New Duvakitug Data at ECCO

These results were shared in two oral presentations at the 20th Congress of the European Crohn’s and Colitis Organisation (ECCO) in Berlin, Germany.

Ulcerative colitis
In the UC cohort of the RELIEVE UCCD study, 36% (450 mg dose) and 48% (900 mg dose) of patients treated with duvakitug achieved the primary endpoint of clinical remission (mMS) at week 14 compared to 20% treated with placebo; placebo-adjusted rates were 16% (450 mg dose) and 27% (900 mg dose) (p=0.050 and 0.003, respectively). In addition, higher clinical remission rates were observed for both doses of duvakitug versus placebo in both advanced therapy (AT) -experienced and AT-naïve subgroups of patients: i) AT-experienced: 29% (450 mg) and 36% (900 mg), with placebo-adjusted rates of 22% (450 mg) and 29% (900 mg). ii) AT-naïve: 39% (450 mg) and 53% (900 mg), with placebo-adjusted rates of 12% (450 mg) and 26% (900 mg).

Additional endpoints observed: i) Clinical response (mMS): 81% (450 mg) and 70% (900 mg) compared to 52% treated with placebo. ii) Endoscopic improvement (MES): 45% (450 mg) and 50% (900 mg) compared to 23% treated with placebo. iii) Histological-endoscopic mucosal improvement (HEMI): 30% (450 mg) and 33% (900 mg) compared to 16% treated with placebo.

Walter Reinisch, MD, PhD, Medical University of Vienna, and lead investigator of the RELIEVE UCCD study: “Patients, many of whom have spent years in a recurring cycle of remission and relapse, have been waiting a long time for better options in treating ulcerative colitis. We’re highly encouraged by the significant treatment response, compared to placebo, seen in the study, both in advanced therapy naïve-and experienced patients,” said Walter Reinisch, MD, PhD, Medical University of Vienna, and lead investigator of the RELIEVE UCCD study. “With this potential of duvakitug to reduce inflammation, we could truly transform treatment for patients with IBD in a safe manner.”

Crohn’s disease
In the CD cohort of the RELIEVE UCCD study, 26% (450 mg dose) and 48% (900 mg dose) of patients treated with duvakitug achieved the primary endpoint of endoscopic response (SES-CD) compared to 13% on placebo; placebo-adjusted rates were 13% (450 mg dose) and 35% (900 mg dose) at week 14 (p= 0.058 and <0.001, respectively).

In addition, higher endoscopic response rates were observed for both doses of duvakitug versus placebo in both AT-experienced and AT-naïve subgroups of patients: i) AT-experienced: 11% (450 mg) and 48% (900 mg), with placebo-adjusted rates of 7% (450 mg) and 44% (900 mg). ii) AT-naïve: 47% (450 mg) and 47% (900 mg), with placebo-adjusted rates of 25% (450 mg) and 25% (900 mg).

Additional endpoints observed: i) Endoscopic remission (SES-CD): 17% (450 mg) and 26% (900 mg) compared to 9% treated with placebo. ii) Clinical remission (CDAI): 50% (450 mg) and 54% (900 mg) compared to 41% treated with placebo. iii) Clinical response (CDAI): 61% (450 mg) and 62% (900 mg) compared to 41% treated with placebo. iv) Clinical response (PRO2): 50% (450 mg) and 53% (900 mg) compared to 29% treated with placebo.

Vipul Jairath, MBChB, DPhil, FRCP, FRCPC Professor of Medicine in the Departments of Medicine, Epidemiology and Biostatistics at Western University, and lead investigator of the RELIEVE UCCD study: “Every day, I see patients with Crohn’s disease who continue to suffer from the often-severe symptoms of the disease despite available treatments,” said Vipul Jairath, MBChB, DPhil, FRCP, FRCPC, Professor of Medicine in the Departments of Medicine, Epidemiology and Biostatistics at Western University, and lead investigator of the RELIEVE UCCD study. “The endoscopic response rates seen in this study support the potential of duvakitug as an effective new option for those who are in desperate need of relief.”

RELIEVE UCCD safety data summary
In both the UC and CD cohorts, duvakitug was generally well tolerated with no emergent safety signals observed. No dose-dependent or adverse event (AE) pattern was observed for treatment-related AEs, serious adverse events (SAEs), AEs leading to discontinuation or adverse events of special interest (AESIs).

Duvakitug is currently under clinical investigation, and its efficacy and safety have not been evaluated by any regulatory authority.

About the RELIEVE UCCD phase IIb study - RELIEVE UCCD was a 14-week phase IIb, randomized, double-blinded, dose-ranging study to determine the efficacy, safety, pharmacokinetics, and tolerability of duvakitug in adults with moderate-to-severe UC or CD. The study was an innovative and efficient basket study design allowing the inclusion of patients with either type UC and CD. It is also the first and only randomized, blinded and placebo-controlled phase 2 study to investigate the impact of TL1A in CD.

In the study, patients who met pre-specified inclusion criteria were randomized to receive one of two duvakitug doses or placebo, administered every two weeks subcutaneously, in a 1:1:1 ratio for each indication (UC or CD) stratified by previous exposure to advanced IBD therapies for 14 weeks. The UC cohort comprised adults with moderately to severely active disease with inadequate response, loss of response or intolerance to previous conventional and/or advanced therapies (AT). The CD cohort comprised adults with moderately to severely active disease with documented inadequate response, loss of response or intolerance to conventional and/or ATs.

Primary efficacy endpoints are the number of participants who showed clinical remission (as defined by the modified Mayo score) in the UC cohort or the number of participants who showed endoscopic response (as defined by the SES-CD endoscopic score for CD) in the CD cohort. The study included sites in the US, Europe, Israel, and Asia.