Merck and Daiichi Sankyo Withdraw Accelerated Approval Application for Lung Cancer ADC

Merck (MSD) of the United States and Japan’s Daiichi Sankyo have withdrawn their application for accelerated approval of an antibody-drug conjugate (ADC) candidate for lung cancer.

According to BioPharma Dive on the 27th (local time), the companies voluntarily withdrew their application to the U.S. Food and Drug Administration (FDA) for ifinatamab deruxtecan (I-DXd), a treatment for small cell lung cancer.

The companies sought accelerated approval for extensive-stage small cell lung cancer based on the response rate in a phase 2 trial, and the FDA was expected to make a decision by Oct. 10. However, the companies withdrew the application after the FDA said there was insufficient evidence to support approval for the indication.

I-DXd is also being studied in a late-stage trial comparing it with chemotherapy in patients whose cancer has relapsed. Enrollment in that trial was temporarily paused late last year after more treatment-arm deaths related to severe lung disease than expected were observed.

I-DXd targets B7-H3, a protein overexpressed in small cell lung cancer. At recent medical meetings, this approach has drawn attention as a potential way to change treatment for patients with extensive-stage disease.

In phase 3 trials conducted in China, two candidates licensed to Roche and GSK, respectively, substantially outperformed chemotherapy. Neither drug has yet shown adverse effects at the level of interstitial lung disease observed in the I-DXd trial.

GSK has already started a global trial of its B7-H3 drug, ris-rez, and Roche is expected to follow with tam-peli. RBC Capital Markets analyst Trung Huynh wrote, “We believe both ris-rez and tam-peli have better safety profiles than I-DXd.”

Huynh said Merck could have gained an advantage over competitors if accelerated approval had been granted, but called the decision “not at all surprising,” given the limited evidence submitted and the FDA’s heightened scrutiny. He added that the withdrawal puts GSK about two months ahead of Merck in small cell lung cancer.

Cantor Fitzgerald analyst Lee Whatsek said the bar for demonstrating “meaningful benefit may have risen” in small cell lung cancer following Amgen’s approval of Imdelltra.

Zai Lab and IDEAYA Biosciences could also benefit, Whatsek added. Zai Lab’s zoshi is in confirmatory trials and could become the first ADC approved for this indication, while IDEAYA’s candidate could enter late-stage trials by the end of 2026.

Beyond lung cancer, Merck and Daiichi Sankyo are separately conducting two phase 3 trials of I-DXd in prostate cancer and esophageal squamous cell carcinoma.