Novartis' Ofatumumab NDA for Relapsing Multiple Sclerosis Included in CDE Priority Review

On November 23, according to the official website of the Center for Drug Evaluation (CDE), Novartis’s CD20 monoclonal antibody ofatumumab’s marketing application (JXSS2000049) was included in the list of drugs proposed for priority review. The proposed indication is relapsing multiple sclerosis (RMS) in adults, including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS), marking another step closer to its approval and market launch in China.

Ofatumumab is a fully human monoclonal antibody targeting CD20-positive B cells, developed by Genmab. In 2006, global commercial rights were granted to GSK. In October 2009, the drug was approved by the FDA under the brand name Arzerra for first-line treatment, in combination with chlorambucil, of patients with previously untreated chronic lymphocytic leukemia (CLL) who are not suitable for fludarabine-based therapy. Subsequently, it was also approved for extended treatment of patients with relapsed or progressive CLL who had achieved complete or partial response after at least two prior lines of therapy, as well as for use in combination with fludarabine and cyclophosphamide in patients with relapsed CLL.

In 2015, Novartis paid $1 billion to acquire the commercial rights to ofatumumab from GSK, assigning it a new development code, OMB157, for its development as a next-generation B-cell depleting agent. In August 2020, ofatumumab was approved by the FDA for the treatment of relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome in adults, relapsing-remitting disease, and active secondary progressive disease, under the brand name Kesimpta.

Multiple Sclerosis (MS) is a severe, lifelong, progressive, and disabling demyelinating disease of the central nervous system. It primarily manifests as muscle weakness, fatigue, pain, cognitive impairment, and visual problems, and has become a leading cause of non-traumatic disability. The disease predominantly affects young adults aged 20–40 years, with women accounting for approximately two-thirds of cases. Statistics indicate that there are over 20 million MS patients worldwide, while more than 30,000 patients have been diagnosed in China.

Based on the disease course, multiple sclerosis (MS) can be classified into four types: relapsing-remitting MS (RRMS, accounting for approximately 85%), secondary progressive MS (SPMS, with about 80% of RRMS cases progressing to SPMS), primary progressive MS (PPMS, accounting for approximately 10%), and progressive-relapsing MS (PRMS, accounting for approximately 5%). Treatment decisions vary by subtype, and currently approved medications are primarily targeted at RRMS.

According to the Insight database, multiple multiple sclerosis (MS) drugs have currently been approved in China, namely recombinant human interferon beta-1a, recombinant human interferon beta-1b, teriflunomide (Sanofi), fingolimod (Novartis), and siponimod (Novartis). Among these, teriflunomide is approved for relapsing forms of MS (RMS); fingolimod is approved for active secondary progressive MS (PRMS); and siponimod is approved for RMS, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS). However, both teriflunomide and fingolimod face threats from generic competition, with marketing applications for generic versions already submitted by pharmaceutical companies.

Novartis’ application for market approval of ofatumumab for the treatment of relapsing multiple sclerosis (RMS) has been included in the Center for Drug Evaluation’s (CDE) proposed priority review list. This is expected to accelerate its approval and launch in China, further strengthening Novartis’ position in the multiple sclerosis (MS) market. Based on 2019 corporate sales revenue for MS drugs, Biogen, Roche, and Novartis ranked as the top three players, respectively. However, with patent expirations, drugs such as dimethyl fumarate, fingolimod, and teriflunomide are all facing competition from generic alternatives, making the future competitive landscape of the MS market uncertain.

For Novartis, the market for fingolimod began to shrink, with sales declining from $3.341 billion in 2018 to $3.223 billion in 2019. Due to its later approval (FDA: March 2019; NMPA: May 2020), siponimod generated only $26 million in sales in 2019. With ofatumumab approved in the United States for the treatment of multiple sclerosis (MS) and its marketing application submitted in China, Novartis is expected to reverse its downward trend in the MS market and even achieve surpassing growth as the scope of approvals expands in the future.

Moreover, it is worth noting that Kesimpta (ofatumumab) is the first B-cell-targeted therapy that allows patients to self-administer a monthly subcutaneous injection at home using the Sensoready autoinjector pen. Data from its approved clinical trials, ASCLEPIOS I and ASCLEPIOS II, demonstrate that Kesimpta offers advantages over teriflunomide in significantly reducing the annualized relapse rate (ARR, the primary endpoint), 3-month confirmed disability progression (CDP), gadolinium-enhancing (Gd+) T1 lesions, and the number of new or enlarging T2 lesions, positioning it as a preferred treatment option for patients with relapsing multiple sclerosis (RMS). Regulatory approvals for Kesimpta are currently underway in other countries worldwide, with approval in Europe anticipated before the second quarter of 2021.