Cristcot Announces FDA Acceptance of NDA for Next-Generation Hydrocortisone Acetate (ngHCA) for Treatment of Ulcerative Colitis (UC) of the Rectum

FDA Accepts Cristcot's NDA for ngHCA in Rectal Ulcerative Colitis

Cristcot announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for next-generation hydrocortisone acetate (ngHCA) 90-milligram suppository for the treatment of ulcerative colitis (UC) of the rectum. The FDA has set a Prescription Drug User Fee Act (PDUFA) target date of October 2026. This submission is supported by positive results from the pivotal Phase 3 CESSA trial, which met its primary endpoint of clinical remission based on the Modified Mayo Score of 0-2 at Day 29. If approved, ngHCA would be the first and only FDA-approved hydrocortisone acetate suppository, with commercial launch readiness planning underway for the fourth quarter of 2026.

• The FDA's acceptance of Cristcot's 505(b)(2) NDA for ngHCA marks a critical regulatory milestone, setting a PDUFA target date for October 2026. This positions ngHCA to potentially become the first FDA-approved hydrocortisone acetate suppository, addressing a significant unmet need for patients with ulcerative colitis of the rectum.
• The NDA is underpinned by robust data from the Phase 3 CESSA trial, which demonstrated statistically significant rates of clinical remission. The trial successfully achieved its primary endpoint, defined as a Modified Mayo Score of 0-2 at Day 29, highlighting ngHCA's efficacy in treating the localized inflammation characteristic of rectal UC.
• ngHCA is an investigational 90 mg hydrocortisone acetate suppository delivered via Cristcot’s patented Sephure® applicator, designed for rapid, sustained release with limited systemic exposure. This novel approach aims to overcome treatment barriers, enhance patient compliance, and provide a targeted therapeutic option for the approximately 1.3 million UC patients in the U.S., particularly those with rectal disease involvement.

The Unmet Need in Rectal Ulcerative Colitis Treatment

Current treatment approaches for ulcerative colitis of the rectum face significant challenges despite recent therapeutic advances. Existing therapies remain insufficient to fully reverse mucosal injury or restore normal physiological homeostasis, with many patients experiencing treatment failure, relapse, or adverse effects. These limitations persist even as biologics and novel small molecules have expanded the therapeutic landscape.

• Incomplete therapeutic response - Many patients with moderate-to-severe disease continue to experience treatment failure and relapse despite the advancement of biologics in UC management, with current therapies unable to fully reverse mucosal injury or restore normal physiological homeostasis

• Significant adverse effect profiles - Current treatments are limited by strong drug resistance and substantial adverse effects, with specific concerns including tofacitinib's association with higher risks of herpes zoster and thromboembolic events

• Targeted drug delivery challenges - Conventional drug delivery systems encounter numerous obstacles reaching the colon, including physiological barriers, disease severity variations, genetic variants, and nutritional status factors that result in nonspecific tissue distribution and uncontrolled drug release

• High hospitalization and surgical rates - Approximately one-fifth of patients require hospitalization, and 20-30% of those experiencing acute flares will undergo colectomy, indicating inadequate disease control with current medical management

• Cost and accessibility barriers - High drug prices and various adverse effects limit the clinical application of newer therapies, particularly affecting treatment accessibility in different healthcare systems

• Limited treatment targeting - Existing pharmacological interventions primarily rely on broad anti-inflammatory approaches through corticosteroids, aminosalicylates, biologics, and immunomodulators rather than treatments specifically designed to act directly on colonic tissue

Understanding the Patient Burden of Rectal Ulcerative Colitis

Ulcerative colitis demonstrates significant geographic and ethnic variation in its epidemiologic patterns. The disease incidence ranges from 3 to 15 cases per 100,000 persons annually with a prevalence of 50-80 cases per 100,000. Jewish populations show particularly high susceptibility, with rates 3-5 times higher than general populations. Within Jewish communities, Ashkenazi Jews exhibit higher incidence than Sephardi Jews in Israel, though still lower than Ashkenazi populations in the United States or Northern Europe. Notably, previously documented racial and ethnic differences appear to be narrowing over time, and urban populations demonstrate higher incidence rates compared to rural areas.

Age distribution varies significantly across different geographic populations and appears to be shifting over time. In Israeli kibbutz populations, the mean age at presentation increased from 46.14 years in 1987 to 51.43 years in 1997, suggesting a trend toward later onset. However, substantial regional variation exists, with Arab populations in Kuwait showing a median diagnosis age of 28.5 years and Chinese populations averaging 40.6 years at diagnosis. Pediatric ulcerative colitis represents a growing concern, with prevalence in children under 17 years increasing dramatically from 0.7 per 100,000 in 1978 to 12.7 per 100,000 in 2007 in Manitoba, Canada.

Gender distribution patterns show mixed findings across populations, with overall rates appearing relatively balanced but varying by geographic region. Recent data from Brazil demonstrates female predominance with a 1.48:1 female-to-male ratio, while historical German data showed male predominance. Israeli kibbutz studies found slightly higher prevalence in women (female:male ratio 1.19), and contemporary research indicates that women with inflammatory bowel disease tend to report lower quality of life, utilize healthcare resources at higher rates, and experience different treatment patterns, including lower rates of colectomy compared to men.

CESSA Phase 3: Clinical Evidence for ngHCA in Rectal UC

Recent clinical trials in ulcerative colitis have employed diverse study designs and endpoints, though standardization remains challenging. Multiple phase 3 trials have demonstrated varying approaches to evaluating therapeutic efficacy, with most incorporating both clinical and endoscopic assessments as primary endpoints.