Janssen's Guselkumab Receives NMPA Approval for Moderately to Severely Active Crohn’s Disease

Recently, Johnson & Johnson has achieved a significant breakthrough in the pharmaceutical field: its Guselkumab Injection has successfully obtained approval from the NMPA for the treatment of adult patients with moderate to severe active Crohn's disease who have had an inadequate response to, lost response to, or were intolerant to conventional therapies or biologics.

World's First Batch

Crohn's Disease, as one of the two main subtypes of inflammatory bowel disease, severely impacts the health of millions of people worldwide. Over the past few decades, the incidence of Crohn's Disease in China has been on a continuous rise, with an annual incidence rate of approximately 0.51-1.09 per 100,000 people, and the peak age of onset is concentrated between 20 to 30 years old.

Traditionally, the treatment of Crohn's disease mainly includes medication and surgical treatment. In terms of medication, commonly used drugs include aminosalicylates, glucocorticoids, immunosuppressants, and biologics, among others. However, these drugs often have issues such as limited efficacy, significant side effects, or high treatment costs. For example, while glucocorticoids can quickly alleviate symptoms, long-term use can lead to serious side effects like osteoporosis, hypertension, and diabetes. Although immunosuppressants can reduce the recurrence of the disease, they take longer to become effective and carry risks such as infection. Biologics, such as anti-TNF-α antibodies, have improved treatment outcomes to a certain extent, but some patients show poor response to the treatment or develop drug resistance.

Surgical treatment is another therapeutic approach for Crohn's disease, but surgery cannot cure the disease and has a high postoperative recurrence rate. In addition, surgery may lead to a series of complications such as short bowel syndrome, intestinal fistulas, and abdominal pain. Therefore, finding a safe, effective, and long-term method to control disease progression has always been a key focus in Crohn’s disease research.

In recent years, with the in-depth research on the pathogenesis of Crohn's disease, scientists have gradually recognized the crucial role of the immune system in the onset and development of the disease. In particular, the abnormal activation of the IL-23 pathway in Crohn's disease is considered an important factor leading to the persistence of intestinal inflammation. Therefore, targeted therapy against the IL-23 pathway has become a new direction for the treatment of Crohn's disease.

Guselkumab is a specific anti-IL-23 monoclonal antibody. The global approval of this drug for moderate to severe active adult Crohn's disease is of great significance. It provides a new treatment option for patients who have had unsatisfactory results with conventional treatments or biologic agents, adding new momentum to the field of Crohn's disease treatment.

Unique IL-23 Inhibitor

In the human immune system, IL-23 is crucial. It is a pro-inflammatory cytokine composed of the p19 and p40 subunits. Although it shares the p40 subunit with IL-12, there are significant differences in receptor specificity and biological functions. IL-12 plays a key mediating role by promoting the differentiation and development of Th1 cells, which in turn induces the production of IFN-γ. On the other hand, IL-23 actively participates in the differentiation process of Th17 cells under conditions where TGF-β and IL-6 are both present. IL-23 binds to cell surface receptor complexes, activating intracellular Jak2 and Tyk2 proteins, leading to the phosphorylation of the receptor complex and creating STAT protein binding sites. Subsequently, STAT proteins are phosphorylated, dimerized, and translocated to the nucleus, activating relevant target genes and triggering a cascade of cytokine reactions, thereby activating immune cells to initiate immune responses.

Under physiological conditions, this serves as a defense barrier against pathogens. However, in patients with autoimmune diseases, the immune response is excessively activated, leading to sustained high expression of IL-23. The immune system attacks the body's own tissues, triggering inflammation, such as in the gastrointestinal tract of Crohn's disease patients. IL-23 inhibitors block the IL-23 cytokine, prevent its binding to receptors, and interrupt downstream inflammatory signaling pathways, restoring immune system homeostasis and alleviating inflammatory symptoms.

Guselkumab, as a fully human interleukin-23 inhibitor, possesses a unique dual mechanism of action. First, it can bind with high affinity to the p19 subunit of IL-23, precisely blocking the interaction between IL-23 and its receptor. Second, it is also able to modulate immune cell activity in a specific manner, inhibiting inflammatory responses from multiple dimensions. This dual mechanism acts like a double "insurance" for uncontrolled inflammatory reactions, demonstrating significant advantages in the treatment of autoimmune diseases.

