Bimzelx indication expanded to inflammatory diseases

Indications expanded to include psoriatic arthritis and hidradenitis suppurativa… strengths of new mechanisms highlighted

TYK2 and JAK inhibitors join the race, accelerating diversification of treatment options for inflammatory diseases

The inflammatory disease treatment market, which had long been dominated by biologics such as Humira (adalimumab) and Cosentyx (secukinumab), is showing signs of significant change. Competition is intensifying as not only biologics but also Janus kinase (JAK) inhibitors and next-generation targeted therapies are successively expanding their indications.

UCB Pharma's ‘Bimzelx’

According to industry sources on the 30th, the Ministry of Food and Drug Safety (MFDS) has approved Bimzelx (bimekizumab) for 3 additional indications: ▲psoriatic arthritis, ▲axial spondyloarthritis, and ▲hidradenitis suppurativa.

Bimzelx is the first and only biologic that simultaneously inhibits interleukin-17A and interleukin-17F. It received its initial domestic approval in August last year for the treatment of plaque psoriasis.

This approval for psoriatic arthritis is based on results from two Phase III clinical trials: the BE OPTIMAL study in biologic-naive patients and the BE COMPLETE study in patients who had inadequate response or intolerance to TNF-α inhibitors.

In the BE OPTIMAL study, 44% of the Bimzelx group achieved the primary endpoint of ACR50 at week 16, showing a significant improvement compared to the placebo group (10%). In the BE COMPLETE study, 43% of the Bimzelx group achieved ACR50, and 27% achieved ACR70. No new safety signals were observed in either study.

The axial spondyloarthritis indication was approved based on the results of two parallel Phase III clinical trials: BE MOBILE 1 in non-radiographic patients and BE MOBILE 2 in radiographic patients.

In the studies, the 16-week ASAS40 response rates in the Bimzelx group were 48% and 45%, respectively, significantly higher than in the placebo group (21% and 23%). Responses were observed within 1 to 2 weeks after the first dose, and the response rate continued to increase through week 24. Patients who switched from placebo to Bimzelx also showed similar response rates at week 24. No new adverse reactions were identified in terms of safety.

The hidradenitis suppurativa indication was approved based on two Phase III clinical trials, BE HEARD 1 and 2, conducted in moderate-to-severe patients. The proportion achieving HiSCR50 at week 16 was 48% and 52% in the Bimzelx groups, respectively, significantly higher than the placebo groups (29%, 32%).

The more stringent HiSCR75 responses were also higher in the Bimzelx group at 33% and 36%, respectively, compared to placebo. These benefits were maintained or further improved through 48 weeks, with meaningful improvements observed in quality-of-life measures such as DLQI. An integrated long-term extension analysis confirmed sustained efficacy and safety over two years.

New competitors enter the field… Potential of TYK2-targeted novel drugs draws attention

With the expansion of Bimzelx’s indications, competition with existing biologics and JAK inhibitors has become inevitable. Current competitors with overlapping indications include major biologics and JAK inhibitors like Novartis’s Cosentyx, AbbVie’s Humira and Rinvoq (upadacitinib), and Johnson&Johnson’s Stelara (ustekinumab).

BMS’s ‘Sotyktu’

The rapid advancement of new TYK2 inhibitors is also noteworthy. Currently, BMS's ‘Sotyktu (deucravacitinib)’ has only secured approval for plaque psoriasis in Korea. BMS has completed clinical trials for psoriatic arthritis and is awaiting regulatory review in the US.

Unlike JAK inhibitors, TYK2 inhibitors selectively suppress the TYK2 protein, blocking only signaling in the IL-12, IL-23, and Type I interferon pathways. This allows for safer treatment while regulating immune responses, making them a point of interest.

Among existing biologics, IL-17 inhibitors have faced concerns about exacerbating inflammatory bowel diseases like ulcerative colitis or Crohn's disease and causing oral candidiasis. While IL-23 inhibitors showed no prominent adverse reactions, concerns exist regarding injection site pain or discomfort and upper respiratory tract infections. This is one reason new treatment options are gaining attention.

Competition among latecomers is also inevitable.

Takeda’s zasocitinib is regarded as one of the most advanced TYK2 inhibitors following Sotyktu. Its commercial potential was confirmed in a Phase IIb clinical trial published last year in the medical journal JAMA.

This study randomly assigned 259 participants to receive one of four daily oral doses of zasocitinib (2mg, 5mg, 15mg, or 30mg) or placebo for 12 weeks.

Clinical results showed a dose-dependent response to zasocitinib. The proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 (75% or greater improvement in skin condition) was 18%, 44%, 68%, and 67% in the respective dose groups, significantly higher than the 6% in the placebo group. Furthermore, no serious safety concerns were reported in this study, indicating that zasocitinib has a favorable safety profile.

Takeda is actively developing zasocitinib for indications beyond psoriasis and is also pursuing approval for psoriatic arthritis. Furthermore, Takeda is conducting Phase II studies for moderate-to-severe active Crohn's disease and ulcerative colitis, and is planning studies for systemic lupus erythematosus, exploring the potential of zasocitinib in other immune-mediated diseases.