Pharnex Cloud Data (www.pharnexcloud.com)Monitoring Shows: On February 16, 2024, AstraZeneca's (AZ) Tagrisso (Osimertinib, AZD9291) in combination with chemotherapy was approved in the United States for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).

The approval by the U.S. Food and Drug Administration (FDA) under Priority Review was based on the results of the FLAURA2 Phase III trial published in The New England Journal of Medicine. Compared with the global standard first-line treatment of osimertinib monotherapy, the combination of osimertinib and chemotherapy reduced the risk of disease progression or death by 38% (Hazard Ratio [HR]: 0.62; 95% Confidence Interval [CI] 0.49-0.79; p<0.0001). Investigator-assessed results showed that the median progression-free survival (PFS) was extended to 25.5 months with the combination of osimertinib and chemotherapy, an increase of 8.8 months compared to 16.7 months with osimertinib monotherapy.

PFS assessed by investigators and BICR; FLAURA2 study and data from the Chinese cohort

This is consistent with the PFS results assessed by the Blinded Independent Central Review (BICR): the combination of osimertinib and chemotherapy extended the median Progression-Free Survival (PFS) to 29.4 months, compared to osimertinib monotherapy (median PFS of 19.9 months), prolonging the median PFS by 9.5 months (HR: 0.62; 95% CI 0.48-0.80; p=0.0002).

The data from the Chinese cohort of the FLAURA2 study showed that, compared with osimertinib monotherapy, the median PFS assessed by INV was 27.4 months versus 22.3 months (HR=0.56, 95% CI: 0.34-0.92); the median PFS assessed by BICR was 33.2 months versus 22.0 months (HR=0.58, 95% CI: 0.34-1.01) (Figure 1); both INV PFS and BICR PFS results were highly consistent, with HRs of 0.56 and 0.58, respectively; the mPFS of osimertinib monotherapy reached 22 months, and compared with monotherapy, the combination of osimertinib and chemotherapy demonstrated significantly greater benefit.

In the United States, more than 200,000 people are diagnosed with lung cancer each year, of which 80%-85% are non-small cell lung cancer, the most common type of lung cancer. Approximately 70% of non-small cell lung cancer cases are already at an advanced stage at the time of diagnosis. Additionally, about 15% of non-small cell lung cancer patients in the U.S. have EGFR mutations.

In December 2023, based on the FLAURA2 study, osimertinib combined with chemotherapy was included as a "Category 1 recommendation - Other Recommended Regimens" in the NCCN Clinical Practice Guidelines® (NCCN Guidelines®) for the treatment of patients with non-small cell lung cancer harboring EGFR Exon 19 Del/Exon 21 L858R mutations.

The US registration application document is currently under review in the Orbis project, which aims to provide a collaborative framework for regulatory authorities to conduct joint submissions and approvals of oncology drugs. As part of the project, osimertinib in combination with chemotherapy is also under review by regulatory agencies in Australia, Canada, and Switzerland. Meanwhile, based on the results of the FLAURA2 study, the registration application is also undergoing review in several other countries.

Osimertinib has been approved as a monotherapy in more than 100 countries, including the United States, the European Union, China, and Japan, for the first-line treatment of patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer, the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer, and adjuvant treatment for patients with early-stage EGFR-mutated non-small cell lung cancer.

In 2023, this product became a performanceOne of the strongest small-molecule tumor drugs: $5.799 billion`, second only to`BMS Lenalidomide's $6.097 Billion(top1)。

On April 25, 2024, AstraZeneca disclosed its Q1 2024 performance, with revenue of $12.679 billion, representing a 19% increase year-over-year on a CER basis.Among them,2024 Q1 OsimertinibIncreased by 15%, with sales revenue of $1.595 billionIn addition, the global total sales of Enhertu (HER2 ADC) in the first quarter were 879 million US dollars.

It is worth noting that,Other domestically produced new drugs that approached or exceeded 2 billion RMB in performance in 2023 include: Hansoh Pharma/Hausen Pharmaceutical's Almonertinib, Allist's Furmonertinib, BeiGene's Zanubrutinib, CT Tianqing's Anlotinib, Innovent Biologics' PD-1, Hengrui Medicine's PD-1, CSPC Pharmaceutical Group's Butylphthalide, Johnson & Johnson/ Legend Biotech's BCMA CAR-T, BeiGene's PD-1, 3SBio's TPO, etc.

Reference:

NMPA/CDE；

Pharnex Cloud Data www.pharnexcloud.com;

FDA/EMA/PMDA；

Relevant companies publicly disclosed;

https://www.astrazeneca.com;

https://www.astrazeneca.com/investor-relations/q1-2024-results-event.html;

https://www.businesswire.com/news/home/20240216171764/en/TAGRISSO%C2%AE-osimertinib-with-the-addition-of-chemotherapy-approved-in-the-US-for-patients-with-EGFR-mutated-advanced-lung-cancer；

NCCN, National Comprehensive Cancer Network® (NCCN®). Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer Version 1.2024.© National Comprehensive Cancer Network, Inc. [2024]. All rights reserved. Accessed [February 14, 2024]. To view the most recent and complete version of the guideline, go online to NCCN.org；

Planchard D, Planchard D, Cheng Y, et al. Osimertinib With/Without Platinum-Based Chemotherapy as First-line Treatment in Patients with EGFRm Advanced NSCLC (FLAURA2). 2023 WCLC. Abstract PL03.13; etc.