CDER-Approved BLA for ENHERTU® (fam-trastuzumab deruxtecan-nxki)
On December 20, 2019, the FDA granted accelerated approval to Daiichi Sankyo’s ENHERTU® (fam-trastuzumab deruxtecan-nxki) “for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer.” Of note: Daiichi Sankyo was granted Breakthrough Therapy, Fast Track, and Priority Review designations.
Key findings from the FDA’s Multi-Discipline Review:
The results of the phase 2 trial DS8201-A-U201 (NCT03248492; n=253) provided primary evidence of the effectiveness of fam-trastuzumab deruxtecan-nxki. The applicant submitted real-world evidence (RWE) and a literature-based analysis to support the demonstration of efficacy.
RWE: The applicant submitted RWE to serve as a matched historical cohort for DS8201-A-U201. The goal of the RWE was to establish a baseline for progression-free survival (PFS) and overall response rate (ORR).
Literature-based analysis: The applicant submitted a literature analysis to determine the reported efficacy of other treatments for HER2+ positive breast cancer.
What was done
RWE: The applicant utilized the Unicancer database to establish a matched cohort of 137 patients with HER2+ breast cancer to serve as comparable external controls. The ORR in this population was 12.2% (95% CI: 6.2, 18.2).
Literature-based analysis: For the literature analysis, the applicant reviewed 37 studies. The only inclusion criteria was whether patients had been previously treated with trastuzumab and chemotherapy. The literature review yielded an estimated ORR of 25.5% (95% prediction range: 17.1% to 36.1%).
When reviewing DS8201-A-U201, the FDA found a 60.3% ORR, which is “of sufficient magnitude to serve as a surrogate endpoint that improved over that of available therapies and is reasonably likely to predict clinical benefit.”
RWE: The FDA did not address the Unicancer data. The RWE is not included in the FDA label for fam-trastuzumab deruxtecan.
Literature-based analysis: The FDA did not address the literature-based analysis data. The literature-based analysis is not included in the FDA label for fam-trastuzumab deruxtecan.