FDA Approves Osimertinib to Treat Patients With EGFR T790M Positive Advanced NSCLC After Progression to Other EGFR Tyrosine Kinase Inhibitors

FDA also approved the first companion diagnostic test to detect the EGFR resistance mutation that osimertinib targets

On 13 November, 2015, the US Food and Drug Administration granted accelerated approval for an oral medication to treat patients with advanced non-small cell lung cancer (NSCLC). Osimertinib (Tagrisso), formerly known as AZD9291 is now approved for patients whose tumours express epidermal growth factor receptor (EGFR) mutation (T790M) and whose disease has progressed after treatment with other EGFR tyrosine kinase inhibitors.

Dr Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said: “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 patients who were treated.” 

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

“The approval of safe and effective companion diagnostic tests and drugs continue to be important developments in oncology,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “The availability of the cobas EGFR Mutation Test v2 meets a need for the detection of this important EGFR gene mutation, which can alter treatment effectiveness.”

The safety and efficacy of Tagrisso were demonstrated in two multicenter, single-arm studies involving a total of 411 patients with advanced EGFR T790M mutation-positive NSCLC whose disease progressed after treatment with an EGFR inhibitor. In these two studies, 57% of patients in the first study and 61% of patients in the second study experienced objective response rate.

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

In a combined analysis of the 411 patients in both trials, the FDA reported that the most commonly reported all-grade adverse events were diarrhoea, rash, dry skin, nail toxicity, eye disorders, nausea, decreased appetite, and constipation. These events were primary grade 1/2, with a low rate of grade ≥3 adverse events. The most common grade ≥3 adverse events were pneumonia and pulmonary embolism. It also may cause harm to a developing foetus.

The FDA granted Astra Zeneca breakthrough therapy designation, priority review and orphan drug designation for Tagrisso. 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 designation 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.

Tagrisso was approved under the agency’s accelerated approval programme, which allows the approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This programme provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.

Tagrisso is marketed by Astra Zeneca Pharmaceuticals based in Wilmington, Delaware.

The cobas EGFR Mutation Test v2 is marketed by Roche Molecular Systems of Pleasanton, California.