Dive Brief:

• Merck & Co. and Daiichi Sankyo have withdrawn a U.S. approval application for an experimental lung cancer drug in a setback that erases an edge the companies had on multiple rivals.
• Merck and Daiichi had sought an “accelerated” approval for the drug, ifinatamab deruxtecan, or “I-DXd,” in extensive-stage small-cell lung cancer based on response rates to treatment in Phase 2 testing. A decision was expected by Oct. 10. But the Food and Drug Administration indicated those findings aren’t sufficient to warrant such a clearance in that indication, leading the companies to pull their request. 
• I-DXd is currently being evaluated against chemotherapy in a late-stage trial in patients with relapsed disease. Results from that study, if positive, could support a traditional approval request. But Merck and Daiichi have reported a setback in that trial, too, as recruitment was temporarily halted late last year when a “higher than anticipated” number of deaths from a serious lung condition was observed among treatment recipients. 

Dive Insight:

Merck is bracing for the day next decade when Keytruda, its top moneymaker, loses patent protection. The company is leaning on many different emerging therapies to offset the coming losses, and antibody-drug conjugates — a popular kind of precision cancer medicine — are one key area of focus. 

Over the last several years, the company has struck deals with Daiichi Sankyo and Kelun-Biotech to obtain multiple ADCs that are now in advanced testing. One called sac-TMT, for instance, is now seen by Merck executives as a future “cornerstone” therapy and is involved in 17 global trials. I-DXd is in the mix, too, though Wall Street’s expectations have cooled as competing programs have progressed. 

I-DXd targets a protein called B7-H3 that’s overexpressed in small-cell lung cancer, a particularly aggressive lung tumor with a poor prognosis. At a recent medical meeting, this kind of approach was prominently featured as potentially changing care in patients whose disease is “extensive,” or has spread to both lungs or other parts of the body. In Phase 3 studies run in China, two prospects recently licensed to Roche and GSK, respectively, showed the potential to substantially outperform chemotherapy — without, so far, the level of interstitial lung disease, a potentially deadly form of lung inflammation, observed in testing of I-DXd. 

GSK has already begun global testing of its B7-H3 drug, “riz-rez.” Roche could soon follow with its prospect, “tam-peli.” The progress of both of those medicines, combined with I-DXd’s previous setbacks, have left investors ascribing very little value to Merck’s drug, wrote RBC Capital Markets analyst Trung Huynh. 

“We came away from [those recent presentations] believing that both riz-rez and tam-peli had a better safety profile than I-DXd,” Huynh wrote.

An accelerated approval could have given Merck an edge on its rivals. But the FDA’s decision stance isn’t “entirely unsurprising” given the “limited” results underlying the submission and the “increased scrutiny” the agency has been applying in such cases, Huynh wrote. With the application now pulled, GSK has a roughly two month lead on Merck in SCLC, he added. 

Merck and Daiichi’s decision also suggests the “bar for demonstrating a meaningful advantage” in SCLC “may have risen” following the clearance of Amgen’s Imdelltra, wrote Cantor Fitzgerald’s Li Watsek.  

Zai Lab and Ideaya Biosciences, the developers of two different kinds of ADCs for SCLC in advanced testing, could benefit, Watsek added. Zai Lab’s “zoci” is in pivotal testing and could become the first ADC approved for the condition, while Ideaya’s may begin a late-stage trial by the end of 2026.

Outside of lung cancer, Merck and Daiichi are also testing I-DXd in two other Phase 3 trials in prostate cancer and esophageal squamous cell carcinoma.