Merck and Daiichi Sankyo’s withdrawal of an accelerated approval request for the antibody-drug conjugate ifinatamab deruxtecan is a “net positive” for rivals like GSK and Roche, according to RBC Capital Markets.
Merck and Daiichi Sankyo have voluntarily withdrawn an application seeking accelerated approval for the antibody-drug conjugate ifinatamab deruxtecan after the FDA found that the companies’ data package did not meet the criteria.
The pharma partners were proposing to use the ADC, also called I-DXd, for patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease had progressed on or after platinum-based chemotherapy. In regulatory discussions, the FDA indicated that the data supporting I-DXd’s submission “do not satisfy requirements needed to support an accelerated approval for the proposed indication,” according to a Friday news release.
“This is an incremental negative setback” for Merck, analysts at RBC Capital Markets told investors in a Sept. 27 note, contending that much of investors’ focus remains on the Kelun-Biotech-partnered TROP2-targeting ADC sacituzumab tirumotecan, being tested for non-small cell lung cancer.
Merck and Daiichi Sankyo continue to study I-DXd in a Phase 3 trial for ES-SCLC, which could be used for a future regulatory filing, Daiichi said in a statement. Enrollment is nearing completion for the study, according to Daiichi’s Abderrahmane Laadem, head of therapeutic area oncology development. BioSpace has reached out for more details.
“While we are disappointed that the current dataset are not supportive of an approval at this time, we are continuing to evaluate the role of ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer and other types of difficult-to-treat cancer,” Marjorie Green, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, said in a prepared statement.
I-DXd is also being tested in two other Phase 3 trials: IDeate-Prostate01 for metastatic castration-resistant prostate cancer and IDeate-Esophageal01 for advanced esophageal squamous cell carcinoma.
While not great news for Merck, I-DXd’s setback “is a net positive” for SCLC competitors GSK and Roche, RBC noted. GSK and Hansoh Pharma are developing the B7-H3 ADC risvutatug rezetecan (ris-rez), which during the recent World Conference on Lung Cancer (WCLC) achieved median overall survival (OS) of 18.5 months, versus 10.3 months in standard-of-care controls, according to a late-stage study conducted in China. Roche, meanwhile, is working with China’s MediLike Therapeutics on the ADC tambotatug pelitecan (tam-peli), which also demonstrated promising results at the WCLC, with a median OS of 13.3 months versus 9.4 months in comparators on standard of care in a Phase 3 study in China.
GSK expects to submit regulatory filings for ris-rez in 2028, while Roche plans to initiate global late-stage studies “quickly,” CMO Levi Garraway said earlier this month.
Merck and Daiichi Sankyo supported their accelerated approval application for I-DXd with data from the Phase 2 IDeate-Lung01 study, which last September demonstrated a 48.2% confirmed objective response rate in patients with ES-SCLC. In December, however, the FDA placed I-DXd’s late-stage development program in this indication on clinical hold after detecting a “higher than anticipated incidence” of interstitial lung disease leading to death in the Phase 3 IDeate-Lung02 trial. The regulator lifted the pause in January.
In more positive news, Merck on Friday reported the expanded approval of the HIF-2α therapy Welireg for advanced renal cell carcinoma with a clear cell component, indicated for patients who had undergone prior treatment with a PD-L1 blocker.
