Takeda therapy gets speedy FDA nod for lung cancers with rare genetic signature


Takeda Pharmaceutical’s cancer drug portfolio has added another FDA approved product, a targeted therapy that addresses tumors carrying a rare genetic signature.

The FDA approved the Takeda drug, mobocertinib, for adults whose non-small cell lung cancer has spread, either locally or to other parts of the body, after treatment with chemotherapy. The cancer must be characterized by an insertion mutation at exon 20 of epidermal growth factor receptor (EGFR), a protein involved in cell signaling. EGFR mutations contribute to the rapid cell growth of tumors.

Non-small cell lung cancer is the most common form of lung cancer, representing an estimated 85% of all new diagnosed cases annually. However, EGFR exon 20 insertion mutations are rare, comprising about 1% to 2% of cases. Currently available cancer drugs that target EGFR do not work against EGFR exon 20 insertion mutations.

The first drug that targets this mutation, Johnson & Johnson’s Rybrevant, secured the regulatory nod in May. But that bispecific antibody is given as an infusion. The Takeda drug is a small molecule that comes in capsule form, making it the first oral therapy for this particular genetic mutation. Takeda will market its new cancer drug under the name “Exkivity.”

FDA approval of Exkivity was based on the results of an open-label Phase 1/2 study that evaluated the Takeda drug in 114 patients whose cancer carried the EGFR exon 20 insertion mutation. Patients took the drug once daily. The main goal of the clinical trial was to measure overall response rate and the duration of the response.

The FDA said the overall response rate was 28%; the median duration of that response was 17.5 months. The results also showed that the overall survival of patients was a median of 24 months. Takeda had presented updated results from the study during the annual conference of the American Society of Clinical Oncology in May.

The most common adverse reactions reported in the study included diarrhea, rash, nausea, inflamed and sore mouth, and vomiting. The drug’s label carries a black box warning that alerts physicians and patients that the drug may cause a heart rhythm problem that could become fatal. Patients must be monitored for heart rhythm problems while they are taking the drug.

The EGFR exon 20 insertion mutation must be detected by a companion diagnostic. Alongside Exkivity’s regulatory nod, the FDA also approved a Thermo Fisher Scientific test that identifies the mutation.

Approval of the Takeda drug came sooner than expected. The FDA’s target date for a decision was Oct. 26. The decision was an accelerated approval based on less evidence than is typically required for a drug review. Such approvals require drug companies to conduct post-marketing studies to confirming efficacy, continuing to show that a drug’s benefit outweigh any safety risks.

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