Takeda Pulls Lung Cancer Drug After Confirmatory Trial Misses Primary Endpoint

Pictured: Takeda office in Massachusetts/iStock, hapabapa

Pictured: Takeda office in Massachusetts/iStock, hapabapa

Takeda is voluntarily withdrawing its lung cancer drug mobocertinib, marketed as Exkivity, from U.S. and global markets after the drug failed to meet its primary endpoint in a confirmatory Phase III trial.

Based on those findings and following discussions with the FDA, Takeda intends to withdraw the drug from the U.S. market and “intends to similarly initiate voluntary withdrawal globally where Exkivity is approved,” Takeda said in a statement.

The company also noted it is “committed to ensuring patients receiving Exkivity can maintain access, as appropriate and in consultation with their healthcare provider” as it actively assesses “access mechanisms with regulatory authorities.”

The oral tyrosine kinase inhibitor was initially granted priority review by the FDA in April 2021 based on findings in a Phase I/II trial of patients with epidermal growth factor receptor (EGFR) Exon20 insertion mutation-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease had progressed after platinum-based chemotherapy. The study found an overall response rate of 28%, and a median overall survival of 24 months, and the drug was subsequently the only approved oral therapy for this type of mutation.

Non-small cell lung cancer is the most common form of lung cancer, accounting for about 85% of lung cancers diagnosed worldwide. But patients with EGFR Exon20 insertion mutations only account for 1% to 2% of NSCLC diagnoses, which carry a worse prognosis than other EGFR mutations.

The Exclaim-2 Trial was meant to confirm those initial results and the drug’s approval as a second-line treatment, as well as extend the label for the drug into the first-line setting as a potential alternative to platinum-based chemotherapy. Takeda previously projected peak revenues as high as $600 million if the drug received first-line approval.

In the meantime, Takeda will “continue to assess the impact of the withdrawal and update our full-year, consolidated forecast for the fiscal year,” according to the company’s announcement “as appropriate and necessary.”

Awny Farajallah, head of global medical affairs oncology at Takeda, added in a statement  that “we have been fortunate to witness the impact Exkivity has had on this previously underserved population and are encouraged to see the advancements made since its approval to introduce new therapies for these patients.” Farajallah added that the company hopes that “findings from the EXCLAIM-2 study will inform future research and development for this disease.”

It’s not the only disappointment recently for the Japanese pharma.

The company’s investigational enzyme replacement therapy TAK-611 also failed to meet both primary and secondary endpoints in a recent Phase II study. Andy Plump, Takeda’s president of R&D, noted that the results mean the drug program “is likely to be discontinued.” The candidate was being developed for metachromatic leukodystrophy (MLD), a rare genetic lysosomal storage disease characterized by a pathogenic build-up of lipids in cells—particularly in the nervous system, which lead to the progressive loss of organ function.

Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at lynchjourno@gmail.com.

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