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ORAL MUFEMILAST (A NOVEL SELECTIVE PDE4INHIBITOR) DEMONSTRATES EFFICACY AND SAFETY IN A PHASE II MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED INDUCTION TRIAL IN CHINESE PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS

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Introduction

Despite recent advances in IBD therapy, there is a need for novel effective, safe oral drugs. Mufemilast has demonstrated sustained efficacy and safety in plaque psoriasis¹. Here we report the efficacy and safety of Mufemilast at 12 weeks from this phase 2 trial (NCT05486104).

Aims & Methods

Patients with moderate to severe UC were randomized (1:1:1) to placebo (n=31), mufemilast 45mg (n=31) or 60mg (n=30) twice daily (BD) for 12 weeks. Eligibility criteria required participants to have a modified Mayo score (mMS) of 4-9, including an endoscopy score of ≥ 2 , inadequate /loss of response to conventional therapy (5-ASA, Steroids, immunomodulators), or biologics (anti-TNF, anti-integrin, anti-interleukin 12/23). Stable co-treatment with oral 5'ASAs and corticosteroids was permitted if it was stable for at least ≥2 weeks before microscopy within the screening period and needed to remain stable for the duration of the study. Patients with positive Quantiferon tests were also eligible. Efficacy definitions were according to FDA guidance².

Results

Ninety-two patients with moderate to severe UC were randomized (1:1:1) placebo (n=31), mufemilast 45mg (n=31) or 60mg (n=30) twice daily (BD) for 12 weeks. Efficacy parameters were defined; clinical remission as a stool frequency subscore of 0 or 1 and no greater than baseline, a score of 0 for rectal bleeding subscore, and a subscore of 0 or 1 for endoscopy (without friability); clinical response as a ≥2-point reduction in mMs from baseline and a ≥30% decrease from baseline, with a ≥1-point reduction in rectal bleeding subscore from baseline, or a ≤1-point rectal bleeding subscore; mucosal healing a mMS endoscopic subscore of ≤1 point². A Chi-square test was used to compare the differences between groups. Safety evaluated the number and severity of AEs, including vital signs, safety laboratory values, and ECGs. There was 1 SAE (possibly related; thrombophlebitis, a preexisting condition) and 2 AEs that led to discontinuation in the 60 mg group (1 pain in the extremities,1 headache). Most AEs were mild or moderate, and the number of subjects reporting AEs was evenly distributed across the placebo and mufemilast groups. There were no clinically relevant changes in vital signs, laboratory values, or ECG parameters, which raised any concerns. Table 1 summarises the efficacy data. A subgroup analysis confirmed similar efficacy and safety in Quantiferon-positive and negative patients and between Biologic-naive and Biologic-exposed patients.

Table 1 (²FDA Criteria; FAS)12 week data	Placebo (n)	45mg (n)	60mg (n)
Population
5'ASA Concomitant treatment	81%	87%	90%
Moderate (4≤mMS ≤ 6)	45%	52%	50%
Severe (7≤mMS ≤ 9)	55%	48%	50%
Efficacy
²Clinical Remission^*	13% (4/31)	39% (12/31)	57% (17/30)
²Clinical Response^**	42% (13/31)	87 % (27/31)	80 % (24/30)
²Mucosal Healing	16 % (5/31)	42% (13/31)	67% (20/30)
^delta vs placebo for clinical remission 44% for 60mg (p<0.001) and ^* 26% for the 45mg group (p<0.07)

Conclusion

Mufemilast efficacy and safety were consistent across subgroups regardless of previous biologic use, suggesting Mufemilast is a viable potential future treatment option in patients with moderate to severe UC that breaks through the current 20% ceiling for clinical remission. A phase 3 study will be conducted to confirm these results.

References

¹Jones, C.; Zhang, J.; Wang, L.; Dai, X.; Wang, H.; Bi, X.; Duan, X.; Meng, Z.; Tian, Z.; Xu, A.; et al. A Double-Blind, Placebo-Parallel Controlled Phase III Clinical Study of the Efficacy and Safety of Hemay005 Tablets in Patients with Moderate to Severe Chronic Plaque Psoriasis in China. Arthritis Rheumatol ACR Converg. 2023, 75.
²Food and Drug Administration. Ulcerative Colitis: Developing Drugs for Treatment. Guidance for Industry - Draft Guidance; 2022. Accessed May 11, 2025. https://www.fda.gov/media/158016/download

ORAL MUFEMILAST (A NOVEL SELECTIVE PDE4INHIBITOR) DEMONSTRATES EFFICACY AND SAFETY IN A PHASE II MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED INDUCTION TRIAL IN CHINESE PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS

