Merck & Co. and Daiichi Sankyo have withdrawn their U.S. accelerated approval application for the lung cancer drug ifinatamab deruxtecan (I-DXd) after the FDA deemed Phase 2 response rates insufficient. This setback erases the companies' head start against rivals like GSK and Roche, who are developing competing B7-H3 targeting therapies with potentially better safety profiles. The decision comes amid historical safety concerns for I-DXd, including a temporary trial halt in late 2025 due to patient deaths from a serious lung condition.
Withdrawal of the FDA application
- ▪Merck & Co. and Daiichi Sankyo withdrew their U.S. accelerated approval application for the experimental lung cancer drug ifinatamab deruxtecan (I-DXd) on or before September 28, 2026
- ▪Merck & Co. and Daiichi Sankyo had expected an FDA decision on the accelerated approval application for ifinatamab deruxtecan (I-DXd) in extensive-stage small-cell lung cancer by October 10, 2026
- ▪The Food and Drug Administration indicated that Phase 2 testing response rates for ifinatamab deruxtecan (I-DXd) were not sufficient to warrant accelerated approval in extensive-stage small-cell lung cancer
Late-stage trial of ifinatamab deruxtecan
- ▪Recruitment for the late-stage trial of ifinatamab deruxtecan (I-DXd) against chemotherapy in relapsed small-cell lung cancer was temporarily halted in late 2025 due to a higher than anticipated number of deaths from a serious lung condition
- ▪Ifinatamab deruxtecan (I-DXd) is being evaluated against chemotherapy in a late-stage trial in patients with relapsed small-cell lung cancer disease, which could support a traditional approval request
Competing B7-H3 antibody-drug conjugates
- ▪Two B7-H3 targeting antibody-drug conjugates, tam-peli and riz-rez, licensed to Roche and GSK, respectively, showed potential to outperform chemotherapy in Phase 3 studies run in China
- ▪GSK has begun global testing of its B7-H3 drug 'riz-rez,' while Roche could soon follow with its prospect 'tam-peli.'
- ▪The B7-H3 targeting prospects, tam-peli and riz-rez, licensed to Roche and GSK, have not shown the level of interstitial lung disease, a potentially deadly lung inflammation, observed in testing of ifinatamab deruxtecan (I-DXd)
- ▪GSK has a roughly two-month lead on Merck & Co. in small-cell lung cancer following the withdrawal of the accelerated approval application for ifinatamab deruxtecan (I-DXd)
Merck's antibody-drug conjugate strategy
- ▪Merck & Co. has struck deals with Daiichi Sankyo and Kelun-Biotech over the last several years to obtain multiple antibody-drug conjugates in advanced testing
- ▪Merck & Co. executives view the antibody-drug conjugate sac-TMT as a future cornerstone therapy, which is currently involved in 17 global trials
- ▪Merck & Co. is leaning on emerging therapies, including antibody-drug conjugates, to offset coming losses when its top moneymaker, Keytruda, loses patent protection next decade
Debatable claims
- ▪The FDA was justified in rejecting Merck's accelerated approval bid for its lung cancer drug
- ▪Merck's lung cancer drug poses unacceptable safety risks to patients
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