Aosaikang Pharma Submits China's First Generic Ceritinib Capsule NDA Following Crizotinib

On February 23, the Center for Drug Evaluation (CDE) accepted the registration application for ceritinib capsules, a Class 4 generic drug from Jiangsu Aosaikang Pharmaceutical Co., Ltd. This marks Jiangsu Aosaikang Pharmaceutical Co., Ltd. as the first company in China to submit a marketing application for a generic version of ceritinib.

Ceritinib (Zykadia), the original research drug developed by Novartis, is an anaplastic lymphoma kinase (ALK) inhibitor. Studies have shown that ceritinib is approximately 20 times more potent than crizotinib in inhibiting ALK. It is effective not only in patients who have developed resistance to crizotinib but also in those with brain metastases who are resistant to crizotinib.

In April 2014, Zykadia received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who had experienced disease progression after crizotinib therapy or who were intolerant to crizotinib. In May 2017, the drug was further approved by the FDA as a first-line treatment for ALK-positive metastatic NSCLC, becoming the second targeted therapy approved for first-line use in ALK-positive NSCLC, following Pfizer’s crizotinib.

In China, ceritinib was first approved by the NMPA in May 2018 for patients with ALK-positive non-small cell lung cancer (NSCLC) who had experienced poor response or developed resistance after crizotinib treatment, under the brand name Zykadia. Last May, the drug received additional approval in China for first-line treatment of patients with ALK-positive NSCLC.

It is reported that at the 2020 ESMO Congress, data from the Asian subgroup of the ASCEND-8 study on ceritinib as first-line treatment for patients with ALK-positive NSCLC showed that: as of March 6, 2020, with a median follow-up time of 37.65 months, the median PFS had not yet been reached. Among them, the 450 mg ceritinib group taken with meals had a 3-year PFS rate of 58.9%, an OS rate of 93.1%, a DCR of 96.6%, an ORR of 82.8%, and a 3-year DOR rate of 68.2%.

Furthermore, the results of the ASCEND-7 prospective clinical study evaluating ceritinib in patients with symptomatic/progressive brain metastases and leptomeningeal metastases demonstrated that: In all ALK-positive patients with symptomatic/progressive brain metastases, regardless of prior treatment with crizotinib or cranial radiotherapy, the disease control rate (DCR) exceeded 70%. Among all patients with measurable brain metastases at baseline, the DCR reached over 75%, confirming robust efficacy. In patients with leptomeningeal metastases, despite poor baseline characteristics, the objective response rate (ORR) was 20%, with a median progression-free survival (PFS) of 5.2 months and an overall survival (OS) of 7.2 months.

As the only ALK inhibitor with prospective evidence-based data for symptomatic/advanced brain metastases and leptomeningeal metastases, ceritinib has been recommended by the Pan-Asian ESMO Guidelines for Advanced NSCLC as a first-line treatment regimen for ALK-positive brain and leptomeningeal metastases.

Furthermore, ceritinib was included in the National Reimbursement Drug List (NRDL) in China through price negotiations in 2018, with a reimbursement standard of RMB 198 per 150 mg capsule. Last year, its indication for first-line treatment of ALK-positive non-small cell lung cancer (NSCLC) was also covered by the national medical insurance. It is anticipated that, with the expansion of reimbursement coverage and price reductions, ceritinib will benefit a broader patient population.

Jiangsu Aosaikang Pharmaceutical Co., Ltd. has taken the lead in submitting a Class 4 generic drug marketing application for ceritinib capsules, positioning itself to potentially secure the first generic approval for this medication. Furthermore, according to the Insight database, other pharmaceutical companies, including CSPC Pharmaceutical Group, Simcere Pharmaceutical Group, and Chia Tai Tianqing Pharmaceutical Group, are also entering the ceritinib generic market.

Regarding ALK inhibitors, four agents have currently been approved in China: the first-generation crizotinib (Pfizer), the third-generation alectinib (Roche), and the second-generation ceritinib (Novartis) and ensartinib (Betta Pharmaceuticals). Among these, ensartinib is the only domestically developed, original ALK inhibitor independently researched and developed in China. Clinical study data have demonstrated that, compared with the crizotinib treatment group (Pfizer), the ensartinib treatment group achieved a significantly prolonged median progression-free survival (PFS) and a significantly reduced risk of disease progression or death. The domestic market for the other three ALK inhibitors remains entirely monopolized by their originator products. However, in January this year, Wanbang Pharmaceutical submitted a marketing application for a Class 4 generic version of crizotinib capsules. Additionally, Takeda Pharmaceutical has also submitted an import application in China for the second-generation ALK inhibitor brigatinib tablets.