Charles Jones 1, Shutian Zhang 2, Changqing Zheng 3, Bing Rong Liu 4, Xiuli Zuo 5, Shigang Ding 6, Xiaoyun Ding 7, Liangping Li 8, Youxiang Chen 9, Xu Ren 10, Chengxia Liu 11, Xiaowei Liu 12, Chengdang Wang 13, Hong Guo 14, Ruimiao Yu 15, baohong xu baohong xu 16, Feng TIAN 3, Xiaohua Hou 17, Hui Yang 18, Zhaohui Yu 19, Xiangpeng Hu 20, Yue Zhen 1, Zhihong Wang 1, Han Hai 1, Aihong Huo 1, Hesheng Zhang 1

1 Tianjin Hemay Pharmaceuticals, Tianjin, China

2 Beijing Friendship Hospital, Beijing, China

3 Shengjing Hospital of China Medical University, Shenyang, China

4 The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

5 Qilu Hospital of Shandong University, Jinan, China

6 Peking University Third Hospital, Beijing, China

7 The First Affiliated Hospital of Ningbo University, Ningbo, China

8 Sichuan Provincial People's Hospital, Chengdu, China

9 The 1st Affiliated Hospital of, Nanchang, China

10 Heilongjiang Provincial Hospital, Harbin, China

11 Affiliated Hospital of Binzhou Medical College, Binzhou, China

12 Xiangya Hospital, Changsha, China

13 The First Affiliated Hospital of Fujian Medical University, Fuzhou, China

14 Chongqing People's Hospital, Chongqing, China

15 Chifeng City Hospital, Chifeng, China

16 Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China

17 Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

18 The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

19 The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

20 The Second Affiliated Hospital of Anhui Medical University, Hefei, China

Event

UEG Week Berlin 2025

Topics

Endoscopy IBD Mechanisms & Personalised Medicine

Submission format

Late-Breaking Abstract

Session

Hot off the press: IBD treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Presidential address

Matthias Löhr 1

1 Karolinska Institutet, Stockholm, Sweden

Event

UEG Week Berlin 2025

Topics

Immunology

Session

Opening Plenary

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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FERMENTABLE FIBER INTAKE AND REDUCED CROHN’S DISEASE RISK: INSIGHTS FROM THE GEM PROSPECTIVE COHORT

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Introduction

The cause of Crohn’s Disease (CD) remains unclear; however evidence suggests that dietary factors play a key role. With a rising incidence and no definitive cure, identifying modifiable risk factors is critical in preventing CD development. We aimed to study the association between fermentable dietary fibre intake and the future development of CD in an at-risk population.

Aims & Methods

Participants were recruited as part of the Crohn’s and Colitis Canada GEM study, a prospective cohort study of healthy first-degree relatives of patients with CD. At enrolment, a validated food frequency questionnaire was administered. Pectin, β-glucan, inulin, fructooligosaccharides (FOS), and arabinoxylan intake were quantified, and values energy-adjusted. Survival analysis was used to test the association between intake of fibre subtypes and risk of CD development. Generalized estimating equation tested the association between fibre intake and baseline impaired intestinal permeability (fractional urinary excretion of lactulose to mannitol ratio (LMR) >0.025); subclinical gut inflammation (faecal calprotectin (FCP) >250 μg/g); and faecal microbiome composition via 16s rRNA sequencing.

Results

76 of the 2,659 participants developed CD with a median follow-up of 8.9 years (IQR=5.7-12.3). Median age at recruitment was 17 years (IQR=12-25). 47% were male. Higher intake of inulin (HR = 0.78; 95% CI=0.61–0.99; p=0.04) and β-glucan (HR = 0.78; 95% CI=0.61–0.99; p=0.04) were associated with a reduced risk of CD development. No fibre subtype was associated with a higher risk of CD development. Lower intake of pectin, inulin, FOS and β-glucan was associated with impaired intestinal permeability (0.005<p<0.04). Lower inulin intake was associated with high FCP levels (p = 0.046). Higher pectin intake was associated with increased alpha diversity of faecal microbiome (p = 0.028). Higher inulin, FOS and pectin intake was associated with a shift in microbial taxa previously shown to be protective against CD onset in the GEM cohort; a reduction in Ruminococcus torques and an increase in NK4A214 group (phylum Firmicutes) presence (3.25×10⁻¹⁰<q<0.04).

Conclusion

This study demonstrates that dietary intake of fermentable fibre subtypes is associated with a reduced risk of CD development as well as with pleiotropic changes in CD risk biomarkers including microbiome, intestinal permeability, and subclinical inflammation. This suggests that the potential benefit of fermentable fibres on CD risk may involve changes in barrier function, and microbiome composition and function. Targeted interventions based on these findings could prove effective in preventing the onset of CD.