BMS Submits Fourth Indication of Opdivo (Nivolumab) for Marketing Approval in China

Original: Cai Cai

Recently, Bristol-Myers Squibb’s Opdivo has filed for approval of its fourth indication in China. As the first PD-1 monoclonal antibody marketed in China, Opdivo has currently received approval for two indications: second-line treatment of non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck.

(Source: CDE)

Two Indications Approved, Two Indications Submitted for Marketing Approval

Bristol-Myers Squibb’s (BMS) PD-1 monoclonal antibody, nivolumab (brand name: Opdivo; commonly referred to as “O drug”), was the first PD-1 inhibitor approved for marketing in China. It received approval from the National Medical Products Administration (NMPA) in June 2018 for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK), and whose disease has progressed after or who are intolerant to prior platinum-based chemotherapy. In September 2019, it gained approval for a second indication: the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) whose disease has progressed during or after platinum-based therapy and whose tumors express PD-L1 (defined as ≥1% and ≥2% of tumor cells expressing PD-L1).

As of now, Opdivo (O drug) has two approved indications in China. Additionally, two more indications have been submitted for marketing approval, although the specific indications have not been disclosed. Since Opdivo has multiple indications currently in Phase III clinical trials, these two pending indications could potentially include small cell lung cancer, gastric cancer, renal cell carcinoma, esophageal cancer, and hepatocellular carcinoma, among others.

Opdivo currently has multiple clinical trials in China at Phase II and III stages. The table below lists the major clinical trials currently being conducted with Opdivo in China.

(Source: Drug Clinical Trial Registration and Information Publicity Platform)

6 PD-1 Inhibitors and 1 PD-L1 Inhibitor Approved for Marketing in China

As of now, a total of six PD-1 inhibitors and one PD-L1 inhibitor have been approved for marketing in China, four of which are domestically produced PD-1 inhibitors. Among them, pembrolizumab (brand name: Keytruda, commonly referred to as “K drug”) has the largest number of approved indications, totaling four, three of which are for non-small cell lung cancer (NSCLC), thereby securing a strategic foothold in the domestic lung cancer market. Among the domestically produced PD-1 monoclonal antibodies, except for toripalimab (brand name: Tuoyi), whose approved indication is second-line treatment of melanoma, the first approved indications for the other three agents are all third-line treatment of classical Hodgkin lymphoma. In addition, the second indication for tislelizumab—second-line treatment of urothelial carcinoma—has been submitted for marketing approval, while camrelizumab has submitted marketing applications for three indications: hepatocellular carcinoma, esophageal squamous cell carcinoma, and combination chemotherapy for non-squamous NSCLC, making it the domestically produced PD-1 inhibitor with the highest number of indications under review for approval.

PD-1/L1 Monoclonal Antibodies Marketed and Submitted for Marketing Approval in China

(Data source: CDE; statistics as of January 6, 2020)

Domestic Sales of All PD-1 Monoclonal Antibodies Exceed 100 Million Yuan

In the first half of 2019, toripalimab achieved sales of approximately RMB 310 million (over four months of sales); sintilimab recorded sales of RMB 330 million (nearly four months of sales); and camrelizumab’s sales in the third quarter of 2019 were estimated at approximately RMB 500 million (over two months of sales).

(Source: Official websites of respective companies)

Furthermore, only sintilimab was included in the new Class B National Reimbursement Drug List in 2019.

(Sourced from public information)

According to Frost & Sullivan’s forecasts, global sales are projected to reach $78.9 billion by 2030. Consequently, sales of PD-1 monoclonal antibodies are expected to continue rising in the coming years.

Global Market Size of PD-1/L1 Monoclonal Antibodies Will Continue to Increase

(Source: Frost & Sullivan)