US FDA Accepts Regulatory Submission for TAGRISSO (Osimertinib) in 1st-Line EGFR-Mutated Non-Small Cell Lung Cancer
TAGRISSO granted Priority Review; acceptance follows FDA’s Breakthrough Therapy Designation
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca today announced that the US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) 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, in the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR mutations (exon 19 deletions or exon 21 (L858R) substitution mutations). The FDA has granted TAGRISSO Priority Review status, and previously granted Breakthrough Therapy Designation for TAGRISSO in the 1st-line treatment of patients with metastatic EGFR mutation-positive (EGFRm) NSCLC.
The submission acceptance is based on data from the Phase III FLAURA trial, in which TAGRISSO significantly improved progression-free survival (PFS) compared to current 1st-line EGFR-TKIs, erlotinib or gefitinib, in previously-untreated patients with locally advanced or metastatic EGFRm NSCLC.
Detailed results of the FLAURA trial can be found in the New England Journal of Medicine, published November 18, 2017.
On September 28, 2017, the US NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) were updated to include the use of TAGRISSO in the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC. The use of TAGRISSO in this indication is not yet approved by the FDA.
TAGRISSO once-daily tablets are approved by the FDA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after an EGFR TKI therapy.
TAGRISSO® (osimertinib) Important Safety Information
- There are no contraindications for TAGRISSO
- Interstitial Lung Disease (ILD)/Pneumonitis occurred in 3.5% and was fatal in 0.6% of 833 TAGRISSO-treated patients. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD is confirmed
- Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 833 TAGRISSO-treated patients, 0.7% of patients were found to have a QTc > 500 msec, and 2.9% of patients had an increase from baseline QTc > 60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
- Cardiomyopathy occurred in 1.9% and was fatal in 0.1% of 833 TAGRISSO-treated patients. Left Ventricular Ejection Fraction (LVEF) decline ≥ 10% and a drop to < 50% occurred in 4% of 655 TAGRISSO-treated patients. Conduct cardiac monitoring, including an assessment of LVEF at baseline and during treatment in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure or persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks, permanently discontinue TAGRISSO
- Keratitis was reported in 0.7% of 833 TAGRISSO-treated patients in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye) to an ophthalmologist
- Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during TAGRISSO treatment and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
- The most common adverse reactions (≥20%) in patients treated with TAGRISSO were diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%)
Please see complete Prescribing Information including Patient Information.
NOTES TO EDITORS
About Non-Small Cell Lung Cancer (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. Approximately 7% to 23% in Western populations and 30% to 50% of patients in Asian populations have tumors that contain activating mutations in epidermal growth factor receptor (EGFR). These patients are particularly sensitive to treatment with currently available EGFR tyrosine kinase inhibitors (TKIs), which block the cell-signaling pathways that drive the growth of tumor cells. However, tumors almost always develop resistance to EGFR-TKI treatment, leading to disease progression. Approximately half of patients develop 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 central nervous system efficacy, since approximately 25% of patients with EGFR-mutated NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.
About TAGRISSO® (osimertinib)
TAGRISSO® (osimertinib) is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) designed to inhibit both EGFR sensitizing and EGFR T790M resistance mutations, with clinical activity against central nervous system (CNS) metastases. TAGRISSO 40mg and 80mg once-daily oral tablets have been approved in more than 60 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced non-small cell lung cancer.
TAGRISSO is also being investigated in the adjuvant setting and in combination with other treatments.
About the FLAURA trial
The FLAURA trial assessed the efficacy and safety of osimertinib 80mg once daily vs standard-of-care epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer. The trial was a double-blinded, randomized trial, with 556 patients across 29 countries.
About AstraZeneca in Lung Cancer
AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have two approved medicines and a growing pipeline that targets genetic changes in tumor cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
US-15760 Last Updated 12/17
Michele Meixell, +1-302-885-2677
Abby Bozarth, +1-302-885-2677
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