An accelerated approval for a potential growth driver for Takeda is in danger.
Targeted non-small cell lung cancer drug Exkivity has failed in a phase 3 trial in newly diagnosed patients, and the study has stopped early, Takeda said Thursday in its quarterly earnings report.
Takeda's R&D chief, Andy Plump, informed investors during a call that the company is in discussions with regulators regarding the data and will determine the next steps.
News of Exkivity’s EXCLAIM-2 trial flop comes just a few days after Johnson & Johnson said its rival drug Rybrevant has succeeded at delaying cancer progression in first-line NSCLC patients. Both drugs used tumor shrinkage data from single-arm trials to win FDA accelerated approvals in 2021 as second-line treatments for NSCLC with EGFR exon20 insertion mutations.
As part of Exkivity’s accelerated approval, the FDA required progression-free survival data from a randomized trial to verify the drug’s clinical benefit. Since then, EXCLAIM-2 has been the only phase 3 of Exkivity listed by Takeda.
A Takeda spokesperson confirmed to Fierce Pharma that EXCLAIM-2 serves as a confirmatory trial for Exkivity’s accelerated approval.
“We are continuing to evaluate the full data set to gain a greater understanding of the findings,” the spokesperson said, declining to comment further on ongoing regulatory proceedings.
Failure of the trial now puts Exkivity’s go-ahead in danger, especially given that the FDA’s oncology department has lately tightened the rope on accelerated approval regulations. At the request of the FDA, GSK recently pulled multiple myeloma therapy Blenrep off the U.S. market, just 15 days after announcing a confirmatory trial failure.
The FDA has in the past also kept accelerated approvals intact despite confirmatory trial flops because of unmet medical needs. But given J&J’s phase 3 win and Rybrevant’s availability in the same disease area, it would be hard for Takeda to use that argument.
Takeda designed EXCLAIM-2 differently from Rybrevant’s PAPILLON trial. The Japanese pharma tested Exkivity as a single agent in the front-line setting, whereas J&J combined Rybrevant with chemotherapy.
Exkivity is one of two growth and launch products in Takeda’s oncology portfolio, alongside ALK lung cancer med Alunbrig. The company has projected $300 million to $600 million in peak sales for Exkivity. In the 12 months ended in March, the EGFR inhibitor pulled in 3.7 billion Japanese yen ($26 million) in sales. And Takeda has said that Exkivity and Rybrevant were splitting the second-line market 50-50.
Takeda may have another cancer drug growth driver soon. The company recently paid $400 million upfront to in-license Hutchmed’s VEGFR inhibitor fruquintinib, which is approved in China under the brand name Elunate. In May, the FDA placed fruquinitib's application for previously treated metastatic colorectal cancer under priority review, with a decision set for Nov. 30.
Takeda didn’t always have the best of luck with the FDA. The drugmaker a few days ago decided to withdraw its application for dengue vaccine TAK-003, also known as Qdenga, after the FDA required more data that weren’t captured by a phase 3 trial.