Theragenomic medicine: FDA approves Osimertinib (Tagrisso) to treat patients with non-small cell lung cancer (NSCLC) who carry the EGFR mutation T790M

Lung cancer is a huge problem; it is the leading cause of cancer death in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015,

according to the National Cancer Institute (NCI). The most common type of lung cancer, NSCLC occurs when cancer cells form in the tissues of the lung. The EGFR gene is a protein involved in the growth and spread of cancer cells.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in a statement that “the understanding of the molecular basis of lung cancer and reasons these cancers become resistant to prior treatments is rapidly evolving. Thus, the present 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 Osimertinib (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 Osimertinib (Tagrisso) is known to target. 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, Ph.D., 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 Osimertinib (Tagrisso) were demonstrated in two multicenter, single-arm studies involving a total of 411 patients with advanced EGFR T790M mutation-positive NSCLC whose disease worsened after treatment with an EGFR-blocking medication. In these two studies, 57 percent of patients in the first study and 61 percent of patients in the second study experienced a complete or partial reduction in their tumor size (known as objective response rate).

Osimertinib (Tagrisso) comes with a serious profile of adverse effects, as do almost all of the newest oncologic therapies of today. The most common side effects of Osimertinib (Tagrisso) are diarrhea, skin and nail conditions such as dry skin, rash and infection or redness around the fingernails. More serious side effects of Osimertinib (Tagrisso) include inflammation of the lungs and injury to the heart. Osimertinib (Tagrisso) also may cause harm to a developing fetus.

The importance and the expected therapy potential of Osimertinib (Tagrisso) for the eligible patients (i.e., T790M mutation positive) is illustrated by the fact that Osimertinib (Tagrisso) was granted breakthrough therapy designation, priority review and orphan drug designation. 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, in this particular case for patients whose tumors carry the T790M mutation. Moreover, Osimertinib (Tagrisso) was approved under the agency’s accelerated approval program, 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 program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.