Breakthrough Clinical Results

Abivax announced positive topline results from its Phase 3 ABTECT-1 and ABTECT-2 trials evaluating obefazimod, a first-in-class oral miR-124 enhancer, in adult patients with moderately to severely active ulcerative colitis (UC). The 50mg once-daily dose achieved the primary endpoint of clinical remission at Week 8 in both trials, demonstrating a pooled placebo-adjusted remission rate of 16.4%. The drug also met all key secondary endpoints. Obefazimod showed a favorable safety profile. A maintenance trial is ongoing, with results expected in Q2 2026, after which Abivax plans to submit a New Drug Application to the FDA.

Study Design Parameters

Study Design Parameters and Endpoints in Key Ulcerative Colitis Trials

Study Designs

• Scientific literature reviews using MEDLINE focused on biologic medical therapies
• Randomized controlled trials with parallel arm or cross-over designs
• Observational real-world evidence (RWE) studies like the VEDO registry which enrolled 512 patients across 45 IBD centres in Germany
• Retrospective analyses of medical records and claims data
• Cross-sectional studies including online surveys with 775 adult UC patients
• Propensity score adjustment with inverse probability of treatment weighting used to correct for confounding

Primary Endpoints

• Clinical remission measured using partial Mayo (pMayo) score
• Combined clinical and endoscopic remission at week eight in budesonide-MMX® trials
• Modified ITT analysis where switching to a different biologic agent was considered failure
• Steroid-free remission as an important endpoint in biologic therapy studies
• Clinical response defined by reduction in disease activity indices

Secondary Endpoints

• Disease activity assessed using:

• CRP (C-reactive protein)

• ESR (erythrocyte sedimentation rate)

• Endoscopic improvement

• Histologic improvement

• Safety endpoints including:

• Adverse events (AEs) and serious AEs

• Opportunistic infections

• Malignancies

• Major adverse cardiovascular events (MACE)

• Gastrointestinal perforations

• Patient-reported outcomes (PROs)
• Biomarker measurements with biosamples collected from patients
• Steroid-sparing effect
• Study withdrawals

Results from Key Trials

• Induction therapy showed similar clinical remission rates between vedolizumab and anti-TNF agents (23% vs. 30.4%)
• Two-year clinical remission rates were significantly higher for vedolizumab than anti-TNF agents (43.2% vs. 25.8%)
• Treatment switching was lower with vedolizumab (29%) compared to anti-TNF agents (54%)
• Infliximab demonstrated efficacy for inducing remission in moderate-to-severe UC
• Vedolizumab and other anti-integrin antibodies showed efficacy with favorable safety profiles
• JAK inhibitors like tofacitinib and upadacitinib were evaluated for efficacy and safety
• Budesonide was compared to mesalamine, placebo, and prednisolone in different studies

Study Populations

• Trials included patients with active, moderate-to-severe ulcerative colitis
• Some studies specifically targeted steroid-dependent and steroid-resistant UC patients
• Patient populations ranged from adults to pediatric patients (112 children in one study)
• Studies included both biologic-naïve and biologic-experienced patients

Incidence and Prevalence

Latest Estimates of Ulcerative Colitis Incidence and Prevalence Globally

The available data on global incidence and prevalence of Ulcerative colitis (UC) shows significant geographical and ethnic variations. While comprehensive global estimates are limited in the provided information, several important regional patterns can be identified.

Regional Variations

A 2015 study from Canada revealed that immigrants had a significantly lower incidence of inflammatory bowel disease (IBD) at 7.3 per 100,000 person-years compared to 23.9 per 100,000 in non-immigrants (incidence rate ratio (IRR) 0.34, 95% CI 0.26-0.44). Among immigrant populations, those from East Asia showed the lowest incidence (IRR 0.14, 95% CI 0.11-0.18), while immigrants from Western Europe/North America had the highest rates (IRR 0.59, 95% CI 0.46-0.75).

Age-Related Factors

Age at immigration appears to be a significant factor, with increased age being associated with decreased risk of IBD (HR 0.986, 95% CI 0.982-0.990). This represents a 14% increased risk per younger decade of life at immigration, suggesting environmental factors during early life may play a crucial role in disease development.

Ethnic Differences

A 2015 study examining Uyghur and Han populations in China found differences in genetic susceptibility to ulcerative colitis between these ethnic groups. Among Uyghur populations, the HLA-DRB1*08 gene frequency was lower in UC patients than in controls, while HLA-DRB1*13 was much higher in UC patients. In contrast, Han patients with UC showed no significant difference in HLA-DRB1 frequency compared to healthy controls.

Additionally, the positive rate of ANCA (antineutrophil cytoplasmic antibodies) in Uyghur patients with UC was significantly higher than in Han UC patients, further highlighting ethnic differences in disease manifestation.

European Data

A 1999 study from Barcelona, Spain reported a mean annual incidence of 1.1 per 100,000 inhabitants (95% CI, 0.4-1.7) for collagenous colitis and 3.1 per 100,000 inhabitants (95% CI, 2.0-4.2) for lymphocytic colitis.

Research Gaps

It's worth noting that a 2020 source identified "understanding the incidence and prevalence of IBD" as one of the gaps that need to be addressed, proposing "epidemiological studies in ethnically and geographically diverse cohorts to estimate incidence and prevalence of IBD."

The variation in incidence rates across different populations highlights the complex interplay between genetic susceptibility and environmental factors in the development of ulcerative colitis, emphasizing the need for more comprehensive global epidemiological studies.

HTA Approvals

Drug used in other indications

Obefazimod Clinical Trials Beyond Ulcerative Colitis

Based on a thorough review of the available information, I cannot provide details about Obefazimod (also known as ABX464) clinical trials for indications other than ulcerative colitis. The information about this investigational drug's clinical development program, including its intervention models, randomization protocols, control methodologies, and trial designs for various indications is not available in the reference material.

Similarly, information regarding the primary and secondary endpoints in clinical trials investigating Obefazimod for non-ulcerative colitis indications cannot be determined from the available data.

For comprehensive and accurate information about Obefazimod's clinical trial program, it would be advisable to consult:

• Clinical trial registries such as ClinicalTrials.gov
• The pharmaceutical company developing the drug
• Published medical literature in peer-reviewed journals
• Regulatory authority websites such as the FDA or EMA

These sources would provide reliable information about the current status of Obefazimod's development across various therapeutic areas and the specific intervention models being employed in these clinical investigations.