Evaluating inflammatory bowel disease therapies require active comparators

At Digestive Disease Week (DDW) 2023, a comment was made following a presentation discussing the preliminary induction findings from the Phase IIb/III QUASAR (NCT04033445) trial in ulcerative colitis (UC). A member of the audience questioned the overall conclusion that guselkumab (GUS) is a “great therapy”. The attendant pointed out that GUS was shown to only affect remission in less than a quarter of the treated patients (22.5%), with a moderate benefit over placebo of only approximately 12%. The individual continued to argue that GUS and many other inflammatory bowel disease (IBD) therapies do not meet the historical therapeutic standards, referencing a recent meta-analysis study that showed that treatments generally achieve a 20% delta over placebo. At the crux of this line of thought is a lack of evidence to support the market narrative and messaging of “high quality” current and upcoming IBD therapies, and a need for better data.

Observed from recent interviews of key opinion leaders (KOLs) within IBD conducted by GlobalData, the unmet need for more evidence to define the most efficacious therapy has been echoed repeatedly. One such thought leader acknowledged the current status quo with companies being able to “get away, so to speak, in the IBD field with these placebo-controlled trials”, adding that the sole use of placebo is not the norm with other indications. “I think you see more comparative effectiveness trials in some of the other fields, certainly in oncology… it’s always the standard of care versus the new thing.” Addressing this situation not only improves the quality of care for the IBD patient population, but it would benefit companies in a quickly evolving and expanding market.

Addressing this unmet need is increasingly important following recent bets within IBD and immunology through mergers and acquisitions such as the purchase of Prometheus Biosciences by Merck for $10.8bn, or the $2.4bn offer by Lilly for Dice Therapeutics. In addition to the effect, these strategic transactions will have on the market in the coming years, long-established agents such as Humira and Stelara are transitioning to legacy assets, providing the opportunity for the next generation of treatments to capture significant market share. The current situation would be best addressed through clinical asset evaluation through trials with active comparators, but of the eight late-stage pipeline agents at the beginning of this year, only Janssen’s mirikizumab and Pfizer’s brazikumab were being evaluated against active comparators (ustekinumab and adalimumab respectively), with the former programme ending following assessment of the competitive landscape. The higher probability of trial failure when incorporating active comparators during therapy development is known, but investigators should not overlook the benefit of establishing confidence with decision-makers.