Janssen Submits Guselkumab (Tremfya) for Approval in China Amid Heated Psoriasis Market Competition

Original: Cai Cai

Recently, Johnson & Johnson’s guselkumab (brand name: Tremfya) has filed for marketing approval in China. Guselkumab has earned the title of “best psoriasis drug” due to its superior efficacy over adalimumab and secukinumab in head-to-head trials. With 2018 sales reaching $544 million, it is beginning to demonstrate the potential of a blockbuster drug.

As of now, three blockbuster drugs have been launched this year: Johnson & Johnson’s ustekinumab (brand name: Stelara), Novartis’ secukinumab (brand name: Cosentyx), and the domestically produced benvitimod. The competition in China’s psoriasis market is becoming increasingly intense.

Head-to-head victory over adalimumab and secukinumab

Guselkumab was approved by the FDA for marketing on July 13, 2017, for the treatment of moderate-to-severe plaque psoriasis in adults.

Guselkumab is the world’s first approved anti–IL-23 monoclonal antibody, administered as an initial dose at weeks 0 and 4, followed by 100 mg subcutaneously every 8 weeks.

In the VOYAGE 1 and VOYAGE 2 studies, guselkumab treatment achieved >90% skin clearance in 70% of patients at Week 16, with over 90% of patients achieving PASI 90 by Week 28, and response was maintained through Week 48. In head-to-head studies against adalimumab, the guselkumab group demonstrated superior skin clearance compared to adalimumab at Weeks 16, 24, and 48.

In the head-to-head ECLIPSE Phase III study, 48-week results of guselkumab versus secukinumab for the treatment of moderate-to-severe plaque psoriasis showed that the proportion of patients achieving a ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90, primary endpoint) was 84.5% in the guselkumab group, compared with 70% in the secukinumab group.

Biologics Become a Hotspot in R&D

Psoriasis (Psoriasis) is a common, chronic, non-contagious, painful, disfiguring, and disabling immune-mediated inflammatory disease, classified as an autoimmune chronic skin condition. Up to 125 million people worldwide are affected by psoriasis. In terms of global prevalence by country, it is most common among populations in Northern Europe and Australia, less common in East Asian populations, with approximately 6 million patients in China.

Psoriasis is primarily classified into four major types: plaque psoriasis (including plaque, guttate, and inverse subtypes), pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis. Plaque psoriasis accounts for more than 90% of all psoriasis cases. The etiology is complex; it is currently believed that T-cell dysregulation leads to excessive proliferation of keratinocytes and altered terminal differentiation, resulting in a less cohesive stratum corneum and the characteristic plaques of psoriasis. Both genetic and environmental factors induce keratinocytes to secrete tumor necrosis factor (TNF), which further activates dendritic cells (DCs). Activated DCs produce interleukin-23 (IL-23), driving the differentiation of T helper 17 (Th17) cells. Th17 cells secrete IL-17A, leading to the pathological skin changes observed in psoriasis. Therefore, TNF-α, IL-23, and IL-17A are considered key therapeutic targets for the treatment of moderate-to-severe plaque psoriasis.

The treatment of psoriasis is divided into pharmacological and non-pharmacological therapies. Pharmacological therapies include topical agents, systemic medications, traditional Chinese medicine (TCM), and biologics, while non-pharmacological therapies encompass physical therapy, hydrotherapy, dietary intervention, and psychological therapy.

Biologics represent a novel therapeutic arsenal for psoriasis and mark another major advancement in the history of psoriasis treatment; however, they are associated with high costs and potential adverse reactions. Currently, biologics for psoriasis are categorized into two main classes: one comprising agents with broader indications, such as adalimumab, etanercept, and infliximab; and the other consisting of mainstream agents, such as ustekinumab and secukinumab.

Mainstream Drugs for the Treatment of Psoriasis Currently Available on the Global Market

(Compiled based on public information; please feel free to add any missing details.)

It should be explicitly noted that apremilast is a small-molecule phosphodiesterase-4 (PDE-4) inhibitor, not a biologic agent. The drug was approved by the FDA in 2014 for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for phototherapy or systemic therapy. The author includes it in the table because apremilast significantly inhibits epidermal cell proliferation, reduces epidermal thickness, and decreases the expression of human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecules in psoriatic lesions, thereby alleviating psoriasis symptoms. Its annual sales exceed $1 billion.

Domestic Class 1 Innovative Drug Benvitimod Launched

In addition to biologics, other drugs have also shone brightly.

On May 31, 2019, the National Medical Products Administration (NMPA) approved the marketing of Benvitimod Cream, a Class 1 innovative drug, through the priority review and approval process. It is indicated for the topical treatment of mild-to-moderate stable plaque psoriasis in adults. Benvitimod (formerly known as Benximod) is a tyrosine protein kinase inhibitor that exerts its therapeutic effects by inhibiting T-cell tyrosine protein kinases, thereby interfering with or blocking the release of cytokines and inflammatory mediators, T-cell migration, and skin cell activation. The launch of Benvitimod Cream provides a new pharmacological treatment option for adult patients with mild-to-moderate stable plaque psoriasis.

A Highly "Lucrative" Field

Although multiple drugs have been approved for the treatment of psoriasis, the condition remains incurable, with existing medications only alleviating symptoms. Consequently, the psoriasis drug market represents a highly lucrative sector. There are approximately 8 million psoriasis patients in China, a number that is increasing year by year. IMS data projects that the global market for psoriasis therapeutics will reach $9.02 billion in 2019, while a research report from Southwest Securities indicates that the domestic psoriasis market exceeds RMB 3 billion.

Global Market Size of Major Psoriasis Drugs

Notably, Hengrui also has a psoriasis drug, SHR-1314, which is a recombinant humanized monoclonal antibody targeting human IL-17A.

Currently in Phase I clinical trials.