TAGRISSO® (osimertinib) Granted Breakthrough Therapy Designation by US FDA for the 1st-Line Treatment of Patients with EGFR
Mutation-Positive Non-Small Cell Lung Cancer
Designation based on positive Phase III FLAURA trial results
Sixth Breakthrough Therapy Designation for an AstraZeneca New Oncology medicine
AstraZeneca today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD)
for TAGRISSO® (osimertinib) for the 1st-line treatment of patients with metastatic epidermal growth factor receptor
(EGFR) mutation-positive non-small cell lung cancer (NSCLC).
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The
Breakthrough Designation acknowledges not only TAGRISSO’s potential as a 1st-line standard of care in advanced EGFR
mutation-positive NSCLC, but also the significant need for improved clinical outcomes in this disease. The results of the FLAURA
trial have the potential to redefine clinical expectations and offer new hope for patients who currently have a poor
prognosis.”
The FDA granted the BTD based on data from the Phase III FLAURA trial of osimertinib versus standard-of-care EGFR tyrosine
kinase inhibitor (TKI) therapy in previously-untreated patients with locally-advanced or metastatic EGFR mutation-positive NSCLC.
In the trial, median progression-free survival was 18.9 months for osimertinib compared with 10.2 months for
EGFR-TKIs (erlotinib or gefitinib). Improvements were seen in all pre-specified subgroups, including patients with and without
brain metastases.
In the FLAURA trial, the safety profile of osimertinib was consistent with previous experience. In patients treated with
osimertinib, the most common AEs were diarrhea (58%, any grade [2% Grade ≥3]) and dry skin (32%, any grade [<1% Grade ≥3]), and
in the comparator arm group the most common AEs were diarrhea (57%, any grade [2% Grade ≥3]) and dermatitis acneiform (48%, any
grade [5% Grade ≥3]). Of the patients on osimertinib, 34% had a Grade ≥3 AE, compared to 45% in the comparator arm, and 13% of
patients on osimertinib had an AE leading to treatment discontinuation compared to 18% in the comparator arm.
On September 28, 2017, the US NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) were updated to
include the use of osimertinib in the 1st-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive
NSCLC. The use of osimertinib for the first-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive
NSCLC is not yet FDA approved.
TAGRISSO is currently approved in more than 50 countries, including the US, EU, Japan and China, as 2nd-line treatment for
patients with advanced NSCLC who progress following treatment with an EGFR-TKI due to the EGFR T790M resistance mutation. 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 is the first and only
approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation.
This is the sixth BTD that AstraZeneca has received from the FDA for an oncology medicine since 2014. BTD is designed to
expedite the development and regulatory review of new medicines that are intended to treat a serious condition and that have shown
encouraging early clinical results, which demonstrate substantial improvement on a clinically- significant endpoint over available
medicines and when there is significant unmet medical need.
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 10% to 15% of patients in the US and Europe, and
30% to 40% of patients in Asia have epidermal growth factor receptor mutation-positive (EGFRm) NSCLC. 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 targets this secondary mutation that leads to disease progression. There is also a
need for agents with improved central nervous system efficacy since approximately 25% of patients with EGFRm NSCLC have brain
metastases at first 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 50
countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced non-small cell lung
cancer. Eligibility for treatment with TAGRISSO is dependent on confirmation that the EGFR T790M mutation is present in the
tumor.
TAGRISSO is also being investigated in the adjuvant and metastatic 1st-line settings, including in patients with and without CNS
metastases, in leptomeningeal metastases and in combination with other treatments.
About FLAURA
FLAURA assessed the efficacy and safety of osimertinib 80mg orally 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 study, with 556 patients across 30 countries.
The primary endpoint of the trial was progression-free survival, and secondary endpoints included overall survival, objective
response rate, duration of response, disease control rate, safety and measures of health-related quality of life.
About AstraZeneca in Lung Cancer
AstraZeneca is using ground-breaking science to develop a wide range of medicines for patients with lung cancer. We are
pioneering precision medicines that target molecular mutations in tumor cells, as well as those that aim to boost the power of the
immune response against cancer. We are committed to transforming outcomes for patients with lung cancer, whose treatment options
are currently limited.
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.
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.
US-15411 Last Updated 10/17
AstraZeneca
Michele Meixell, +1 302-885-2677
or
Stephanie Wiswall, +1 302-885-2677
View source version on businesswire.com: http://www.businesswire.com/news/home/20171009005571/en/