Qilu Pharmaceutical Submits NDA for First Domestic Generic Pazopanib Tablets for Advanced Renal Cell Carcinoma

On July 11, according to the New Drug R&D Monitoring Database (CPM), Qilu Pharmaceutical’s first generic drug for renal cell carcinoma, “Pazopanib Tablets,” had its marketing application accepted by the CDE.

Pazopanib (Votrient), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor developed by GSK, was transferred to Novartis as part of an asset swap transaction between GSK and Novartis in 2014. It is indicated for patients with advanced renal cell carcinoma and advanced soft tissue sarcoma.

Renal cell carcinoma is a common malignant tumor worldwide, with its incidence and mortality accounting for approximately 2%-3% of all systemic tumors. Among urological malignancies, its incidence ranks second only to bladder cancer and shows a逐年 increasing trend. In China, with the aging population and changes in lifestyle, the incidence of renal cancer continues to rise, with the growth rate ranking first globally.

Pazopanib has a mechanism of action similar to that of sorafenib, sunitinib, and axitinib. It was approved for marketing by the U.S. Food and Drug Administration (FDA) on October 20, 2009, and by the European Medicines Agency (EMA) on June 15, 2010. The incidence of serious adverse reactions is very low. Guidelines from the National Comprehensive Cancer Network (NCCN), European Association of Urology (EAU), European Society for Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO) all recommend pazopanib as a standard first-line treatment regimen for advanced renal cell carcinoma, based on Category 1 evidence. To date, it has been approved in more than 100 countries and regions worldwide for the treatment of advanced renal cell carcinoma.

In terms of clinical research, pazopanib has primarily conducted three large-scale clinical trials and is the first targeted therapy among all first-line targeted drugs for advanced renal cell carcinoma to have undergone a head-to-head comparative clinical study.

VEG105192, Phase III

VEG105192 was the first Phase III study comparing pazopanib with placebo, in which 435 patients with advanced renal cell carcinoma were randomized in a 2:1 ratio to receive either pazopanib or placebo. The results showed that the progression-free survival (PFS) was 9.2 months versus 4.2 months, and the objective response rate (ORR) was 30% versus 3% for the pazopanib group compared to the placebo group. In the subgroup of patients with treatment-naïve advanced renal cell carcinoma, the PFS reached 11 months versus 2.8 months. Pazopanib significantly improved PFS and was well tolerated.

COMPARZ, Head-to-Head

The COMPARZ study is a large-scale, international, multicenter, Phase III head-to-head clinical trial comparing pazopanib with sunitinib. A total of 1,110 subjects were enrolled, making it the only clinical trial to date that compares the efficacy of tyrosine kinase inhibitor (TKI) drugs as first-line treatment for advanced renal cell carcinoma.

Studies have shown that pazopanib not only demonstrates efficacy comparable to sunitinib in terms of progression-free survival (PFS) and overall survival (OS) in patients with advanced renal cell carcinoma (median PFS: 8.4 months vs. 9.5 months; OS: 28.3 months vs. 29.1 months; ORR: 31% vs. 25%), but also mitigates the severe adverse reactions associated with previous targeted therapies, thereby improving patients' quality of life.

Furthermore, it must be pointed out that in the COMPARZ China study (which included 207 patients from mainland China), pazopanib demonstrated a tumor response rate of 35% in the Chinese population, significantly higher than the 20% observed with sunitinib.

PISCES, Clinical Preference Study

The PISCES study primarily evaluated the treatment preferences of patients and physicians for pazopanib versus sunitinib. The results indicated that the majority of both patients and physicians preferred pazopanib.

Patients preferred pazopanib due to its milder adverse reactions, better quality of life, and greater acceptability. Physicians favored pazopanib because its progression-free survival (PFS) and overall survival (OS) were non-inferior to those of sunitinib, while its adverse reactions were relatively mild and easier to manage. This study differs from traditional clinical trials that focus primarily on survival outcomes and adverse events, providing stronger evidence that pazopanib is superior to sunitinib in terms of quality of life.

Pazopanib, recommended as a first-line treatment for advanced renal cell carcinoma in both domestic and international guidelines, has demonstrated favorable efficacy and safety profiles in a series of studies including VEG105192, COMPARZ, and PISCES. In clinical practice, it significantly reduces tumor burden while enabling patients to maintain a good quality of life, making it a preferred choice for both physicians and patients.

In terms of market performance, data from the Prescription Drug Database (PDB) indicates that in the global market, pazopanib’s growth rate reached 83% after the expansion of its indication to include soft tissue sarcoma in April 2012. However, its market growth rate has continued to decline in recent years, with sales amounting to USD 830 million in 2018 and a projected peak sales value of USD 1 billion.

Data Source: PDB Comprehensive Drug Database

Currently, the drugs approved in China for advanced renal cell carcinoma (RCC) mainly include sunitinib (Pfizer), sorafenib (Bayer), everolimus (Novartis), and axitinib (Pfizer). Among them, sunitinib and sorafenib are used for first-line treatment of advanced RCC; everolimus and axitinib are used for second-line treatment of patients with advanced RCC.

Pazopanib was approved by the National Medical Products Administration on February 21, 2017, for first-line treatment of patients with advanced renal cell carcinoma (RCC) and for the treatment of patients with advanced RCC who had previously received cytokine therapy. In October 2018, following price negotiations that resulted in a 65% reduction, it was included in the National Reimbursement Drug List alongside sunitinib and axitinib.

The Pharmaceutical Database (PDB) shows that in sample hospitals in China, the 200mg specification product is the main seller. Since pazopanib was included in the national medical insurance in Q4 2018, its sales volume has continued to increase, with both sales revenue and quantity rising.

Data Source: PDB Comprehensive Drug Database

However, although pazopanib has been included in the national medical insurance program, with its price per box reduced from RMB 13,800 to RMB 4,800, it still poses a considerable financial burden for most patients. The recent submission by Qilu Pharmaceutical for market approval of its generic version of pazopanib—the first such application in China—is undoubtedly another piece of good news for these patients.

According to the New Drug R&D Monitoring Database (CPM), the compound patent for pazopanib in China, CN1549813 (A), is set to expire on December 19, 2021, with no crystal form patents existing. At this juncture, Qilu Pharmaceutical’s submission of its first generic application appears to have been strategically timed.

In addition, besides Qilu Pharmaceutical, as of now, there are also multiple companies such as Yangtze River Pharmaceutical Group, Chia Tai Tianqing Pharmaceutical Group, and Hansoh Pharmaceutical engaged in the generic production of pazopanib formulations.

Data Source: Yao Fenxiang Plus