ZEPOSIA Proven Response & Remission at Weeks 10 and 52ab
The primary endpoint for the TRUE NORTH clinical trial was clinical remission at Week 10 and Week 52.
Patients experienced reliefc from symptoms as early as Week 21-3
A decrease in both RBS and
SFS was observed in
patients taking ZEPOSIA as
early as Week 22,4
Rapid clinical response (key secondary endpoint) at Week 104a
Long-term clinical remission data observed up to ~4 years5
aClinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1. Significantly higher clinical response rates vs placebo in the pivotal trial: 48% (205/429) vs 26% (56/216) at Week 10 (p<0.0001); 60% (138/230) vs 41% (93/227) at Week 52 (p<0.0001).4
bClinical remission is defined as RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability. Significantly higher clinical remission rates vs placebo in the pivotal trial: 18% (79/429) vs 6% (13/216) at Week 10 (p<0.0001); 37% (85/230) vs 19% (42/227) at Week 52 (p<0.0001).4
cSymptomatic clinical response was defined as a decrease from baseline in the combined 6-point SFS + RBS by ≥1 point and ≥30%, and a decrease of ≥1 point in RBS or an absolute RBS of ≤1 point.3
RBS=rectal bleeding subscore; SFS=stool frequency subscore.
Week 10 Induction Data
Post-hoc analysis: patients experienced reliefa from UC symptoms as early as 1 week after completing the 7-day dose titration1-3
A decrease in both RBS and SFS was observed in patients taking ZEPOSIA as early as Week 2.2,4
These post-hoc analyses were not prespecified.1
aSymptomatic clinical response is defined as a decrease from baseline in the combined 6-point SFS + RBS by ≥1 point and ≥30%, and a decrease of ≥1 point in RBS or an absolute RBS of ≤1 point.1,3
bData are based on the nonresponder imputation.3
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.1
AT=advanced therapy; EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Secondary Endpoint
ZEPOSIA delivers rapid clinical response at Week 104a
- In the all-patients group, 48% of patients taking ZEPOSIA achieved clinical response at Week 104
- In the moderate AT-naïve subgroup, 60% of patients taking ZEPOSIA had clinical response at Week 101
aClinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1.1,4
bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.1
Post-hoc analysis:
49% of nonrespondersd who entered the open-label extension at Week 10 after the
induction period observed symptomatic clinical response by Week 20e (open-label extension
Week 10)6
Symptomatic clinical response is defined as a reduction from baseline in the partial Mayo score of ≥1 point and ≥30% and a ≥1-point decrease in RBS or absolute RBS ≤1.1,3
Efficacy analyses of symptomatic response were not prespecified.1
dNonresponders were patients who did not achieve clinical response (defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1) on ZEPOSIA at Week 10 of induction and entered the OLE.4,6
eData are based on the nonresponder imputation.6
AT=advanced therapy; EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Primary Endpoint
ZEPOSIA delivers rapid clinical remission at Week 104a
- In the all-patients group, 18% of patients taking ZEPOSIA achieved clinical remission at Week 104
- In the moderate AT-naïve subgroup, 36% of patients taking ZEPOSIA had clinical remission at Week 101
aClinical remission is defined as RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability.1,4
bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.1
AT=advanced therapy; EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Secondary Endpoint
Patients taking ZEPOSIA saw significant endoscopic improvement at Week 104a
aEndoscopic improvement is defined as a Mayo endoscopy subscore of 0 or 1 without friability.1,4
bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.1
AT=advanced therapy; EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Secondary Endpoint
Patients taking ZEPOSIA saw significant EHMI at Week 104a
The relationship of EHMI, as defined in UC Study 1 at Week 10, to disease progression and long-term outcomes was not evaluated.4
aEHMI is defined as both a Mayo endoscopy subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, ie, Geboes <2.0).1,4
bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.1
AT=advanced therapy; EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Week 52 Maintenance Data
Secondary Endpoint
Increased rates of clinical response seen at Week 524a
- At Week 52, clinical response in the all-patients group was 60% for patients taking ZEPOSIA4
- Clinical response at Week 52 in the moderate AT-naïve subgroup was 67% for patients taking ZEPOSIA7
aClinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1.4,7
bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.7
AT=advanced therapy; CS=corticosteroid; EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Primary Endpoint
ZEPOSIA demonstrates sustained clinical remission at Week 524a
- At Week 52, clinical remission in the all-patients group was 37% for patients taking ZEPOSIA4
- At Week 52, clinical remission in the moderate AT-naïve subgroup was 47% for patients taking ZEPOSIA7
