▎WuXiEdited by Kant Content Team

Recently, Johnson & Johnson announced the first Phase 3 trial results of its IL-23-targeted antibody Tremfya (guselkumab) in adult patients with moderate to severe active Crohn's disease (CD). The analysis shows,Compared with placebo and the IL-12/IL-23 inhibitor Stelara (ustekinumab), both doses of Tremfya demonstrated superiority.According to the press release, the GALAXI study announced this time is the first double-blind, registrational head-to-head clinical trial showing that Tremfya is more effective than Stelara in treating CD patients.

Crohn's disease is a chronic systemic condition characterized by inflammation in the gastrointestinal or digestive tract, which, during flare-ups, causes persistent diarrhea, abdominal pain, and rectal bleeding.It is a progressive disease that worsens over time. Due to the unpredictable symptoms of Crohn's disease, it imposes multiple burdens on patients physically, emotionally, and financially.

GALAXI is a randomized, double-blind, placebo- and active-controlled global, multicenter Phase 2/3 study designed to evaluate the efficacy and safety of Tremfya in patients with moderate to severe active Crohn's disease (CD) who have had an inadequate response or intolerance to conventional therapies (immunomodulators, corticosteroids) and/or biologics (TNF antagonists, vedolizumab).

Image Source: 123RF

The results showed that both subcutaneous maintenance doses (200 mg every 4 weeks [q4w] and 100 mg every 8 weeks [q8w]) of Tremfya were superior to placebo.Stelara。Data show that both maintenance doses of Tremfya reached the co-primary endpoints compared to placebo.

At 48 weeks, both doses of Tremfya produced significantly better endoscopic outcomes compared to Stelara.The endoscopic response rates for the Tremfya high-dose and low-dose cohorts were 52.7% (p<0.001) and 47.9% (p=0.009), respectively, compared to 37.1% for the Stelara cohort.In terms of the endoscopic remission rate, 37.2% (p=0.001) of patients in the high-dose Tremfya cohort and 33.2% (p=0.024) in the low-dose cohort achieved this outcome, compared to only 24.7% in the Stelara group.

▲Summary of GALAXI Trial Results (Image Source: Reference [1])

In addition,In achieving deep remission (defined as achieving both clinical remission and endoscopic remission), the high-dose and low-dose Tremfya cohorts reached 33.8% (p=0.002) and 29.7% (p=0.040), respectively, compared to 22.3% in the Stelara group.

Tremfya has a good safety profile, and in the GALAXI program, its safety is consistent with the currently approved indications.

Tremfya is a specific anti-IL-23 monoclonal antibody that blocks the action of IL-23 by binding to its p19 subunit.In 2017, Tremfya was approved by the U.S. FDA for the treatment of adult patients with moderate to severe plaque psoriasis. In December 2019, Guselkumab (generic name: Guselkumab, trade name: Tremfya) was approved in China for adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. In 2020, it received U.S. FDA approval for the treatment of psoriatic arthritis.

Johnson & Johnson has submitted an application to the European Medicines Agency (EMA) this year, seeking approval to expand the indications of Tremfya to include adult patients with moderately to severely active ulcerative colitis (UC) and moderately to severely active Crohn's disease (CD). In addition, Johnson & Johnson has also submitted regulatory applications to seek approval for the use of Tremfya in treating adult patients with moderately to severely active UC in the United States and other countries or regions.

Many large pharmaceutical companies have clinical pipelines targeting Crohn's disease under their subsidiaries.In April this year,U.S. FDAApprovalEntyvio, developed by Takeda, targets α4β7 integrin.(Vedolizumab, an anti-integrin drug) Subcutaneous injection formulation for the maintenance treatment of adult patients with moderately to severely active Crohn's disease (CD) following induction therapy with the intravenous formulation of Entyvio.Eli Lilly and Company announced in October 2023 that its investigational monoclonal antibody mirikizumabPhase 3 Trial VIVID-1Achieved Co-Primary Endpoints in ChinaFor all primary and secondary endpoints, adult patients with moderate to severe active CD achieved significant clinical remission after receiving the treatment. Lilly intends to submit this positive Phase 3 trial data to the U.S. FDA and other global regulatory authorities as the basis for the therapy's marketing application for the treatment of Crohn's disease. In addition,Sanofi also partnered with Teva last year.Reach Cooperation, jointly develop its research therapy TEV’574.This is a TL1A antibody with a unique binding epitope. It blocks the binding of TL1A to the DR3 receptor without affecting TL1A's binding to the DcR3 decoy receptor. This selectivity may offer enhanced efficacy and safety. Currently, TEV’574 is in Phase 2b clinical trials for the treatment of ulcerative colitis and Crohn's disease.

References:

[1] TREMFYA® (guselkumab) demonstrates superiority versus STELARA® (ustekinumab) in Phase 3 Crohn’s disease program. Retrieved May 22, 2024 from https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-demonstrates-superiority-versus-stelara-ustekinumab-in-phase-3-crohns-disease-program

[2] J&J Positions Tremfya as Stelara Successor with Strong Head-to-Head Data. Retrieved May 22, 2024 from https://www.biospace.com/article/j-and-j-positions-tremfya-as-stelara-successor-with-strong-head-to-head-data/?utm_campaign=Newsletter%20%7C%20GenePool&utm_medium=email&_hsenc=p2ANqtz--JakClyQfJk7-aeyPnFBLWUyNXmsotuOI2uQUe96KTuHka4CN1JJBu0P8RqifmSUmIdT0dmGV91i_47GdcGwJ2lK37iBsO91THTPCnbzZfzhUxMz0&_hsmi=308244213&utm_content=308244213&utm_source=hs_email

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