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The Food and Drug Administration has granted accelerated approval to Tagrisso (osimertinib) for the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors have the specific epidermal growth factor receptor mutation T790M, and whose disease has worsened after treatment with other EGFR-blocking therapy. Tagrisso is an oral tyrosine kinase inhibitor that inhibits TKI-resistance T790M mutations.

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"Our understanding of the molecular basis of lung cancer and the reasons these cancers become resistant to prior treatments is rapidly evolving," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release.


"This approval provides a new treatment for patients who test positive for the EGFR resistance mutation, T790M, and is based on substantial evidence from clinical trials that shows Tagrisso had a significant effect on reducing tumor size in over half of the patients who were treated."


The accelerated approval program, under which Tagrisso was approved, allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.


Tagrisso was also granted Breakthrough Therapy, Priority Review, and Orphan Drug designations. The Breakthrough Therapy designation is granted for a drug that is intended to treat a serious condition when, at the time an application is submitted, preliminary clinical evidence indicates that a drug may demonstrate substantial improvement over available therapies.


Priority Review is granted to drug applications that show a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan Drug designation provides incentives such as tax credits, user fee waivers, and eligibility for market exclusivity to assist and encourage the development of drugs for rare diseases.


Safety and Effectiveness

The safety and effectiveness of Tagrisso were demonstrated in two multicenter, single-arm studies involving 411 patients in total with advanced EGFR T790M mutation-positive NSCLC whose disease had worsened after treatment with an EGFR-blocking medication. Fifty-seven percent of the patients in the first study and 61 percent in the second study experienced a complete or partial reduction in their tumor size after receiving the agent.


Continued approval for this indication may be contingent upon further confirmatory studies.


The most common side effects of Tagrisso are diarrhea and skin and nail conditions, such as dry skin, rash and infection or redness around the fingernails. Serious side effects of the drug include inflammation of the lungs and injury to the heart. It also may cause harm to a developing fetus.


Companion Diagnostic

The FDA also approved the first companion diagnostic test (cobas EGFR Mutation Test v2) to detect the type of EGFR resistance mutation that Tagrisso is known to target. The newly approved version of the test (v2) adds the T790M mutation to the clinically relevant mutations detected by the original cobas EGFR Mutation Test (v1).


The test now identifies 42 EGFR mutations in exons 18 through 21, including L858R, exon 19 deletions, and T790M. The test is performed on the cobas 4800 System, which offers high-performance amplification and detection coupled with software that automates results interpretation and reporting.


Tagrisso is marketed by Astra Zeneca Pharmaceuticals, and the cobas EGFR Mutation Test v2 is marketed by Roche Molecular Systems.