Trastuzumab Biosimilar Approaches European Approval

Sean E. Harper, MD

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the marketing authorization of ABP 980, a biosimilar to trastuzumab (Herceptin).

If the European Commission now follows the CHMP recommendation, ABP 980 would be approved in in the European Union, Norway, Iceland, and Liechtenstein as a treatment for patients with HER2-positive metastatic breast cancer, HER2-positive early breast cancer, and HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction.

“The positive opinion issued by the CHMP for ABP 980 marks an important step for our biosimilar portfolio, as it's our second oncology biosimilar to reach this important milestone, and further underscores our commitment to providing the oncology community access to high-quality cancer therapies,” Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement.

“We look forward to continuing our work with Allergan and European regulatory authorities to bring additional options to patients with cancer,” added Harper.

Amgen and Allergan are collaborating on the development and commercialization of 4 oncology biosimilars, including ABP 980. The companies filed for marketing authorization approval in the EU based in part on results from the phase III LILAC study, which examined the biosimilar in women with HER2-positive early breast cancer.

Data were presented at the 2017 ESMO Congress for 725 patients from the LILAC trial. Following run-in anthracycline-based chemotherapy, patients were randomized to neoadjuvant paclitaxel plus ABP 980 (n = 364) or trastuzumab (n = 361) every 3 weeks for 4 cycles. Patients continued to the adjuvant phase on IP Q3W for up to 1 year.

The primary endpoints were risk difference (RD) and risk ratio (RR) of pathologic complete response (pCR) in breast tissue and axillary lymph nodes of tumor samples. According to the study design, the criteria for clinical similarity were met if the 2-sided 90% CIs for RD and RR were within the bioequivalence margin of -13% to 13% for RD and 0.759 to 1.318 for RR. Safety was a secondary endpoint for the trial.

According to local review, 48.0% of patients in the ABP 980 arm and 40.5% in trastuzumab arm achieved pCR. Risk difference of pCR was 7.3% (90% CI, 1.2-13.4) and RR of pCR was 1.19 (90% CI, 1.033-1.366), with the upper bound CI slightly exceeding the equivalence margin.

Based on central independent review conducted as part of a sensitivity analysis, 47.8% in the ABP 980 arm and 41.8% in the trastuzumab arm achieved pCR. Risk difference of pCR was 5.8% (90% CI, -0.5 to 12.0) and RR of pCR was 1.14 (90% CI, 0.993-1.312), contained within the equivalence margin.

The incidence of any-grade adverse events (AEs) was 80.2% with BP 980 and 79.5% with trastuzumab. The rates of grade ≥3 AEs were 14.8% versus 14.1%, respectively. The most common AEs (ABP 980 vs trastuzumab) were arthralgia (17.3% vs 15.2%), asthenia (14.8% vs 16.3%), neutropenia (14.6% vs 12.5%), peripheral neuropathy (13.7% vs 11.9%), and anemia (11.0% vs 10.2%).

In December 2017, the US FDA approved the trastuzumab (Herceptin) biosimilar MYL-1401O (Ogivri; trastuzumab-dkst). The approval was supported in part by data from HERiTAge, a 2-part, multicenter, double-blind, randomized, parallel-group study. Patients with measurable HER2-positive metastatic breast cancer who had not received prior chemotherapy or trastuzumab for metastatic disease were randomly assigned to MYL-1401O (n =230) or trastuzumab with docetaxel or paclitaxel (n = 228).

Patients underwent a minimum of 8 cycles in Part 1 of the trial, with trastuzumab continuing until progression. Both forms of trastuzumab were administered with a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg every 3 weeks.

In part 2, patients who had stable disease or better could continue with MYL-1401O or trastuzumab. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival, overall survival, time to progression, safety, and tolerability.

MYL-1401O demonstrated an ORR after 24 weeks of 69.6% among women who received the biosimilar in combination with a taxane compared with a 64% ORR for patients who took trastuzumab plus a taxane. The ratio of ORR for MYL-1401O to trastuzumab was 1.09—both 90% CI (0.974-1.211) and 95% CI (0.954-1.237). The difference in ORR between the 2 arms was 6.0% (90% CI, -1.3%-13.2%). At the week 48 cutoff, the median duration of response was 9.7 months in both groups.

Biosimilars are meant to foster competition and lower prices, and are defined as biological products that are "similar" or “interchangeable” with an FDA-licensed biological product, according to the US biosimilar pathway that was created under the Affordable Care Act.

von Minckwitz G, Ponomarova O, Morales S, et al. Efficacy and safety of biosimilar ABP 980 compared with trastuzumab in HER2-positive early breast cancer. In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract 151PD.