First Domestic Teriflunomide Generic by Nanjing Haina Pharma and SystImmune BioPharma Nears Approval in China

Recently, the marketing application (related acceptance number: CYHS2000166) for the Category 4 generic drug "Teriflunomide Tablets" by NANJING HEALTHNICE PHARMACEUTICAL CO., LTD. / Shengshi Taike Biopharmaceutical Technology (Suzhou) Co., Ltd. has changed to "Under Review" at the NMPA. It is expected to be officially approved soon, becoming the first China-produced Teriflunomide to be approved in China.

Teriflunomide is an immunomodulator that blocks the de novo synthesis of pyrimidines by inhibiting dihydroorotate dehydrogenase. The original Teriflunomide (brand name: Aubagio) was developed by Sanofi and was first approved by the FDA in September 2012 for the treatment of adult relapsing multiple sclerosis (RMS). It was then approved by the EMA in September 2013 for the treatment of adult relapsing-remitting multiple sclerosis (RRMS). In June 2021, Aubagio was further approved by the EMA as a first-line treatment for RRMS pediatric patients aged 10-17, becoming the first oral MS therapy approved by the EU for the first-line treatment of MS in children and adolescents.

According to the company's financial report, the sales of Aubagio have continued to grow after its launch, reaching 2.045 billion euros in 2020. The approval of pediatric indications is expected to become a new growth driver for Aubagio's sales.

In China, the original teriflunomide (brand name: Aubagio) was first approved by the NMPA in July 2018 for the treatment of relapsing MS, becoming the first oral disease-modifying therapy (DMT) drug approved in the country. In August 2020, Aubagio was also approved by the NMPA for the treatment of clinically isolated syndrome (CIS). Teriflunomide entered the national medical insurance system in 2019 and successfully renewed its listing in 2021; however, unfortunately, the insurance coverage is still limited to multiple sclerosis patients who have not responded to conventional treatments.

According to the Insight database, currently, eight companies in China are tapping into the teriflunomide generic drug market. Among them, NANJING HEALTHNICE PHARMACEUTICAL CO.,LTD/CGeneTech and Chenxin Pharmaceutical have successively submitted applications for the marketing approval of Class 4 generic drugs. Rayne Pharmaceutical is in the BE trial stage. This time, the Class 4 generic drug marketing application for teriflunomide by NANJING HEALTHNICE PHARMACEUTICAL CO.,LTD/CGeneTech has entered the administrative approval stage and is expected to become the first domestically produced teriflunomide approved in China.

Multiple Sclerosis (MS) is a serious, lifelong, progressive, and disabling demyelinating disease of the central nervous system. Based on the disease course, MS can be divided into four types: Relapsing-Remitting MS (RRMS, accounting for about 85%), Secondary Progressive MS (SPMS), Primary Progressive MS (PPMS, accounting for about 10%), and Progressive Relapsing MS (PRMS, accounting for about 5%), of which 80% of RRMS can develop into SPMS. According to statistics, there are about 20 million MS patients globally, and approximately 30,000 diagnosed MS patients in China.

Disease-modifying treatment (DMT) is the standard treatment for MS patients during remission. In recent years, NMPA has approved five DMT drugs, as detailed in the table below. Among them, fingolimod and siponimod are selective sphingosine-1-phosphate receptor (S1PR) modulators that work by binding to the S1P1 subtype receptor in lymphocytes, preventing them from entering the central nervous system of MS patients, thereby suppressing inflammation. The mechanism of action of dimethyl fumarate in treating MS is not yet fully understood but is believed to activate the nuclear factor-related factor 2 (NRF2) pathway, reducing oxidative stress-induced cellular damage. Extended-release dalfampridine is the first drug proven to improve walking ability in adult MS patients and has demonstrated its clinical efficacy in this population. Ocrelizumab, a CD20-targeted monoclonal antibody, was later developed by Novartis as a B-cell depleting agent for MS treatment. Currently, except for dimethyl fumarate and ocrelizumab, the other four drugs have been included in the 2021 National Medical Insurance Catalog in China.