Although global sales will exceed US$20 billion in 2023, the market ceiling for IL-23 inhibitors seems to be far from coming. The expansion of new indications remains the key to continued sales growth.

Since 2023, Eli Lilly’s Mirikizumab, AbbVie’s Skyrizi and Johnson & Johnson’s Tremfya have been approved for UC (ulcerative colitis) indications and have quickly entered this market. According to a report released by Spherix Global Insights, IL-23 inhibitors have gained significant development momentum since their entry in 2023 and have occupied one-tenth of the UC market share in 2024. The above figures confirm the predictability of IL-23 inhibitors in the UC market. After all, in the highly competitive UC market, such growth is rare.

But at the same time, as the number of competitors increases, different IL-23 inhibitor markets also need to worry about market share in the UC market. The competition has quietly begun. It is not only a collision of strength, but also a competition of strategies. Their next choices and actions will not only be related to the quality of their position, but also their life and death.

For big pharmaceutical companies, UC seems to be a battleground, which is related to several core factors. First, there is the urgent need for disease treatment. In ulcerative colitis, which is localized to the colon, the mucosal layer becomes inflamed, causing superficial damage to the intestinal wall. Although a chronic disease of the gastrointestinal tract that does little harm in the short term, the disease can ebb and flow, and episodes often cause more severe symptoms: such as having to go to the bathroom very frequently, as well as stomach and joint pain, which can be extremely affecting. Quality of life requires effective and ongoing treatment.

Secondly, there is a huge demand for treatment. In 2023, the global prevalence of ulcerative colitis is estimated to be 5 million cases, and the global incidence rate is on the rise, especially in developing countries represented by China. This also means that the overall demand for treatment is very large.

In addition, there is an ongoing need for treatment. Due to the complex causes of UC and the lack of accurate answers to its pathogenesis, the disease has always lacked an effective cure and can only provide relief. Therefore, life-long treatment is required, which is divided into two stages: initial induction therapy and subsequent maintenance therapy. Of particular note is the fact that ulcerative colitis is typically diagnosed in younger people and patients are on medication for a relatively long period of time.

For this reason, since the end of the last century, biological agents represented by adalimumab have become a new treatment option in the field of UC, which has greatly improved the quality of life of patients and allowed pharmaceutical companies to obtain corresponding generous returns. However, at present, there are far from enough effective treatments in the field of UC:
On the one hand, the response rate is not high. Data show that the response rate in induction clinical trials does not exceed 20-30%, and in real life the response rate does not exceed 30-60%. On the other hand, among patients who are effective in initial treatment , and about one-half of patients will develop a "secondary loss of response" phenomenon, which is similar to antibiotic "resistance."

The huge unmet clinical needs highlight the importance of continuing to develop new treatments for UC, so pharmaceutical companies are still betting on this market. It is in this context that IL-23 inhibitors have achieved sudden emergence, driven by their good reputation. In the world of innovative medicines, results are king. The three giant IL-23 inhibitors have been quickly recognized in the UC market because of their outstanding clinical effects.

On the one hand, they can fill needs that cannot be met by existing therapies. Mirikizumab is the first IL-23 inhibitor approved for use in the U.S. market. It is used to treat patients with moderate to severe UC who have insufficient response, loss, or intolerance to conventional therapies (hormones, biological agents, etc.). This is due to its outstanding clinical data. Data from the phase III trial showed that in the above-mentioned groups, mirikizumab achieved the primary endpoint of clinical response in 24.2% of patients at week 12, compared with 13.3% in the placebo group, and the effect increased over time, at week 40. The response rate was 49.9%, compared with 25.1% in the placebo group.

Furthermore, mirikizumab led to histological endoscopic response and achieved relief of bowel urgency in patients with moderate to severe UC compared with placebo, so the results were excellent. Not only Mirikizumab, but also Risankizumab and Guselkumab have also shown that they can still have satisfactory therapeutic effects in patient groups that cannot be touched by existing therapies or continue to progress. It is precisely for this reason that IL-23 inhibitors can gain an important position in the UC market.

IL-23 inhibitors, on the other hand, seem to do better. According to some meta-analyses, IL-23 inhibitor treatment is more effective in patients with moderate to severe ulcerative colitis compared with traditional methods such as adalimumab and infliximab. Overseas, the medical community has been paying close attention to the progress of IL-23 inhibitors in the treatment of UC. J&J's Tremfya "had a strong debut" and the "vast majority" of gastroenterologists were aware of its approval, according to a Spherix Global Insights report that spoke to more than 100 doctors.

Therefore, it seems reasonable that IL-23 inhibitors can quickly gain a considerable market share in the UC market, and it is bound to continue in the future.

Of course, as more and more IL-23 inhibitors are approved for UC indications, competition will become increasingly fierce. This also requires pharmaceutical companies to create high enough recognition for their IL-23 inhibitors. A Spherix Global Insights report shows that most gastroenterologists already view IL-23 drugs as clinically differentiating, with Skyrizi becoming the first choice. The core reason is that AbbVie's Skyrizi differentiates itself from rivals through its body-worn injector device and its early approval for Crohn's disease. Because of these advantages, doctors gained valuable experience with the drug before approving it for UC.

Based on this, overseas pharmaceutical companies still hope to create differentiation to win a higher market share. For example, the core selling point of Eli Lilly's Mirikizumab is the improvement of bowel urgency. It is not difficult to understand that in 2019, the American College of Gastroenterology proposed new definitions of mild, moderate and severe active UC. Urgency to defecate is considered an important symptom that needs to be evaluated and is included in the UC disease activity index.

Mirikizumab has been shown to alleviate defecation urgency in clinical trials, which will naturally become the key to attracting the market. Johnson & Johnson's promotion of Tremfya is a "dual mechanism." Tremfya not only binds to IL-23 but also to CD64, a receptor on cells that produce IL-23, theoretically producing better relief.

For this reason, in the UC market, IL-23 inhibitors are not only a collision of strength, but also a competition of strategies. In the future, the market size of IL-23 inhibitors in ulcerative colitis will still grow, but we need to continue to observe who can ultimately capture more market share.

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