Dr Panaccione reviews the results of the GALAXI 2 and 3 trials of guselkumab for treatment of Crohn's disease, which he presented at Digestive Disease Week 2024.

Remo Panaccione, MD, is a professor of medicine and the director of the Inflammatory Bowel Disease Unit and of the IBD Fellowship Program at the University of Calgary, Calgary, Canada. 

Hello everyone, I'm Remo Panaccione, Professor of Medicine and Director of the IBD Clinic at the University of Calgary in Calgary, Canada. I'm here at DDW in Washington, DC, where I've just finished presenting the pivotal phase 3 results of the GALAXI 2 and 3 trials in moderate to severe Crohn's disease. So just to give you an overview of what that trial was, these were 2 large phase 3 trials in patients with moderate to severe Crohn's disease. They were randomized, double blind, double dummy, treat-through trial designs, evaluating the efficacy of guselkumab, which is an anti-p19 inhibitor that works by neutralizing not only IL-23, but by binding CD64, which is a receptor on cells that produce IL-23.

So what did we do in these 2 studies that involved over 1000 patients, approximately 500 each? We tested the efficacy and safety of guselkumab at an IV followed by 2 subcutaneous dosing regimens versus placebo, but also to an active comparator ustekinumab, which is part of the standard of care of moderate to severe Crohn's disease. So that comparator is extremely important as we bring new therapies to the market.

This involved very robust endpoints, what we call coprimary composite endpoints at the individual patient level, so to be a success in this trial, you needed to meet not only the clinical endpoints early on of clinical response, but then later endpoints as well, which were clinical and endoscopic endpoints. And we really know that those endoscopic endpoints are very, very important because, A, there's a discrepancy sometimes between symptoms and the endoscopic findings, but more importantly, if we can meet those endoscopic endpoints, we know that that pays you forward with decreased flares, hospitalization, and surgery. So those endpoints are really, really important for us to focus on.

So what did we show? So for the comparisons for placebo against guselkumab, the IV doses and the sub-q doses were superior to placebo across a variety of endpoints both early on, after week 12, both the clinical and the endoscopic endpoints, and out to week 48, so meeting those composite endpoints at week 12 and 48. And what was very nice to see because these were two separate trials is that there was consistency across both GALAXI 2 and GALAXI 3 where we analyze the data separately. When we then looked at something that I think our field is really interested in, which is that comparison against ustekinumab, this was done as a pooled analysis of the GALAXI 2 and GALAXI 3 studies, and it was done at week 48 in this treat-through design.

And what did we see there? We saw that both doses of the subcutaneous guselkumab were statistically superior to ustekinumab for most importantly for the endoscopic endpoints of endoscopic response, a very tough endpoint of endoscopic remission, the composite endpoint of a clinical response and endoscopic response, and a very, very high bar, which we call deep remission, which is the combination of clinical remission, the patient's feeling normal and endoscopic remission, which had a definition according to one of our metrics. So very positive results that now we have a new entry into our therapeutic armamentarium because of these endoscopic results, especially the comparison against something that's already in the market.

Puzzlingly, when we look at clinical remission, the clinical remission rates were very high, almost touching 70% at the end of 48 weeks for the 2 different doses. But the clinical remission rate for ustekinumab was also high, so it didn't reach statistical significance for that. But I think that that highlights the fact that, you know, subjective endpoints, such as clinical remission, may not really give us the full flavor and efficacy of a therapy. And finally, the drugs were well tolerated at both doses, and there were no new safety signals.

And, you know, when we look at these results— also at this meeting, there were the results of the phase 3 trial in moderate to severe ulcerative colitis that was presented by my colleague, David Rubin. And those were positive results as well. So what we're building on is a story of what guselkumab will mean to moderate to severe IBD, both ulcerative colitis and Crohn's disease.

And this story is going to continue to evolve because there's an ongoing program evaluating sub-q induction with guselkumab and sub-q maintenance therapy, which I think will be very well received by our GI community. So thank you for taking the time to listen. I hope this was valuable for you.