Novartis' Siponimod for Multiple Sclerosis Set for China Approval Just One Year After U.S. Launch

Text | Cai Cai

Recently, the marketing application for Novartis’ siponimod tablets (acceptance numbers: JXHS1900028 and JXHS1900029) has been updated to “under review,” with approval expected in the near future. Siponimod is a medication used to treat multiple sclerosis (MS). It received FDA approval in March 2019. In July 2019, Novartis’ another blockbuster MS drug, fingolimod, was launched in China.

(Source: NMPA)

Approved by the FDA in March 2019

Siponimod (brand name: Mayzent) is a next-generation selective sphingosine-1-phosphate (S1P) receptor modulator developed by Novartis. It binds to the S1P1 receptor subtype on lymphocytes, preventing their entry into the central nervous system (CNS) of patients with multiple sclerosis (MS), thereby exerting an anti-inflammatory effect.

Studies have shown that siponimod tablets can prevent neurodegenerative changes in neuronal synapses and promote myelin regeneration in the central nervous system (CNS). It has the potential to modify the course of the disease. In March 2019, it was approved by the U.S. FDA for marketing as an oral tablet, available in two strengths: 0.25 mg and 2 mg. It is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), including relapsing-remitting disease and active secondary progressive multiple sclerosis (active SPMS).

In February 2019, the Center for Drug Evaluation (CDE) accepted the marketing application for siponimod tablets, which was subsequently included in the priority review program. Its recent approval came just one year after its approval in the United States. In May 2018, multiple sclerosis (MS) was included in China’s “First Batch of Rare Diseases Catalogue.” The approval of siponimod is expected to provide new treatment options for this patient population.

The latest data on siponimod tablets have been published in the April 2020 supplement of Neurology, the medical journal of the American Academy of Neurology. These data build upon existing clinical evidence demonstrating that Mayzent slows the progression of limb disability and provides cognitive benefits in patients with secondary progressive multiple sclerosis (SPMS). The newly published data from the 5-year EXPAND open-label extension trial evaluated the long-term efficacy and safety of Mayzent in patients with SPMS. The results showed that, compared with the placebo switch group, patients in the Mayzent group had a significantly reduced likelihood of confirmed disability progression (CDP) at 3 months and 6 months (p=0.0064 and p=0.0048, respectively), highlighting the advantages of early treatment. The new data also revealed a 52% reduction in the annualized relapse rate (ARR) in the Mayzent group compared with the placebo switch group (p<0.0001). Furthermore, the risk of confirmed worsening of cognitive impairment at 6 months, as assessed by the Symbol Digit Modalities Test, was reduced by 23% in the Mayzent group compared with the placebo switch group (p=0.0014). These clinical benefits observed in the Mayzent group were sustained over 5 years, underscoring the advantages of early treatment.

High R&D Interest: Best-Selling Drug Achieves Annual Sales of Up to $4.4 Billion

Multiple Sclerosis (MS) is a chronic, immune-mediated inflammatory demyelinating disease of the central nervous system. It commonly affects the periventricular regions, juxtacortical areas, optic nerves, spinal cord, brainstem, and cerebellum. The lesions are characterized by dissemination in space and time. The incidence and prevalence of MS are correlated with geographic distribution and ethnicity. High-prevalence regions include Europe, southern Canada, North America, New Zealand, and southeastern Australia, where the incidence ranges from 60/100,000 to 300/100,000. In contrast, Asian and African countries have a lower incidence, approximately 5/100,000. China is considered a low-incidence region, with an incidence rate likely similar to that of Japan.

MS - Chronic Inflammatory Demyelinating Disease of the Central Nervous System

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

(Compiled from publicly available sources)

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

The 2019 edition of the "Guidelines for Diagnosis and Treatment of Rare Diseases" issued in China recommends 13 internationally recognized medications, such as interferon (injection), glatiramer acetate (injection), fingolimod (oral), teriflunomide (oral), dimethyl fumarate (oral), natalizumab (injection), alemtuzumab (injection), ocrelizumab (injection), and mitoxantrone (injection). Among these, interferon (IFNβ) and glatiramer acetate (brand name: Copaxone) are first-line treatments for relapsing-remitting multiple sclerosis (MS), administered via subcutaneous or intramuscular injection. Natalizumab (brand name: Tysabri) and mitoxantrone (brand name: Novantrone) are primarily used as second-line therapies and require intravenous infusion under the supervision of professional healthcare personnel.

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

Between 2010 and 2020, six drugs were launched, targeting Nrf2, S1P receptors, and CD20. Among them, dimethyl fumarate achieved the highest sales, with global revenue reaching $4.44 billion in 2019, representing a year-on-year increase of 4.0%.

MS Therapeutics Approved Globally Between 2010 and 2020

(Source: Company Annual Report)