The Japanese pharma had one asset rejected by the FDA and withdrew a regulatory application for another, but already this month the company has secured an approval for AstraZeneca-partnered Dato-DXd, to be marketed as Datroway.
Daiichi Sankyo is growing rapidly thanks to AstraZeneca-partnered breast cancer med Enhertu, with revenue of just under $4 billion expected for 2024. But U.S. chief executive Ken Keller is pretty upfront that 2024 didn’t exactly go as planned.
It was “not a perfect year,” he told BioSpace on the sidelines of the J.P. Morgan Healthcare Conference. That’s because, while Enhertu flourished, the Japanese pharma received a complete response letter for patritumab deruxtecan (HER3-DXd) and withdrew an application for up-and-coming antibody drug conjugate datopotamab deruxtecan, or Dato-DXd, in non-small cell lung cancer (NSCLC).
So, all in all, a “good year, not perfect last year,” said Keller, who serves as CEO of Daiichi Sankyo, Inc., the U.S. subsidiary of the global pharmaceutical company, and as head of the Global Oncology Business.
But 2025 is starting off with a bang. Dato-DXd has now been approved for its first indication—for the treatment of patients with unresectable or metastatic breast cancer who are HR-positive and HER2-negative. The AstraZeneca-partnered drug will be marketed as Datroway. BioSpace sat down with Keller prior to the FDA approval, but his enthusiasm for what’s to come was clear.
“I’ve never been able to say, ‘We’ve got eight top line readouts for registration trials’ at any company I’ve been at,” Keller said. “So I think it could be a really special year.”
Learning From Mistakes
But first, it’s important to look at how Daiichi got to this point, because the stumbles of 2024 will define 2025. On the withdrawal, Keller explained that Daiichi and AstraZeneca chose to walk back an application for Dato-DXd in patients with metastatic NSCLC who did not have genomic alterations, with non-squamous disease. Trials had demonstrated that the ADC achieved two-month progression-free survival and a “non-significant” trend in overall survival, Keller explained. After talking with the FDA, it became clear “that wasn’t going to be enough,” he said.
Daiichi pulled the application and refiled it in a smaller population for patients with EGFR-mutated NSCLC. The FDA granted a priority review and set a decision date in July. Keller said that while the population is smaller in the U.S. and Europe, there are actually more patients in China and Japan with EGFR-mutated disease.
“It’s going to be a big, important drug there,” he said. “A key thing we learned is that Dato-DXd may require us to be smarter in selecting the patients that it will benefit.” The company is working on digital biomarker pathology to further break down which patients may benefit.
As for the complete response letter for HER3-DXd, Daiichi and partner Merck had been seeking an accelerated approval of the drug for patients with locally advanced or metastatic EGFR-mutated NSCLC who had already received two or more other therapies. The FDA rejected the application due to manufacturing concerns. Keller could not provide an update on the process to address the concerns flagged by the FDA.
Looking into 2025, Keller said Daiichi is expecting top line readouts for eight registrational trials across its ADC portfolio, including five new indications for Enhertu and two for Dato-DXd: the EGFR-mutated NSCLC group plus a trial in triple negative breast cancer.
Another prospect with clinical milestones this year is ifinatamab deruxtecan (I-DXd). Partner Merck acquired Harpoon Therapeutics a year ago and offered Daiichi the chance to participate through their existing deal. The amendment added an upfront payment of $170 million for Merck to provide access to the delta-like ligand 3 (DLL3) targeting T cell engager MK-6070. That drug will now be combined with I-DXd in clinical trials for small cell lung cancer (SCLC).
Early data from I-DXd in this indication showed a 52% overall response rate, Keller said. A registrational trial will read out this year.
2025 will also see Daiichi working hard on the Datroway launch. Keller said the company is actually going to be competing against itself in the initial breast cancer indication, as Enhertu has the nod here as well. Gilead’s Trodelvy is also approved for this population. Keller said that Datroway has an every-three-week infusion schedule compared to every two weeks for Trodelvy.
“I think the efficacy looks similar right now, and we’ll have to see,” Keller said. Regarding safety, he said the data for Datroway show fewer grade 3 adverse events than Gilead’s offering.
Moving as Fast as Cancer
Keller said that Daiichi’s key to staying on top of the ADC world is to do more clinical trials as fast as possible. He has seen the frenzy of interest, with Big Pharmas swallowing up ADC-focused biotechs, licensing assets from China and new companies launching. Daiichi has even been a participant, partnering with Merck in a mega-licensing deal in 2023 worth a potential $22 billion.
“There’s been over $100 billion in M&A in the ADC space over the last three or four years. It’s really remarkable,” Keller said. “I don’t see any big new acquisitions, because there’s nobody left that is big. But I think the science in ADCs continues to move very, very quickly.”
ADCs have three components: an antibody, linker and payload. Companies have been tinkering with that formula to create even more efficacious candidates. Keller said the industry has shifted to second generation payloads. Daiichi is looking at bispecifics in ADCs, meaning offering two different payloads to tackle the cancer from multiple angles.
“It’s just the beginning of the science,” Keller said. “Unfortunately, cancer is smart. It evolves.” Even Daiichi’s best offerings will someday be outsmarted by cancer and new options will be needed, he added. “There will be resistance, and when resistance occurs, you’ll need different ADCs.”
Daiichi itself is evolving, too. When the deal with AstraZeneca was signed in 2020, the Japanese company was just entering oncology. The partnership produced Enhertu and now Datroway. Then Merck signed on for a handful of assets.
Keller said that Daiichi now has the ability to go it alone if the asset fits. “The bar for doing another partnership gets higher and higher, because since we started this five, six years ago with the [AstraZeneca] alliance, today, we’ve got a full team of people across the globe. So I think the bar does get pretty high.”
