AstraZeneca PLC Release: TAGRISSO (osimertinib) Receives U.S. FDA Full Approval

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Conversion from accelerated to full approval confirms the potential of TAGRISSO to become a standard of care for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer whose disease has progressed on or after EGFR-TKI therapy

Approval based on Phase III AURA3 trial that demonstrated significant improvement in progression-free survival with TAGRISSO as compared to chemotherapy

TAGRISSO demonstrated efficacy in patients with measurable central nervous system (CNS) lesions at baseline

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca today announced that the US Food and Drug Administration (FDA) has granted full approval for TAGRISSO® (osimertinib) 80mg once-daily tablets, for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after an EGFR tyrosine kinase inhibitor (TKI) therapy. TAGRISSO is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation, and efficacy data suggest it may be a new standard of care for these patients.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “By following the science, we aim to turn lung cancer into a chronic, manageable disease for patients and this milestone brings us one step closer to that ambition. The FDA’s full approval reinforces the potential of TAGRISSO to become the standard of care for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer whose disease has progressed on or after first-generation EGFR-TKI therapy.”

The full approval in the US is based on data from the randomized, Phase III AURA3 trial, in which TAGRISSO significantly improved progression-free survival (PFS) versus platinum-based doublet chemotherapy, providing 10.1 months of median PFS compared to 4.4 months from chemotherapy (hazard ratio 0.30; 70% risk reduction; 95% Confidence Interval [CI]: 0.23; 0.41; P<0.001). The results of this trial were recently presented at the 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria, and published in The New England Journal of Medicine.

Additionally, in a post-hoc subgroup analysis of patients with measurable central nervous system (CNS) lesions, TAGRISSO demonstrated an objective response rate (ORR) of 57% (95% CI: 37%; 75%) compared to 25% ORR from chemotherapy (95% CI: 7%; 52%). For CNS patients receiving TAGRISSO, median duration of response (DoR), defined as the time from the date of first documented response until progression or death event, was not yet reached at the time of analysis. Central nervous system metastases are typically difficult to treat, carry a very poor prognosis and affect up to 40% of patients with NSCLC.

In AURA3 the most common (>20%) adverse reactions observed in TAGRISSO-treated patients were diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%). Dose reductions occurred in 2.9% of patients treated with TAGRISSO. The most frequent adverse reactions that led to dose reductions or interruptions were prolongation of the QT interval as assessed by ECG (1.8%), neutropenia (1.1%), and diarrhea (1.1%). Serious adverse reactions were reported in 18% of patients treated with TAGRISSO and 26% of patients in the chemotherapy group. No single serious adverse reaction was reported in 2% or more patients treated with TAGRISSO.

H. Jack West, MD, Medical Oncology, Medical Director, Thoracic Oncology Program, Swedish Cancer Institute, said: “While most lung cancer specialists have already been very impressed with their earlier experience with osimertinib and embraced the opportunity to use it for T790M mutation-positive patients with acquired resistance to EGFR-TKI therapy, AURA3 provides even more compelling evidence. Here, we saw a striking efficacy benefit in favor of osimertinib over chemotherapy in T790M mutation-positive patients. Testing for EGFR T790M should be a critical next step in patients who develop acquired resistance after first-line EGFR TKI therapy.”

TAGRISSO was granted Fast Track, Breakthrough Therapy and Priority Review designations by the US FDA, and received Accelerated Approval for this indication in 2015 based on tumor response rate and duration of response. In September 2016, the FDA approved a blood-based companion diagnostic, representing the only FDA-approved and clinically-validated companion diagnostic test that uses a blood sample to confirm the presence of a T790M mutation. Blood-based testing is recommended only when a tumor biopsy cannot be obtained; if a patient tests negative for the T790M mutation with the blood-based test, their physician should re-evaluate the feasibility of tissue-based testing.

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 (eg, 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%)

INDICATION

TAGRISSO is indicated for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor therapy.

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 26% of all cancer deaths in the US, and more than breast, prostate and colorectal cancers combined. Among patients with non-small cell lung cancer (NSCLC), up to 40% have brain metastases at some time in the course of their disease. Patients who have EGFR mutation-positive NSCLC, which occurs in 10% to 15% of NSCLC patients in the US and Europe and 30% to 40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell signaling pathways that drive the growth of tumor cells. However, tumors almost always develop resistance to treatment, leading to disease progression. Approximately two-thirds of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the secondary mutation, T790M.

About TAGRISSO®(osimertinib)

TAGRISSO® (osimertinib) 40mg and 80mg once daily oral tablet has been approved in over 45 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced non-small cell lung cancer (NSCLC). Eligibility for treatment with TAGRISSO is dependent on confirmation that the EGFR T790M mutation is present in the tumor.

TAGRISSO is a third generation, irreversible EGFR tyrosine kinase inhibitor designed to inhibit both EGFR sensitizing and EGFR T790M resistance mutations and to have activity in the central nervous system (CNS). TAGRISSO is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.

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 six 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.

About AstraZeneca

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 main 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.

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