Multiple sclerosis saves the fate of CD20 antibodies

Author | Leaf

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination of the central nervous system [1-2]

At present, the treatment of MS covers multiple disciplines and methods, including disease modification therapy (DMT), symptomatic treatment, life>

However, in the face of low-cost generic drugs and convenient oral innovative drugs, the CD20 antibody drug Ocrevus for injection developed by Roche has become the best-selling MS drug in a short period of time.

After rituximab, CD20 tumor-targeted drugs are no longer strong

CD20 is a 33-37 kDa non-glycosylated quadruple transmembrane protein, encoded by the MS4A1 gene, with intracellular N-terminal and C-terminal regions and two extracellular loops usually called small and large loops.

References [5]

Rituximab is a chimeric mouse/human monoclonal antibody therapy and the first CD20 antibody approved for marketing.

After rituximab, CD20 antibody has developed to the third generation along with the development concepts of humanization/fully humanization and modification of the Fc region to enhance activity

Otuzumab is a CD20 antibody obtained by glycosylation (defucosylation) of rituximab.

Representative CD20 antibody drugs approved

Several other CD20 antibodies that use tumors as the first indication have also had a poor record.

Therefore, although Gazyva (Otuzumab) is an upgraded product of rituximab, it is inevitable that the market competition environment is different from that of Rituxan.

So, what hope is there for CD20 antibodies? Based on the mechanism by which B cells and their secreted cytokines exacerbate the development of multiple sclerosis disease, is it the right choice for CD20 antibodies to turn to MS disease development?

Drugs and mechanisms related to multiple sclerosis disease mitigation therapy (Reference [5])

Multiple sclerosis saves CD20 antibody from critical path

Roche has developed three CD20 products based on the strategy of technological iteration.

Roche CD20 antibody global sales (unit: million Swiss francs)

According to the data disclosed in the 2020 financial reports of various companies, Ocrevus is already the MS treatment drug with the highest sales

2020 MS drug sales TOP5 (100 million U.

Source: NextPharma

Ocrevus stands out in the MS field for many reasons

Source: NextPharma

Secondly, when Ocrevus was first approved, it also covered the primary progressive multiple sclerosis (PPMS) patient population.

Judging from the current form of market competition in the MS field, Tecfidera (dimethyl fumarate) was swallowed by generic drugs, and sales fell severely; Gilenya (Fingolimod) encountered similar new products Mayzent (Siniimod) and Zeposia ( Ozamod) and Ponvory (ponesimod) compete for the market, and the decline in market share is inevitable.

For example, Novartis launched Arzerra (ofatumumab) in 2009 as a tumor indication and expanded to the field of MS in 2020.

Generally speaking, Ocrevus and Arzerra have their own advantages, and how much market share they can get in the MS field depends on their own abilities
.
However, for CD20 antibody drugs, its originally dim commercial fate is undoubtedly rescued by the disease of MS
.
Looking back, the development of Roche's three CD20 iteration products has also condensed the development history of CD20 drugs, and different market conditions have interpreted the strategy and strategic importance of the company in the development of innovative drugs
.
We will wait and see how exciting other CD20 antibodies will be
.

Reference

[1] Sun Mengying, et al.
Progress in the pathogenesis of multiple sclerosis.
Chinese Journal of Traditional Chinese Medicine, 2021, 36(3): 1533-1538

[2] Diagnosis and Treatment of Multiple Sclerosis.
JAMA, 2021, 325(8): 765-779

[3] Jia Yan, et al.
Progress in multiple sclerosis research.
Journal of Medical Forum, 2020, 41(7): 170-173

[4] Jia Chunying, et al.
Progress in the diagnosis and treatment of multiple sclerosis.
International Journal of Pediatrics, 2019, 46(11): 785-789

[5]Timothy Pierpont, Candice Limper, Kristy Richards.
Past, Present, and Future of Rituximab—The World's First Oncology Monoclonal Antibody Therapy.
https://doi.
org/10.
3389/fonc.
2018.
00163