aClinical remission is defined as RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability.4,7
bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.7
AT=advanced therapy; CS=corticosteroid; EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Secondary Endpoint
ZEPOSIA can help patients achieve remission without the use of corticosteroids4a
- 32% of all patients on ZEPOSIA achieved CS-free remission at Week 524
- 43% of patients in the moderate AT-naïve subgroup had CS-free remission at Week 527
aCS-free remission is defined as clinical remission at Week 52 while off corticosteroids for ≥12 weeks.4,7
bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.7
AT=advanced therapy; CS=corticosteroid; EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Secondary Endpoint
Significant endoscopic improvement observed at Week 524a
- At Week 52, ZEPOSIA demonstrated endoscopic improvement in 46% of all patients4
- In the moderate AT-naïve subgroup, 54% of patients had endoscopic improvement at Week 527
aEndoscopic improvement is defined as a Mayo endoscopy subscore of 0 or 1 without friability.4,7
bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.7
AT=advanced therapy; CS=corticosteroid; EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Secondary Endpoint
Significant EHMI observed at Week 524a
- At Week 52 in the all-patients group, more patients on ZEPOSIA demonstrated endoscopic-histologic mucosal improvement compared to placebo4
- At Week 52 in the moderate AT-naïve subgroup, 40% of patients on ZEPOSIA had endoscopic-histologic mucosal improvement7
The relationship of EHMI, as defined in UC Study 2 at Week 52, to disease progression and long-term outcomes was not evaluated.4
aEHMI is defined as both a Mayo endoscopy subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, ie, Geboes <2.0).4,7
bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).4
cThe moderate AT-naïve subgroup included patients with a Mayo endoscopy subscore of 2.7
AT=advanced therapy; CS=corticosteroid; EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.
Long-Term Clinical Data Observed up to ~4 Years5
Clinical remissiona data up to 194 weeks in the open-label extension trial5
Data were analyzed in the ITT population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.8
In the NRI analysis of a subset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 65% (n=54/83) were in clinical remission at Week 98 (Week 46 of OLE), 51% (n=42/83) were in clinical remission at Week 146 (Week 94 of OLE), and 45% (n=37/83) were in clinical remission at Week 194 (Week 142 of OLE).5
Study Design for OLE
The TRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the phase 2 TOUCHSTONE OLE. A total of 823 patients from TRUE NORTH entered the TRUE NORTH OLE.8-10
Endpoints were evaluated at Weeks 46, 94, and 142 of the OLE for all patients who entered the OLE from the TRUE NORTH parent study and for a subset of patients in clinical remission or clinical response at Week 52 and had continuous ZEPOSIA exposure. Endpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission. Safety was evaluated for all 823 patients who entered the OLE from the TRUE NORTH parent study.8,9,11-13
These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.13
aClinical remission (3-component Mayo score) is defined as RBS=0, SFS ≤1 (and a decrease of ≥1 point from the baseline SFS), and endoscopy subscore ≤1.5
bThe OLE did not include a placebo comparator arm.5,14
CS=corticosteroid; ITT=intent-to-treat; NRI=nonresponder imputation; OC=observed case; RBS=rectal bleeding subscore; SFS=stool frequency subscore.
Clinical responsea data up to 194 weeks in the open-label extension trial5
Data were analyzed in the ITT population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.8
In the NRI analysis of a subset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure, 71% (n=93/131) were in clinical response at Week 98 (Week 46 of OLE), 57% (n=75/131) were in clinical response at Week 146 (Week 94 of OLE), and 53% (n=70/131) were in clinical response at Week 194 (Week 142 of OLE).5
Study Design for OLE
The TRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the phase 2 TOUCHSTONE OLE. A total of 823 patients from TRUE NORTH entered the TRUE NORTH OLE.8-10
Endpoints were evaluated at Weeks 46, 94, and 142 of the OLE for all patients who entered the OLE from the TRUE NORTH parent study and for a subset of patients in clinical remission or clinical response at Week 52 and had continuous ZEPOSIA exposure. Endpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission. Safety was evaluated for all 823 patients who entered the OLE from the TRUE NORTH parent study.8,9,11-13
These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.13
aClinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1.5
bThe OLE did not include a placebo comparator arm.5,14
CS=corticosteroid; ITT=intent-to-treat; NRI=nonresponder imputation; OC=observed case; RBS=rectal bleeding subscore; SFS=stool frequency subscore.
