At Digestive Disease Week (DDW) 2023, a comment was made following a presentation discussing the preliminary induction findings from QUASAR (NCT04033445), the Phase IIb/III trial evaluating Janssen’s guselkumab (GUS) in ulcerative colitis (UC). A member of the audience questioned the talk’s overall conclusion that GUS is a “great therapy”. This individual’s comment reflects an overarching belief within the field that treatments for inflammatory bowel disease are entering an inflection point requiring active comparators, according to GlobalData, a leading data and analytics company.

The attendant continued by pointing out that GUS was shown to only effect remission in less than a quarter of the treated patients (22.5%), with a moderate benefit over placebo of only approximately 12%. The commenter concluded the argument with the observation 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.

Adeleke Badejo, Senior Analyst – Immunology at GlobalData, comments: “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 in the field 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 also would benefit companies in a quickly evolving and expanding market.

Badejo continues: “The significance of addressing this unmet need is of increased importance in light of recent bets within IBD and immunology through mergers and acquisitions, such as the purchase of Prometheus Biosciences by Merck for $10.8 billion, or the $2.4 billion 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 Lilly’s mirikizumab and AstraZeneca’s brazikumab were being evaluated against active comparators (ustekinumab and adalimumab respectively), with the former program ending following assessment of the competitive landscape.

Badejo concludes: “The apparent risk with higher probability of failure associated with incorporating active comparators during therapy development is known, but the benefit in establishing confidence with decision makers should not be overlooked.”