Shanghai Junshi Biosciences Co., a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, announced that the National Medical Products Administration (NMPA) has accepted for review the supplemental new drug application (sNDA) for toripalimab (trade name: TUOYI^®, product code: JS001) combined with bevacizumab for the first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC).

Liver cancer is a common malignant tumor of the digestive system worldwide, and the predominant pathological type is HCC (accounting for about 90% of global cases). According to the 2022 GLOBOCAN Report, there were 866,000 new cases and 759,000 deaths from liver cancer globally that year. China is particularly affected by liver cancer, with new liver cancer cases reaching 368,000 (accounting for 42.4% of global cases) in 2022, ranking fourth in new cases among domestic malignant tumors, and the number of deaths reaching 317,000 (accounting for 41.7% of global cases), ranking second among domestic malignant tumors. Due to its insidious onset, about 70%-80% of liver cancer patients in China are already at the intermediate or advanced stage upon first diagnosis, with a median OS of approximately only 10 months and a 5-year survival rate of approximately 12%. In recent years, the continuous emergence of combination therapies based on immunotherapy drugs has transformed the treatment landscape of advanced liver cancer, and achieving a radical cure after downstaging is gradually becoming a possibility.

The sNDA is based on the HEPATORCH study (NCT04723004), a multicenter, randomized, open-label, active-controlled phase III clinical study aiming to evaluate the efficacy and safety of toripalimab in combination with bevacizumab for the first-line treatment of unresectable or metastatic HCC compared to the standard treatment with sorafenib. Conducted across 57 centers nationwide in China, HEPATORCH was led by Principal Investigator Professor Jia FAN, President of Zhongshan Hospital affiliated to Fudan University and academician of the Chinese Academy of Sciences.

In June 2024, the primary endpoints of progression-free survival (PFS, based on independent radiological review) and overall survival (OS) of the HEPATORCH study met the pre-defined efficacy boundary. The results of the study showed that toripalimab in combination with bevacizumab for the first-line treatment of patients with advanced HCC could significantly prolong the PFS and OS of the patients compared with sorafenib, while improving the secondary endpoints such as objective response rate and time to progression. The safety profile of toripalimab was consistent with the known risks, and no new safety signals were identified. Further details will be presented at a future international academic conference.

Principal investigator Professor Jia FAN, Academician of Chinese Academy of Sciences and President of Zhongshan Hospital, said, “Due to the hidden onset of HCC, most domestic patients have already missed the opportunity for radical surgery at the time of initial diagnosis. The HEPATORCH study results show that first-line treatment of advanced HCC with toripalimab combined with bevacizumab offers significant survival benefits. The study also reaffirms the efficacy of combining immunosuppressants with anti-angiogenesis targeting drugs for advanced HCC. We eagerly await the approval of this therapy that combines toripalimab with bevacizumab, which will provide new treatment options for advanced HCC patients in China!”

“I’m delighted to see the successful submission of the sNDA for toripalimab’s 11^th indication,” General Manager and CEO of Junshi Biosciences, Dr. Jianjun ZOU, said. “Since receiving marketing approval in 2018 as the first domestically developed anti-PD-1 monoclonal antibody, toripalimab has targeted the unmet needs of cancer patients in China and even internationally. As of now, it has been approved for 10 indications in 7 cancer types, many of which are exclusive indications. This sNDA is toripalimab’s first indication in liver cancer, and once again, toripalimab is demonstrating its ‘broad-spectrum’ when battling cancer. Going forward, we will actively communicate with regulatory authorities to speed up the approval of this indication, so that more advanced liver cancer patients can benefit from our innovative therapy.”

About Toripalimab

Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells.

More than forty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and Europe. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types, including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney, and skin.

In the Chinese mainland, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI^®). Currently, there are eight approved indications for toripalimab in the Chinese mainland:

1. unresectable or metastatic melanoma after failure of standard systemic therapy;
2. recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy;
3. locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
4. in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC;
5. in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (ESCC);
6. in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC);
7. in combination with chemotherapy as perioperative treatment and subsequently with monotherapy as adjuvant therapy for the treatment of adult patients with resectable stage IIIA-IIIB NSCLC;
8. in combination with axitinib for the first-line treatment of patients with medium to high risk unresectable or metastatic renal cell carcinoma (RCC);
9. in combination with etoposide plus platinum for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC);
10. in combination with paclitaxel for injection (albumin-bound) for the first-line treatment of recurrent or metastatic triple-negative breast cancer (TNBC).

The first six indications have been included in the National Reimbursement Drug List (NRDL) (2023 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for the treatment of melanoma. In April 2024, the Drug Office at the Department of Health in the Government of the Hong Kong Special Administration Region (DO) accepted the NDA for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy.

In the United States, the US FDA has approved the Biologics License Application for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy in October 2023. The FDA has granted toripalimab 2 Breakthrough Therapy designations for the treatment of NPC, 1 Fast Track designation for the treatment of mucosal melanoma, and 5 Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer (SCLC).

In Europe, marketing authorization applications (MAA) were accepted by the European Medicines Agency (EMA) and the MHRA for 1) toripalimab combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC and 2) toripalimab combined with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC, in December 2022 and February 2023.

In Australia, the new chemical entity (NCE) application was accepted by the Australia Therapeutic Goods Administration (TGA) in November 2023. The TGA has also granted toripalimab an Orphan Drug designation for the treatment of NPC.

In Singapore, the NDA application was accepted by the Singapore Health Sciences Authority (HSA) in January 2024. The HSA has also granted priority review designation for the NDA.