Qilu Pharmaceutical's Afatinib Dimaleate Tablets Set to Become China's Second Approved Generic

Author | Cai Cai

Recently, the marketing application for Qilu Pharmaceutical’s “Afatinib Maleate Tablets” (acceptance numbers: CYHS1800519, 521, 522) has been updated to “under review,” with approval expected in the near future. Qilu will become the second pharmaceutical company to receive marketing approval for this product.

As the application is submitted under the new Class 4 generic drug category, approval will be deemed equivalent to passing the consistency evaluation.

(Source: NMPA)

Afatinib Maleate Tablets (Afatinib, brand name: Gilotrif®/Gilotri) are a selective, irreversible tyrosine kinase inhibitor developed by Boehringer Ingelheim. It binds to ErbB family receptors (EGFR, HER2, ErbB3, and ErbB4), thereby inhibiting tyrosine kinase activity and suppressing tumor growth. It belongs to the second generation of EGFR-TKIs.

Afatinib, developed by Boehringer Ingelheim, was first approved by the U.S. FDA in July 2013. In March 2017, it received approval from China’s National Medical Products Administration (NMPA) for two indications: first-line treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, and second-line treatment for patients with squamous cell lung cancer. It is available in strengths of 30 mg, 40 mg, and 50 mg. Currently, the 30 mg and 40 mg formulations are included in Category B of China’s National Reimbursement Drug List. Afatinib is the first second-generation EGFR-TKI to be marketed globally and in China.

(Source: Yaozhi Data)

Compared with the first-generation gefitinib, afatinib primarily distinguishes itself by its ability to comprehensively and simultaneously inhibit all members of the ErbB family, binding irreversibly to the receptors, thereby effectively and durably blocking downstream signal transduction.

Afatinib Demonstrates Superior Efficacy Compared to Chemotherapy

Clinical results from two independently conducted Phase III trials in patients with EGFR mutation-positive metastatic non-small cell lung cancer (NSCLC)—the global LUX-Lung 3 study and the Asian LUX-Lung 6 study—demonstrated that first-line afatinib significantly improved survival benefits and reduced the risk of death compared with standard chemotherapy in patients harboring the Del19 mutation. The median overall survival (OS) was 33.3 months versus 21.1 months in the LUX-Lung 3 study, and 31.4 months versus 18.4 months in the LUX-Lung 6 study. The control chemotherapy regimen in the LUX-Lung 3 study was pemetrexed/cisplatin, whereas that in the LUX-Lung 6 study was gemcitabine/cisplatin.

Afatinib Demonstrates Efficacy Advantages Over First-Generation TKIs

LUX-Lung7 is the first prospective, randomized, open-label trial to evaluate afatinib versus the first-generation EGFR-TKI gefitinib in patients with EGFR mutation-positive NSCLC. Compared with gefitinib, afatinib significantly improved efficacy, with consistent results observed across all trial subgroups. First-line treatment with afatinib reduced the risk of lung cancer progression by 27%, and the improvement in progression-free survival (PFS) with afatinib became more pronounced over time compared with gefitinib (HR=0.73, P=0.0165; at 18 months, 27% vs. 15%, P=0.0176; at 24 months, 18% vs. 8%, P=0.0184).

7 Applicants; Hansoh Wins First Generic Approval

Data from Menet shows that in 2019, the sales revenue of Afatinib Maleate Tablets at the terminal level of China's public medical institutions—including urban public hospitals, county-level public hospitals, urban community health centers, and township health centers—reached RMB 260 million, representing a year-on-year increase of 2,148.36%.

To date, a total of seven companies have submitted marketing applications for generic afatinib maleate tablets under Class 4. In June 2020, Hansoh Pharmaceutical secured approval for the first generic version.

(Source: CDE)

Lung cancer is one of the most common malignant tumors in China, with approximately 600,000 new cases diagnosed annually, and it ranks as the leading cause of cancer-related deaths[4]. With advances in lung cancer treatment research, it has been found that patients with specific gene mutations benefit more from targeted therapy than from chemotherapy.

Common genetic mutation types in lung cancer include EGFR, ALK, and KRAS, with varying distributions across different ethnic groups. Among lung cancer patients in Europe and the United States, the EGFR mutation rate is approximately 10–15%, whereas it reaches as high as 50% in Chinese patients with non-small cell lung cancer (NSCLC). Targeted therapies against EGFR can be said to be tailor-made for Chinese lung cancer patients.

Currently, there are 7 EGFR-TKIs marketed globally, all of which are available in China.

Globally Marketed EGFR-TKIs

(Data source: Insight database)

References:

1、Park K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol (link is external). 2016;17(5):577-89

2、 Yang J, Wu Y-L, Schuler M, et al. Afatinib versus cisplatin chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015;16(2):141-51