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WASHINGTON -- Induction and maintenance treatment with guselkumab (Tremfya) demonstrated its safety and efficacy for patients with moderately to severely active Crohn's disease, topping both placebo and an active comparator in a pair of phase III trials.

The identically designed GALAXI 2 and GALAXI 3 trials met both of their composite co-primary endpoints, demonstrating significantly improved rates of response and remission with two different dosing regimens of the dual-acting interleukin (IL)-23 inhibitor versus placebo (P<0.001 for all comparisons):

• Clinical response at week 12 plus clinical remission at week 48: 47-55% with guselkumab vs 12-13% with placebo
• Clinical response at week 12 plus endoscopic response at week 48: 34-39% vs 5-6%, respectively

"The two double-blinded GALAXI phase III studies independently established the short-term and long-term efficacy of the dual-acting IL-23 inhibitor guselkumab compared to placebo in participants with moderately to severely active Crohn's disease," said Remo Panaccione, MD, of the University of Calgary in Alberta, in a late-breaking presentation at the annual Digestive Disease Week (DDW) conference.

Furthermore, "guselkumab demonstrated statistical superiority to ustekinumab [Stelara] in prespecified and multiplicity controlled analyses of pooled data at week 48," he said.

That secondary outcome showed significant improvements with the two guselkumab dosing regimens tested versus ustekinumab for week-48 rates of endoscopic response (48-53% vs 37%, respectively), endoscopic remission (33-37% vs 25%), clinical plus endoscopic remission (42-47% vs 34%), and deep remission (30-34% vs 22%).

Johnson & Johnson is developing guselkumab to replace its IL-12/23 blocker ustekinumab, which approaches a patent cliff as biosimilars head to the market. Guselkumab is also being developed in ulcerative colitis, but is currently only approved for plaque psoriasis and active psoriatic arthritis.

The "buzz about guselkumab is pretty hot, probably about the level of ustekinumab when that first came out for treatment of inflammatory bowel disease," DDW session moderator Phillip Ge, MD, of MD Anderson Cancer Center in Houston, told 名媛直播. "Where guselkumab will fit in the treatment algorithms may depend on a number of items, not the least of which will be insurance reimbursement. But it will fit in somewhere in clinical practice."

However, "if I had a patient that was doing well on ustekinumab, I probably wouldn't switch them based on the data presented," Ge said. "But if they weren't doing well, switching to guselkumab is something I would think about."

Panaccione presented data on the primary analysis of , which included a total of 1,021 patients with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score of 220-450 plus either a mean daily Stool Frequency count >3 or an Abdominal Pain score >1). Participants also needed to have inadequate response/intolerance to conventional therapies, such as immunomodulators or corticosteroids, and/or biologics.

Across study arms, participants had a mean age of 36.5 years, 58% were men, and the mean duration of their disease was over 7 years. Mean CDAI score at baseline was 294.8 while a little over a quarter of patients had severely active Crohn's disease on endoscopic disease activity scores. Overall, 42% of the trial populations were biologic naive and 52% had a history of intolerance or inadequate response to biologic therapy (including at least one TNF inhibitor in 96%).

Patients were randomized in a 2:2:2:1 ratio to the following four treatment arms: guselkumab IV induction (200 mg) followed by 200 mg subcutaneous maintenance starting at week 12; guselkumab induction followed by 100 mg subcutaneous maintenance starting at week 16; ustekinumab IV induction (6 mg/kg) followed by 90 mg subcutaneous maintenance dosing starting at week 8; or placebo induction and maintenance (with non-responders crossing over to ustekinumab).

Responses to induction with guselkumab at week 12 occurred in 61-64% of patients in the two trials versus 18-29% of placebo patients. Clinical remission at week 12 occurred in 47% of guselkumab-treated patients versus 15-22% of placebo patients, while endoscopic response at that timepoint occurred in 36-38% and 11-14%, respectively.

Guselkumab's safety profile was consistent with previous trials of other conditions the drug is for, said Panaccione.

Through week 48, the number of patients with at least one adverse event (AE) occurred in 76-78% of the guselkumab-treated patients, 79% of the ustekinumab group, and 54% of the placebo group. Serious AE rates were similar across study arms (7-12%), as were treatment discontinuation rates (6-9%). The proportions of patients with serious infections or AEs of interest were low, said Panaccione, and no deaths occurred in any of the trial arms.

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