FDA Rejects Amgen's Trastuzumab Biosimilar, ABP 980

Amgen has announced that the FDA has issued a Complete Response Letter (CRL) for its biosimilar trastuzumab candidate, ABP 980. In a brief statement on its website, Amgen said that it would work closely with the FDA on the product, and that it did not expect the CRL to impact its US launch plans. Amgen and its partner, Allergan, submitted their Biologics License Application for the drug in August 2017.

Amgen previously released complete phase 3 results from a study in patients with HER2-positve early breast cancer at the 2017 annual meeting of the European Society for Medical Oncology in Madrid, Spain. The study compared the proposed biosimilar with the reference Herceptin, and the primary endpoints were risk differences (RD) and risk ratio (RR) of pathologic complete response (pCR).

By local review, the primary pCR endpoint was achieved in 48.0% of patients in the ABP 980 arm versus 40.5% of those in the reference trastuzumab arm. The advantage for the biosimilar exceeded the prespecified 13% margin for bioequivalence by RD. While the lower boundary of the 95% confidence interval (CI) for RD exceeded 0% (1.2%), the upper boundary surpassed 13% (13.4%), which met the criterion of a significant advantage. The RR on local review analysis showed the same result. However, the prespecified margins were not exceeded in the central review.

The safety profile of ABP 980 was also similar to that of the reference product; when adverse events were compared collectively and individually, the rates were similar for ABP 980 and reference trastuzumab over the course of neoadjuvant treatment.

Despite today’s US regulatory setback, the drug was, on May 30, 2018, listed on the European Medicines Agency’s (EMA) website as having achieved the European Commission’s authorization on May 16, 2018 for marketing under the brand name Kanjinti. The biosimilar is approved in the indications of early breast cancer, metastatic breast cancer, and metastatic gastric cancer. The drug received a positive opinion from the EMA’s Committee for Medicinal Products for Human Use in March 2018.