Merck, Daiichi Withdraw I-DXd BLA in SCLC After FDA Flags Phase 2 Data

Daiichi Sankyo and Merck voluntarily withdrew the Biologics License Application for ifinatamab deruxtecan (I-DXd) in extensive-stage small cell lung cancer on September 25, after the FDA indicated the Phase 2 IDeate-Lung01 data “do not satisfy requirements needed to support an accelerated approval.” The withdrawal, announced at 4:30 pm EDT, kills the October 10 PDUFA date and the near-term path to market for the first-in-class B7-H3-directed antibody-drug conjugate. Merck closed at $148.78, up 0.5% on the day, with the news arriving after the close.

IDeate-Lung01 was a global, multicenter, randomized, open-label Phase 2 trial that enrolled 187 patients with previously treated ES-SCLC, using objective response rate by blinded independent central review as the primary endpoint. The single-arm dataset was not enough for the FDA. The program is not dead: the confirmatory IDeate-Lung02 Phase 3 trial, which pits I-DXd against physician’s-choice chemotherapy (amrubicin, lurbinectedin, or topotecan), is near-complete enrollment, and the IDeate-Prostate01 (castration-resistant prostate cancer) and IDeate-Esophageal01 (esophageal squamous cell carcinoma) Phase 3 trials remain ongoing.

This is the second Daiichi/Merck DXd ADC BLA withdrawn in about 16 months. Patritumab deruxtecan (HER3-DXd) was voluntarily withdrawn in May 2025 after its confirmatory HERTHENA-Lung02 trial missed overall survival. The pattern is now clear: the FDA is holding DXd ADC accelerated-approval filings to a randomized-data standard, and single-arm Phase 2 ORR is no longer enough to reach the market in these settings. For Merck, I-DXd in SCLC was a modest opportunity from the start, and our I-DXd PDUFA analysis pegged peak sales at $500 million to $1 billion against a $367 billion company. The read-through is broader: B7-H3 ADC development in SCLC now hinges on the Phase 3 readouts, not the accelerated-approval path.

What to watch next: the IDeate-Lung02 Phase 3 readout, which is now the binary event that decides whether I-DXd ever reaches the market in SCLC.

Source: Merck press release

What It Means for the Trade

The withdrawal removes the October 10 binary the wrong way — instead of a clean PDUFA decision, Merck and Daiichi holders now carry an open-ended wait for IDeate-Lung02. That Phase 3 trial is the only path back to an SCLC filing, and a trial that is merely near-complete enrollment still has to finish enrolling, run, and mature before any readout, which pushes the next hard SCLC catalyst well out. The market barely reacted — Merck closed up 0.5% — which tells you the PDUFA was never priced as a major catalyst. Our own peak-sales estimate of $500 million to $1 billion against a $367 billion company made this a rounding error for Merck; the trade was always in the read-through, not the label.

That read-through is the real story. The FDA has now twice rejected single-arm DXd ADC data, which resets the evidence bar for every accelerated-approval filing in solid tumors built on open-label Phase 2 response rates. If your thesis in any ADC name rested on an accelerated-approval shortcut, re-underwrite it against a randomized-data standard. Daiichi Sankyo bears more of the brunt — I-DXd was one of the closer-in assets in its oncology pipeline — while Merck remains a Keytruda story whose core thesis is untouched.

Mechanism and Pipeline Context

I-DXd is a B7-H3-directed ADC built on Daiichi’s DXd payload platform — the same linker-payload chemistry behind Enhertu and datopotamab deruxtecan. B7-H3 (CD276) is an immune-checkpoint molecule overexpressed on many solid tumors, including SCLC, prostate, and esophageal cancers, with limited expression on normal tissue, which is why multiple companies have B7-H3 programs in the clinic. The payload is a topoisomerase I inhibitor cleaved inside the tumor cell — the design that made Enhertu the class benchmark.

The Merck-Daiichi alliance now has three IDeate Phase 3 readouts ahead: Lung02 in SCLC, Prostate01 in castration-resistant prostate cancer, and Esophageal01 in esophageal squamous cell carcinoma. Prostate is arguably the bigger commercial prize, and none of the three retains an accelerated-approval lane after this withdrawal.

Risks and What Could Go Wrong

1. IDeate-Lung02 fails against physician’s-choice chemotherapy in a tough indication — a miss ends the SCLC opportunity entirely and adds a second program to the HER3-DXd withdrawal column.
2. The regulatory read-through is worse than the withdrawal itself — if the FDA is broadly tightening single-arm filings, every remaining catalyst in the DXd alliance gets a longer timeline and a higher bar.
3. Timeline drift — “near-complete enrollment” is not enrolled, and the data must mature before any readout.
4. Attention dilution — a Lung02 miss would refocus the market on execution risk across the whole alliance rather than the platform’s promise.