In the treatment of Crohn's disease, the advantages of Guselkumab are fully demonstrated. According to clinical data from two pivotal Phase III studies (GALAXI2 and GALAXI3) in the GALAXI research program, Guselkumab has shown superior efficacy across multiple key indicators. In terms of clinical remission rates, patients treated with Guselkumab achieved significantly higher remission rates compared to traditional treatment groups or biologic control groups. After a certain course of treatment, many patients experienced significant improvement in symptoms such as abdominal pain and diarrhea, leading to a notable enhancement in quality of life. In terms of deep remission rates, Guselkumab also performed exceptionally well, with more patients achieving deep remission of intestinal inflammation. Endoscopic examination results showed significant repair of inflammation and damage to the intestinal mucosa.

Guselkumab is also the only IL-23 inhibitor that has demonstrated superiority over Stelara (ustekinumab) across multiple endoscopic endpoints in a double-blind head-to-head registrational clinical trial (GALAXI).

Focusing on the autoimmune track

With the increasing emphasis on health and the deepening research into the pathogenesis of autoimmune diseases, the global market for autoimmune disease drugs has shown vigorous growth in recent years, becoming the next significant market after oncology drugs. Predictive data indicates that by 2030, the global market size for autoimmune disease drugs is expected to reach 176.7 billion US dollars, of which the biologics market will reach 145 billion US dollars, accounting for 82.1%.

Such a huge market pie has attracted fierce competition from numerous pharmaceutical companies. AbbVie holds a significant position in the autoimmune field with products like risankizumab and adalimumab; Sanofi's dupilumab, with its expanding indications, has become the new "king of autoimmune" globally; Novartis' secukinumab has achieved remarkable success in psoriasis treatment by successfully outperforming many competitors through a series of "head-to-head" clinical trials. In the niche track of inflammatory bowel disease, Takeda’s vedolizumab, an α4β7 monoclonal antibody, made an early bet and has now become the best-selling biologic in this category. Many pharmaceutical companies are increasing R&D investment, continuously launching new products and treatment solutions through self-research, mergers and acquisitions, collaborations, and other methods, attempting to secure a place in this promising market.

Johnson & Johnson, as a giant in the pharmaceuticals industry, has a profound and comprehensive layout in the autoimmune field. Over the years, Johnson & Johnson has continuously invested substantial resources into research and development, constantly introducing innovative drugs and leading the transformation in autoimmune disease treatment. Its drug, infliximab, was the first antibody drug discovered to have therapeutic effects in autoimmune diseases. It was approved for marketing in 1998 for inducing remission in moderately to severely active Crohn's disease and fistulizing Crohn's disease. Subsequently, it achieved clinical success and gained approval across multiple indications, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, and plaque psoriasis. Over the 25 years since its market launch, it has contributed over $900 billion in cumulative revenue to Johnson & Johnson.

# Ustekinumab: A Star Autoimmune Product from Johnson & JohnsonAs an IL-12/IL-23 dual-target inhibitor, ustekinumab boasts a groundbreaking mechanism of action, with its uniqueness being self-evident. Additionally, the dosing regimen, which requires only one subcutaneous injection every three months, greatly enhances convenience for patients. With these advantages, ustekinumab has quickly risen to prominence in the autoimmune field. In 2023, its sales achieved a major breakthrough, surpassing the $10 billion threshold for the first time, reaching an impressive $10.858 billion. Even in 2024, despite facing market competition from biosimilars and experiencing a decline in sales, it still maintained a strong position at $10.361 billion, demonstrating robust market competitiveness. Golimumab, administered via subcutaneous injection once a month, improves patient compliance and has become a blockbuster product with annual sales exceeding $2 billion.

This time, the approval of Guselkumab for the treatment of Crohn's disease has further enriched Johnson & Johnson's product line in the autoimmune field. It not only provides Johnson & Johnson with a more powerful weapon in the field of inflammatory bowel disease treatment but also is expected to leverage the company’s strong market promotion capabilities and sales network to quickly capture a significant market share, further solidifying Johnson & Johnson's position in the autoimmune sector. In addition to its marketed products, Johnson & Johnson is actively expanding its R&D pipeline in the autoimmune field. The oral interleukin-23 receptor (IL-23R) antagonist Icotrokinra (JNJ-2113), developed by the company, achieved positive pivotal results in the Phase III ICONIC-LEAD study for treating patients aged 12 years and older with moderate to severe plaque psoriasis, demonstrating substantial market potential.

Conclusion

Johnson & Johnson's Guselkumab Approved for Treatment of Crohn's Disease: A Significant Milestone in Autoimmune Field Offers New Treatment Opportunities for Patients and Boosts the Development of Autoimmune Sector.

Source: Johnson & Johnson official website, NMPA

Editor: Liuli

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