AstraZeneca, Daiichi Sankyo get USFDA accelerated nod for Enhertu for HER2 Mutant Non-small Cell Lung Cancer

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The accelerated approval by the FDA was based on the results from the DESTINY-Lung02 Phase II trial. An interim efficacy analysis in a pre-specified patient cohort showed Enhertu (5.4mg/kg) demonstrated a confirmed ORR of 57.7% (n=52; 95% confidence interval [CI] 43.2-71.3), as assessed by blinded independent central review (BICR), in patients with previously treated unresectable or metastatic non-squamous HER2-mutant (HER2m) NSCLC. Complete responses (CR) were seen in 1.9% of patients and partial responses (PR) in 55.8% of patients with a median DoR of 8.7 months (95% CI 7.1-NE). Results from the DESTINY-Lung02 trial will be presented at an upcoming medical meeting.

Bob T. Li, MD, PhD, MPH, Medical Oncologist and Physician-Scientist, Memorial Sloan Kettering Cancer Center, US, said: "The approval of trastuzumab deruxtecan in non-small cell lung cancer is an important milestone for patients and the oncology community. After two decades of research into the role of targeting HER2 in lung cancer, the approval of the first HER2-directed treatment option validates HER2 as an actionable target in lung cancer and marks an important step forward for treating this patient population with unmet medical needs."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "HER2-mutant non-small cell lung cancer is an aggressive form of disease which commonly affects young patients who have faced limited treatment options and a poor prognosis to date. Today's news provides these patients with the opportunity to benefit from a targeted therapy and highlights the importance of testing for predictive markers, including HER2 in lung cancer, at the time of diagnosis to ensure patients receive the most appropriate treatment for their specific disease."

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc, said: "We are excited that the FDA has granted accelerated approval for Enhertu for patients with HER2-mutant metastatic non-small cell lung cancer. Enhertu has now been approved in three different tumour types, underscoring its significant potential across several HER2-targetable tumours. We are continuing to evaluate the efficacy and safety of Enhertu versus standard chemotherapy in our DESTINY clinical trials in lung cancer."

The safety of Enhertu was evaluated in an analysis of 101 patients with unresectable or metastatic HER2m NSCLC who received at least one dose of Enhertu (5.4mg/kg) in the DESTINY-Lung02 trial. In the analysis, the safety profile of Enhertu was consistent with previous clinical trials with no new safety concerns identified.

Concurrently with this approval, the FDA also approved companion diagnostic tests to detect HER2 mutations in lung tumour tissue and plasma. This is the third tumour type approved by the FDA for Enhertu in three years, following approval in breast and gastric cancers. The approval follows the recently received Priority Review in the US as well as the Breakthrough Therapy Designation granted in 2020 by the FDA for this specific type of lung cancer based on the results of the DESTINY-Lung01 trial.

Following US approval, an amount of $125m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the HER2-mutant metastatic NSCLC indication. The milestone will be capitalised as an addition to the upfront payment made by AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalised milestones, and will be amortised through the profit and loss statement.

Sales of Enhertu in the US are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in the US as collaboration revenue in the Company's financial statements.

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