EC conditionally approves AstraZeneca’s TAGRISSO under its new policy

Approval for the drug in Europe that is yet to be approved in India, is based on studies showing objective response rate of 66% and median progression-free survival of 9.7 months

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AstraZeneca has announced that the European Commission (EC) has granted conditional marketing authorisation for TAGRISSO™ (AZD9291, osimertinib) 80mg once-daily tablets for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC). TAGRISSO™ is the first new medicine to be approved under the European Commission’s expedited process.

Osimertinib is indicated for patients with T790M mutation-positive NSCLC, irrespective of previous treatment with an EGFR tyrosine kinase inhibitor (TKI). Eligibility for treatment with osimertinib will be dependent on mutation status, to be determined through a validated diagnostic test based on a tumour tissue sample or plasma. Availability of a blood-based test for circulating tumour DNA (ctDNA) means that physicians and patients have multiple options to test for a T790M mutation.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “Osimertinib defines a new generation of targeted EGFR-TKI treatments, and the European Commission’s expedited approval reflects the importance of this innovative medicine for addressing the needs of patients with lung cancer who have the T790M mutation. We are now building on our understanding of the clinical activity of osimertinib to explore its full potential in patients with EGFRm lung cancer in multiple treatment settings.”

Dr Matthew Peters, Chair of the Global Lung Cancer Coalition, added: “It is an exciting time in the care of patients with lung cancer. The ability to precisely characterise patients who have different types of lung cancer based on genetic mutations, and predict their response to targeted treatments, offers a more accurate and efficient approach to lung cancer care. Patients with common sensitising EGFR mutations and the separate T790M have disappointing responses to standard treatments. Testing for the T790M status of lung cancer patients, using either a tumour sample or a simple blood test, and directing patients towards a medication such as osimertinib that is specifically designed for their pattern of mutations, offers greater prospects for durable treatment outcomes.”

Mutations in the EGFR receptor can lead to uncontrolled cell growth and tumour formation. Osimertinib targets both the EGFR mutation that triggers cancer development and T790M, a mutation that makes tumours resistant to existing treatment with EGFR-TKIs. Nearly two out of three patients with NSCLC whose disease progresses after treatment with an EGFR inhibitor develop the T790M mutation, for which treatment options are limited. A small number of patients (approximately 3-5%) have the T790M mutation at NSCLC diagnosis.

The EU approval for osimertinib is based on data from two Phase II studies (AURA extension and AURA2) and the AURA Phase I expansion study, which demonstrated efficacy in 474 patients with EGFRm T790M NSCLC who had progressed on or after an EGFR-TKI. In the combined Phase II studies, the objective response rate (ORR, a measurement of tumour shrinkage) was 66%, and in the Phase I study it was 62%. Progression-free survival (PFS) was 9.7 months in the combined Phase II studies and 11 months in the Phase I trial. Median duration of response (DOR) in the Phase I study was 9.7 months, and in the combined Phase II studies, median DOR was not reached.

The most common adverse events based on data from the two AURA Phase II studies were generally mild to moderate and included diarrhoea (42% all grades; 1.0% Grade 3/4), rash (41% all grades; 0.5% Grade 3/4), dry skin (31% all grades; 0% Grade 3/4) and nail toxicity (25% all grades; 0% Grade 3/4). Warnings and precautions include interstitial lung disease and QT interval prolongation.

The EU marketing authorisation was received through the Accelerated Assessment procedure of the European Medicines Agency (EMA). This approval follows US Accelerated Approval granted in November 2015 and availability in the UK under the Early Access to Medicines Scheme in December 2015. In Japan, osimertinib was granted Priority Review by the Pharmaceuticals and Medical Devices Agency (PMDA). Interactions with regulatory authorities in the rest of the world are ongoing.

Tagrisso is yet to be approved in India.