Junshi Biosciences Announces FDA Orphan Drug Designation for Toripalimab in Combination with Axitinib for the Treatment of Mucosal Melanoma

On March 27, 2020 (Beijing Time), Junshi Biosciences announced that toripalimab (brand name: Tuoyi; product code: JS001), an anti-PD-1 monoclonal antibody independently developed by the company, in combination with axitinib for the treatment of mucosal melanoma, had recently been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA).

“Orphan drugs” refer to medications used to treat rare diseases. The United States enacted the Orphan Drug Act in 1983 and issued its latest revised version in 2013, granting special preferential rights to therapeutic agents for rare diseases affecting fewer than 200,000 patients in the U.S. The orphan drug designation recently awarded by the U.S. FDA for the combination therapy involving toripalimab will help secure certain policy supports for its subsequent research and development, registration, and commercialization in the United States. These benefits include tax credits for clinical trial expenses, waiver of new drug application fees, and seven years of market exclusivity unaffected by patent status. This will reduce R&D investment to some extent and facilitate the advancement of clinical trials.

Toripalimab is the first drug to receive “Orphan Drug” designation in the field of mucosal melanoma since the enactment of the Orphan Drug Act.

Notably, the FDA pointed out in its approval document to Junshi Biosciences that the indication for which orphan drug designation was granted is "mucosal melanoma," a scope broader than the indication submitted by Junshi Biosciences, with "unresectable or metastatic mucosal melanoma" included within this range. This means that toripalimab is expected to play a role in a larger therapeutic area.

Mucosal melanoma is a rare subtype of melanoma in Caucasians, accounting for approximately 1.3% of all melanoma cases; however, it is the second most common subtype among Asian patients, representing 22%–25% of cases. In addition to being more aggressive and prone to visceral metastasis, mucosal melanoma currently lacks established treatment guidelines, with both conventional chemotherapy and monotherapy immunotherapy demonstrating suboptimal efficacy. Preclinical studies have shown that combination immunotherapy can synergistically inhibit tumor growth, pointing to new therapeutic directions for the management of mucosal melanoma.

Toripalimab, independently developed by Junshi Biosciences, is the first domestically produced PD-1 inhibitor approved for marketing in China. Its currently approved indication in China is for locally advanced or metastatic melanoma after failure of prior standard therapy. To further enhance the efficacy of anti-PD-1 monoclonal antibody therapy in mucosal melanoma, Professor Guo Jun’s team at Peking University Cancer Hospital pioneered the combination regimen of toripalimab and axitinib, bringing an unprecedented breakthrough to first-line treatment options.

In 2017, the Phase Ib clinical study of “JS001 in combination with axitinib as first-line treatment for advanced mucosal melanoma” made its debut at the World Congress on Melanoma (2017 WCM). Updated results were subsequently presented at the American Society of Clinical Oncology Annual Meeting (2018 ASCO) and the Chinese Society of Clinical Oncology Annual Meeting (2018 CSCO), attracting global attention. Based on the breakthrough findings of this study, the combination of an anti-PD-1 monoclonal antibody and axitinib for the treatment of mucosal melanoma received a Level II expert recommendation in the 2019 edition of the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Melanoma.

In August 2019, the study was published in the prestigious international journal Journal of Clinical Oncology (IF: 28.245). The results showed that toripalimab combined with axitinib achieved an objective response rate (ORR) of 48.3% and a disease control rate (DCR) of 86.2% in patients with previously untreated advanced mucosal melanoma who had not received prior chemotherapy. The median progression-free survival (mPFS) was 7.5 months, while the median overall survival (mOS) was immature.

Dr. Yao Sheng, Vice President of Junshi Biosciences, stated, “The FDA’s granting of Orphan Drug Designation to us is a full recognition of our R&D exploration efforts. In the field of oncology, Junshi Biosciences places great emphasis on research into tumors that are sensitive to immunotherapy and those that are prevalent specifically in China. Upon identifying room for improvement in the efficacy of toripalimab for treating mucosal melanoma, which has a high incidence among the Chinese population, we decided to continue our exploration with the aim of finding more effective treatments for patients in China and around the world. Moving forward, Junshi Biosciences will continue to invest heavily in major disease areas such as cancer, contributing to the advancement of global human health.”

To date, Junshi Biosciences has conducted more than 30 clinical trials of toripalimab as monotherapy and in combination therapies worldwide, including 14 pivotal registration trials and one Phase Ib trial currently underway in the United States for multiple solid tumors, such as nasopharyngeal carcinoma, urothelial carcinoma, lung cancer, gastric cancer, esophageal cancer, liver cancer, and breast cancer.

Tuoyi (toripalimab injection), as the first domestically developed anti-PD-1 monoclonal antibody approved for marketing in China, has received support from the National Major Science and Technology Project. The first indication approved for this product is the treatment of unresectable or metastatic melanoma in patients who have failed prior systemic therapy, and it is recommended by the 2019 Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Melanoma. Clinical trial results demonstrated an objective response rate of 17.3%, a disease control rate of 57.5%, and a one-year survival rate of 69.3%. The approval of this product holds positive significance for expanding clinical treatment options for cancer patients in China.

Tuoyi initiated clinical development in early 2016 and has since conducted more than 30 clinical trials across multiple countries, including China and the United States, covering 14 tumor types. The drug is being actively investigated for efficacy in indications such as nasopharyngeal carcinoma, urothelial carcinoma, lung cancer, gastric cancer, esophageal cancer, liver cancer, and breast cancer. Collaborations with leading innovative pharmaceutical companies domestically and internationally on combination therapies are also underway, with the aim of providing more Chinese patients with access to state-of-the-art cancer immunotherapy.

Junshi Biosciences (NEEQ: 833330, HKEX: 01877) was founded in December 2012 by a team of graduates from renowned universities in China and the United States, with extensive experience in cross-border technology transfer and industrialization.

Junshi Biosciences focuses primarily on the development of therapeutic antibodies, specializing in the research, development, and industrialization of innovative monoclonal antibody drugs and other therapeutic protein drugs. The company boasts a robust pipeline of investigational products, including 18 innovative drugs and two biosimilars, covering four major therapeutic areas: malignant tumors, autoimmune diseases, chronic metabolic diseases, and neurological disorders. Junshi Biosciences is the first Chinese company to receive National Medical Products Administration (NMPA) marketing approval for an anti-PD-1 monoclonal antibody. It is also the first domestic company to obtain NMPA approval for Investigational New Drug (IND) applications for anti-PCSK9 and anti-BLyS monoclonal antibodies. Furthermore, it has secured IND approvals from both China’s NMPA and the U.S. FDA for the world’s first anti-BTLA blocking antibody for cancer treatment. Currently, Junshi Biosciences employs over 1,000 people worldwide, with operations in San Francisco and Maryland in the United States, and Shanghai, Suzhou, Beijing, and Guangzhou in China.