Cristcot, a clinical-stage pharmaceutical company, announced pivotal Phase 3 trial results for its novel hydrocortisone acetate suppository in ulcerative colitis (UC) treatment, demonstrating statistically significant clinical remission rates that represent a breakthrough in rapid-acting UC therapy. The company will present three posters highlighting these findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting in Phoenix, Arizona.
Phase 3 CESSA Trial Achieves Primary Endpoints
The Phase 3 CESSA trial evaluated Cristcot's next-generation hydrocortisone acetate (ngHCA) 90 mg suppository administered with the proprietary Sephure® suppository applicator in adults with confirmed active moderate to severe UC. The trial achieved both its primary endpoint of clinical remission at Day 29 and secondary endpoint of clinical response at Day 15, using modified Mayo Score (MMS) criteria.
Clinical and endoscopic remission was achieved by 21.2% of study participants in the ngHCA once-daily arm versus 1.5% of patients in the placebo arm (p=0.0005). Secondary efficacy analyses showed that treatment with ngHCA once-daily resulted in greater improvement in rectal bleeding and stool frequency scores at Day 15 and Day 29 versus placebo.
"The efficacy demonstrated in CESSA, notably clinical responses within two weeks and endoscopic remission by four weeks, has never been achieved in the moderate to severe UC population," said Raj Devarajan, MD, Global Medical Advisor at Cristcot and presenting author.
Safety Profile and Patient Compliance
The investigational therapy demonstrated an excellent safety profile throughout the trial. There were no treatment-related serious adverse events (SAEs), and treatment-related adverse events (TEAEs) were reported by 4.5% of patients in the once-daily treatment group compared to 7.6% in the placebo group. The majority of TEAEs were mild and moderate in severity.
Patient compliance was exceptional, with 100% of subjects in the ngHCA once-daily group achieving greater than 90% adherence with the required dosing. Concomitant medication for UC at stable doses was taken by 63.5% of patients throughout the study, while no non-study corticosteroids were permitted.
Presidential Poster Recognition
The CESSA abstract was selected as an ACG 2025 Presidential Poster Recipient among nearly 6,000 abstracts. This distinction is reserved for approximately five percent of submissions and recognizes high-quality, novel, and clinically meaningful research contributing to advances in gastroenterology.
"We are excited to present Cristcot's data at ACG 2025, which showcases our meaningful contributions across the spectrum of UC research and reinforces the transformative potential of our ngHCA suppository - the first investigational agent to show rapid clinical remission in UC," said Jennifer J. Davagian, Founder and Chief Executive Officer of Cristcot.
Innovative Drug Delivery Technology
Cristcot's investigational hydrocortisone acetate 90 mg suppository formulation represents a novel corticosteroid therapy delivering a small volume suppository using the Sephure® applicator to ensure precise placement, minimizing discomfort and leakage. Unlike traditional corticosteroid treatments, the advanced HCA formulation allows for rapid, sustained release with optimal bioavailability, consistent and localized efficacy, and very limited systemic exposure.
A Phase 1 study demonstrated that the ngHCA suppository administered using the Sephure® suppository applicator showed sustained release with optimal bioavailability expected to provide consistent efficacy over the intended treatment period.
Addressing Unmet Medical Need
UC is a life-long, chronic gastrointestinal autoimmune disease characterized by inflammation and ulcers in the lining of the large intestine. Over 55% of UC patients experience 3-5 flares annually, with many reporting debilitating effects on daily activities, work, and mental health. Despite existing treatments, patients experience intermittent flares and often change therapies as a measure to treat increased disease activity.
"There is an urgent need for a fast-acting, localized, and easy-to-administer option to manage patients with active ulcerative colitis," said Dr. Devarajan. "Combined with a favorable tolerability profile, these data support this novel HCA combination product to treat UC exacerbations alongside maintenance therapies or as a monotherapy."
The company is progressing towards FDA submission and commercialization of the novel therapy, with additional research including an exploratory analysis demonstrating that recent recall offers a reliable, lower-burden alternative to daily diaries for collecting patient-reported outcomes in future UC trials.
