ghp December 2015 | 31 translation & commercialisation AstraZeneca today announced that the US Food and Drug Administration (FDA) has approved TAGRISSO™ (AZD9291) 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-ap- proved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy. AZD9291 is the only approved medicine indicated for patients with metastatic EGFR T790M mutation-pos- itive non-small cell lung cancer. This indication is approved under the FDA’s accelerated approval process based on tumour response rate and duration of response (DoR). AZD9291 is an EGFR-TKI, a targeted cancer therapy, designed to inhibit both the activating, sensitising mutations (EGFRm), and T790M, a genetic mutation responsible for EGFR-TKI treatment resistance. Nearly two-thirds of NSCLC patients who are EGFR muta- tion-positive and experience disease progression after being treated with an EGFR-TKI develop the T790M resistance mutation, for which there have been limited treatment options. Pasi A Jänne M.D., PhD, Director, Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, Scientific Director, Belfer Center for Applied Cancer Science and Professor of Medicine, Harvard Medical School said: “In the AURA clinical studies, AZD9291 has demonstrated compelling early efficacy and tolerability in patients with EGFRm T790M metastatic non-small cell lung cancer. This treatment has the potential to become the standard of care for patients living with EGFRm T790M non-small cell lung cancer. The accelerated approval of AZD9291 highlights its clinical promise for a targeted group of patients and gives healthcare providers an important new option.” Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “The FDA approval of TAGRISSO marks an im- portant milestone for lung cancer patients who urgent- ly need new treatment options. We have built on our heritage in this area and acted on the breakthrough clinical evidence to ensure this next-generation med- icine reaches patients in record time. As we advance our comprehensive lung cancer portfolio, we have the opportunity to treat greater numbers of patients across all stages of this disease through precision medicines, immunotherapies and novel combinations.” AstraZeneca has collaborated with Roche to develop the cobas® EGFR Mutation Test v2 as the companion diagnostics for AZD9291. The cobas® EGFR Muta- tion Test v2 is intended to identify a range of EGFR mutations in patients with non-small cell lung cancer, including T790M. AZD9291 was granted Fast Track, Breakthrough Therapy, Priority Review and Accelerated Approval status by the FDA. In Europe and Japan, AZD9291 was granted Accelerated Assessment and Priority Review status respectively. Interactions with regulatory authorities in the rest of the world are ongoing. The FDA approval of AZD9291 is based on data from the two AURA Phase II studies (AURA extension and AURA2) which demonstrated efficacy in 411 EGFRm T790M NSCLC patients that had progressed on or after an EGFR TKI. In those trials, overall objective response rate ((ORR) a measurement of tumour shrinkage) was 59% (95% CI: 54% to 64%). In a sup- portive Phase I study in 63 patients, ORR was 51% and median duration of response was 12.4 months. The AZD9291 tolerability profile showed that no individual severe grade 3+ adverse events occurred at ≥ 3.5%.The most common adverse events were gen- erally 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). There are no contraindications for AZD9291. Warnings and precautions include interstitial lung disease, QT interval prolongation, cardiomyopathy and embryofetal toxicity. AZD9291 Development Programme AZD9291 is being studied in the confirmatory trial, AURA3, an open label, randomised Phase III study designed to assess the efficacy and safety of AZD9291 versus platinum-based doublet chemotherapy in patients with EGFR T790M positive, locally advanced, or metastatic NSCLC who have progressed following prior therapy with an EGFR-TKI. AZD9291 is also being investigated in the adjuvant setting and in the metastatic first-line setting, including in patients with brain metastases, as well as in combination with other compounds. One of fastest development programmes – from start of clinical trials to approval in just over two and a half years to meet unmet patient need. Ongoing Accelerated Assessment in the EU and Priority Review in Japan.