CS-free remissiona data up to 194 weeks in the open-label extension trial5
Data were analyzed in the ITT population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.8
In the NRI analysis of a subset of patients in CS-free remission at Week 52 and had continuous ZEPOSIA exposure, 64% (n=53/83) were in CS-free remission at Week 98 (Week 46 of OLE), 49% (n=41/183) were in CS-free remission at Week 146 (Week 94 of OLE), and 45% (n=37/83) were in CS-free remission at Week 194 (Week 142 of OLE).5
Study Design for OLE
The TRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the phase 2 TOUCHSTONE OLE. A total of 823 patients from TRUE NORTH entered the TRUE NORTH OLE.8-10
Endpoints were evaluated at Weeks 46, 94, and 142 of the OLE for all patients who entered the OLE from the TRUE NORTH parent study and for a subset of patients in clinical remission or clinical response at Week 52 and had continuous ZEPOSIA exposure. Endpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission. Safety was evaluated for all 823 patients who entered the OLE from the TRUE NORTH parent study.8,9,11-13
These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.13
aCS-free remission is defined as clinical remission at Week 52 while off corticosteroids for ≥12 weeks.5
bClinical remission is defined as RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability.4
cThe OLE did not include a placebo comparator arm.5,14
CS=corticosteroid; ITT=intent-to-treat; NRI=nonresponder imputation; OC=observed case; RBS=rectal bleeding subscore; SFS=stool frequency subscore.
Understand the Study Design
Review the Demonstrated Safety Profile4
References:
- Irving P, Long MD, Siegmund B, et al. Efficacy of ozanimod as an induction therapy in advanced therapy-naive ulcerative colitis patients suboptimally controlled on conventional treatments. Oral presentation at: United European Gastroenterology (UEG) Week 2023; Copenhagen, Denmark; October 14–17, 2023. Presentation OP133.
- Sandborn WJ, Feagan BG, D’Haens G, et al; True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis [supplementary appendix]. N Engl J Med. 2021;385(14):1280-1291.
- Siegmund B, Axelrad J, Pondel M, et al. Rapidity of ozanimod-induced symptomatic response and remission in patients with moderately to severely active ulcerative colitis: results from the induction period of True North. Oral presentation at: European Crohn’s and Colitis Organisation (ECCO) Virtual; February 16–19, 2022.
- Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2024.
- Data on File. BMS-REF-OZA-0066. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
- Panaccione R, Afzali A, Hudesman D, et al. Extended therapy with ozanimod for delayed responders to ozanimod in moderately to severely active ulcerative colitis: data from the True North open-label extension study. Poster presented at: Digestive Disease Week (DDW); San Diego, CA, and Virtual; May 21–24, 2022. Poster Tu1450.
- Siegmund B, Irving P, D’Haens G, et al. Ozanimod as a maintenance therapy in advanced therapy-naive ulcerative colitis patients with moderate vs severe endoscopic disease. Oral presentation at: United European Gastroenterology (UEG) Week 2023; Copenhagen, Denmark; October 14–17, 2023. Presentation OP135.
- Danese S, Colombel JF, Ponich T, et al. Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. Oral presentation at: ECCO 2022: February 16–19, 2022. Presentation DOP44.
- Danese S, Abreu MT, Wolf DC, et al. Efficacy and safety of 3 years of continuous ozanimod treatment: an interim analysis of the True North open-label extension study. Oral presentation at: European Crohn’s and Colitis Organisation (ECCO) 2023; Copenhagen, Denmark; March 1–4, 2023. Presentation DOP37.
- Sandborn WJ, Feagan BG, Hanauer S, et al. Long-term efficacy and safety of ozanimod in moderately to severely active ulcerative colitis: results from the open-label extension of the randomized, phase 2 TOUCHSTONE study. J Crohns Colitis. 2021;15(7):1120-1129.
- Panaccione R, Danese S, Wolf DC, et al. Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension. Poster presented at: European Crohn’s and Colitis Organisation (ECCO) 2023; Copenhagen, Denmark; March 1–4, 2023. Poster P405.
- Data on File. BMS_ZEP008535. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
- Wolf DC, Colombel JF, Ponich T, et al. Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. Poster presented at: Digestive Disease Week (DDW); San Diego, CA, and Virtual; May 21–24, 2022. Poster Tu1458.
- Danese S, Panaccione R, Abreu MT, et al. Efficacy and safety of approximately 3 years of continuous ozanimod in moderately to severely active ulcerative colitis: interim analysis of the True North open-label extension. J Crohns Colitis. Published online August 31, 2023. doi:10.1093/ecco-jcc/jjad146
