Novartis' Fingolimod Hydrochloride (Gilenya) Set for Imminent Launch in China, Bringing New Hope to Multiple Sclerosis Patients

Author: Cai Cai

Breaking News! Novartis’ Fingolimod Hydrochloride (brand name: Gilenya) is set to launch in the Chinese market. As the world’s first oral medication for the treatment of multiple sclerosis (MS), it achieved global sales of $3.341 billion in 2018, rightfully earning its status as a “blockbuster drug.”

According to the NMPA website, the status of the marketing application for fingolimod has been updated to "under review," with a high probability of launch this month.

(Source: NMPA Official Website)

Blockbuster in the MS Field

Overview

Fingolimod is a novel immunosuppressant developed by Novartis.

This drug was initially isolated from the fungus *Sinclairia cordyceps* and its close relative, *Cordyceps sinensis*, as a compound with potent immunosuppressive activity. It belongs to the class of sphingosine-1-phosphate receptor (S1PR1/S1PR3/S1PR4/S1PR5) modulators. Fingolimod is a prodrug and a substrate for sphingosine kinase 2 (SPHK2). In vivo, it is phosphorylated by SPHK2 to form the active phosphate ester, (S')-FTY720-P, which acts as a full agonist at S1P1, S1P3, S1P4, and S1P5 receptors. By activating the S1P1 receptor, (S')-FTY720-P induces receptor internalization, thereby exerting a functional antagonistic effect. This inhibits S1P1-mediated lymphocyte migration, promoting the retention of T lymphocytes within lymph nodes and triggering the "homing" of peripheral lymphocytes, ultimately resulting in immunosuppression.

Structural Formula of Fingolimod

Approved Indications

It has been approved in the United States, the European Union, and Japan, and a marketing application was submitted to the NMPA in April 2019.

(Data Source: Yaozhi Data)

Approved indications include multiple sclerosis (MS) and relapsing-remitting multiple sclerosis (RRMS).

(Compiled from public sources)

Adverse Reactions

On November 20, 2018, the FDA issued a warning stating that discontinuation of fingolimod treatment in patients with multiple sclerosis (MS) may lead to severe disease exacerbation, potentially resulting in permanent disability. Therefore, the FDA recommends that patients be informed of the risk of disability associated with the drug prior to initiation of therapy, and that they be closely monitored for adverse reactions following discontinuation.

Patent Layout

Currently, there are over 100 global patent applications for fingolimod. The originator company has secured protection for fingolimod through a series of patents. For instance, its parent patent, US-5604229, was granted a five-year extension in December 2010 and expired in February 2019. The combination product patent, US-08324283, has been granted in most major markets and is set to expire in 2026. In January 2016, a new use patent (US-09187405) was granted and will expire in 2027.

Global Sales

Since its market launch in 2010, fingolimod sales have continued to grow, reaching $3.341 billion globally in 2018; however, given the exposure to numerous adverse reactions, the future global sales growth rate of fingolimod may slow down.

(Source: Company Annual Report)

There are only two drugs for the treatment of MS in China.

Multiple Sclerosis (MS) is an autoimmune disease primarily characterized by inflammatory demyelination of proteins in the central nervous system. Currently, approximately 2.5 million people worldwide are affected by MS, with a higher prevalence among young adults aged 20 to 40 years. Female patients outnumber male patients by a ratio of two to one. The exact cause of the disease remains unknown, but it is generally believed to be associated with genetic, environmental, and autoimmune factors.

MS is classified into four subtypes, each with its own characteristics.

(Compiled from publicly available information)

There is currently no effective curative therapy for multiple sclerosis (MS); clinical management primarily relies on disease-modifying therapies (DMTs). Medications for MS are mainly categorized into three classes: immunomodulators, immunosuppressants, and anti-inflammatory agents.

According to the guidelines for the diagnosis and treatment of rare diseases and publicly available information from the international multiple sclerosis (MS) community, a total of 16 drugs for the treatment of MS have been approved for market entry to date. Interferon beta (IFNβ) and glatiramer acetate (brand name: Copaxone) are first-line therapies for relapsing-remitting MS, administered via subcutaneous or intramuscular injection. Natalizumab (brand name: Tysabri) and mitoxantrone (brand name: Novantrone) are primarily used as second-line treatments and require intravenous infusion under the supervision of qualified healthcare professionals.

As multiple sclerosis (MS) is a chronic disease requiring long-term medication, there is a strong patient demand for oral therapies. Currently, three oral MS drugs are available globally: fingolimod hydrochloride (brand name: Gilenya), teriflunomide (brand name: Aubagio), and dimethyl fumarate (brand name: Tecfidera).

(Source: FDA, NMPA)

According to the “Survival Report for Patients with Multiple Sclerosis (2018)” released by the Neurology Branch of the Chinese Medical Association, only two disease-modifying therapies for multiple sclerosis (MS) have been approved for marketing in China, namely interferon beta-1a and teriflunomide; consequently, the medical burden on patients is particularly heavy. For more information, please read the related article on this official WeChat account: “Limited Drug Options and Heavy Burden: An Analysis of the Current Treatment Landscape for Patients with Multiple Sclerosis in China.”

New Drugs Urgently Needed for Clinical Use That Have Been Marketed

MS was included in the First Batch of Rare Diseases Catalogue in May 2018, and fingolimod was listed among the 48 urgently needed new drugs already marketed overseas, as released by the CDE in August of the same year.

(Source: NMPA)

Novartis' Second-Generation MS Drug Siponimod

Due to the adverse reactions associated with fingolimod, Novartis developed siponimod (code: BAF312), a second-generation MS drug, and submitted its marketing application to the NMPA in February this year. Although the submission was made two months earlier than that of fingolimod, the approval date is likely to be later than that of fingolimod.

The Power of Generic Drugs Should Not Be Underestimated

Although no generic fingolimod is currently marketed in China, Huahai’s fingolimod received tentative approval from the U.S. FDA in 2017, making its domestic launch a straightforward endeavor. Consequently, once fingolimod is launched in China, it will face not only competition from drugs in the same class but also significant pressure from generic alternatives.

Original Title: Hot Topic | A Bombshell Hits the Domestic Multiple Sclerosis Field! Novartis' Fingolimod, with Annual Sales Exceeding RMB 3 Billion, Is Set to Launch in China