical dosage form and strength as trastuzumab. In March and July of 2017 respectively, Amgen and Allergan submitted a Marketing Authorization Application to the EMA and a Biologics License Application to the FDA for ABP 980.