Merck & Co. and Daiichi Sankyo have withdrawn their U.S. application for accelerated approval of the experimental antibody-drug conjugate ifinatamab deruxtecan (I-DXd) in extensive-stage small-cell lung cancer. The Food and Drug Administration indicated that response rates from Phase 2 testing were not sufficient to support clearance in that indication, according to BioPharma Dive. A decision had been expected by Oct. 10.
The withdrawal removes a potential first-mover advantage for Merck and Daiichi in a competitive area. I-DXd targets B7-H3, a protein overexpressed in small-cell lung cancer. At a recent medical meeting, B7-H3-directed therapies were highlighted as potentially practice-changing for extensive-stage disease. However, two similar drugs developed in China and licensed to Roche and GSK have shown strong Phase 3 results without the same level of interstitial lung disease seen with I-DXd. GSK has already begun global testing of its drug, riz-rez, and now holds roughly a two-month lead over Merck in this setting, according to RBC Capital Markets analyst Trung Huynh.
I-DXd is still being evaluated against chemotherapy in a late-stage trial for relapsed disease, and in Phase 3 trials for prostate cancer and esophageal squamous cell carcinoma. Recruitment in the relapsed-disease trial was temporarily halted late last year after a higher-than-anticipated number of deaths from a serious lung condition occurred among treatment recipients. Analysts noted that the FDA's decision was not entirely surprising given the limited data and increased regulatory scrutiny, and that the bar for showing a meaningful advantage in small-cell lung cancer may have risen after the approval of Amgen's Imdelltra.