AstraZeneca pitches Tagrisso for new application in Japan

AstraZeneca announced the submission of a supplemental new drug application (sNDA) to Japan's Pharmaceuticals and Medical Devices Agency for the use of Tagrisso (osimertinib), a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with clinical activity against central nervous system (CNS) metastases, on Monday.

The FTSE 100 firm said the application was for the first line treatment of patients with inoperable or recurrent EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC).

It said the Japan sNDA was based on data from the Phase III FLAURA trial, in which Tagrisso “significantly improved” progression-free survival compared to current first-line EGFR-TKIs, erlotinib or gefitinib, in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC.

“Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-quarter of all cancer deaths, more than breast, prostate and colorectal cancers combined,” AstraZeneca’s board explained in its statement.

“Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.

“These patients are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell-signalling pathways that drive the growth of tumour cells.”

However, tumours almost always developed resistance to EGFR-TKI treatment, AstraZeneca explained, leading to disease progression, with approximately half of patients developing resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the resistance mutation, EGFR T790M.

“Tagrisso also targets this secondary mutation that leads to disease progression.

“There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFR-mutated NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.”

AstraZeneca described Tagrisso as a “third-generation, irreversible” EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases.

Tagrisso 40mg and 80mg once-daily oral tablets had been approved in more than 60 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC.

It was also being investigated in the adjuvant setting and in combination with other treatments.

“The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg once daily vs standard-of-care EGFR-TKIs in previously-untreated patients with locally-advanced or metastatic EGFR-mutated NSCLC.

“The trial was a double-blinded, randomised trial, with 556 patients across 29 countries.”