Brian Feagan, MD, on the VEGA Study of Combined Biologics in Ulcerative Colitis

Dr Feagan reviews the findings of the VEGA study, which examined the efficacy of combining guselkumab, an interleukin-23 inhibitor, with golimumab, a tumor necrosis factor inhibitor, compared to using just a single agent in treating patients with ulcerative colitis.

Brian Feagan, MD, is professor of medicine at the Schulich School of Medicine & Dentistry of Western University in London, Ontario, Canada, and senior scientific director of Alimentiv Inc.

TRANSCRIPT:

Hello, I'm Dr. Brian Feagan, professor of medicine at Western University in Ontario, Canada. I'm very pleased to report the results of the VEGA study, which has recently been completed. And this is the first large-scale evaluation of combined monoclonal antibody therapy for the treatment of ulcerative colitis.

As a way of introduction, you all know that we have many new treatments for ulcerative colitis that have been introduced over the past 20 years, and these include TNF antagonists, vedolizumab, the anti-12/23 antagonists, JAK inhibitors, and S1P1 modulators. Now, despite the influx of new tools in the toolbox, remission rates with these therapies remain relatively low in relationship to other chronic inflammatory diseases where, for example, the interleukin 23 antagonists have revolutionized the treatment of psoriasis, attaining 80 to 90% remission rates. So we've got a long way to go in ulcerative colitis therapy.

Now, approaches to this problem would include combining drugs, or, alternatively, personalized medicine approaches. And VEGA is really based on the former approach, taking 2 agents that have been shown to be effective in inflammatory bowel disease, that's a TNF antagonist, golimumab, and the anti-IL-23 antagonist, guselkumab, and combining them in a randomized controlled trial comparison.

So VEGA has evaluated approximately 210 patients, randomized 70 per group to the combination of the 2 monoclonal antibodies, or the individual components as monotherapy. The primary analysis of the study was based on 12 weeks of therapy and clinical response, defined by a 30% reduction in the total Mayo Score, was the primary endpoint; prespecified secondary endpoints with clinical remission using the conventional regulatory definition, essentially a Mayo Endoscopic Clinic Score of 0 or 1, having entered the trial with a 2 or 3, and cessation of bleeding.

The results of the study were, I think, quite convincing, showing adaptivity of the combination therapy over the individual monotherapies. At week 12, there was a very high remission rate in the combination therapy group exceeding 80%, and that was statistically significant over the golimumab monotherapy arm. The trend was in the right direction for the guselkumab comparison, but it was not statistically significant. In contrast, with regard to the remission endpoint, as I mentioned, the regulatory endpoint, and arguably more clinically meaningful endpoint, there was a superiority of combo to both of the monotherapies at 12 weeks.

This trial also featured a continuation up to 50 weeks of therapy, and after 12 weeks, the combination therapy group, the TNF antagonist was dropped, and these patients received guselkumab monotherapy. And at the end of 50 weeks, the point estimates still favored the combination therapy, despite the cessation of the combo at week 12.

We were very interested in side effects in this trial, because the potential theoretical consideration of increased risk of infection. And I'm pleased to report that there was not a strong signal for any new toxicity beyond observed with the individual agents, or an increased risk of infection with the combined therapy.

So, in summary, this was a very successful demonstration project that showed a way forward with combined therapy. And I think you're going to see more of these types of studies. In fact, there's an extensive phase 2 program exploring this combination, and we should have results from that program within the next year or so. So thank you for your attention.