| Adverse Reaction | ZEPOSIA 0.92 |
Placebo |
| Upper Respiratory Infectione | 5% | 4% |
| Liver Test Increasedf | 5% | 0% |
| Headache | 4% | 3% |
| Pyrexia | 3% | 2% |
| Nausea | 3% | 2% |
| Arthralgia | 3% | 1% |
ZEPOSIA Offers Patients a Demonstrated Safety Profile
Low discontinuation rates
due to treatment-emergent adverse events that are comparable to placebo1a
Rates of serious infection were low and comparable to placebo in clinical trials2bc
Demonstrated safety profile
and long-term safety data observed for over 4 years1-3
aOverall rates of discontinuation were 6.5% with ZEPOSIA (N=429) vs 11.1% with placebo (N=216) in the induction phase, and 20% with ZEPOSIA (N=230) vs 45.4% with placebo (N=227) in the maintenance phase. Discontinuation rates due to TEAEs in induction were 3.3% for patients taking ZEPOSIA vs 3.2% for patients taking placebo. In maintenance, TEAE discontinuation rates were 1.3% for patients taking ZEPOSIA vs 2.6% for patients taking placebo.1,2
bOverall rates of infection were 9.9% with ZEPOSIA (N=496) vs 10.7% with placebo (N=281) in the induction phase, and 23% with ZEPOSIA (N=230) vs 12% with placebo (N=227) in the maintenance phase. Serious infection rates in the induction phase (UC Study 1 and UC Study 3/TOUCHSTONE) were 0.8% with ZEPOSIA vs 0.4% with placebo. Serious infection rates in the maintenance phase were 0.9% with ZEPOSIA vs 1.8% with placebo.2
cAdditional data from the induction period of a randomized, double-blind, placebo-controlled study (UC Study 3/TOUCHSTONE) included 67 patients who received ZEPOSIA 0.92 mg once daily.2
Adverse Reactions With an Incidence of at Least 2% in ZEPOSIA-Treated Patients and at Least 1% Greater Than Placebo in Patients With UC (Pooled UC Study 1 and Study 3)2
Induction (UC Study 1 and Study 3)d
Adverse Reactions With an Incidence of at Least 4% in ZEPOSIA-Treated Patients and at Least 1% Greater Than Placebo in Patients With UC (UC Study 2)2
Maintenance (UC Study 2)
| Adverse Reaction | ZEPOSIA 0.92 mg |
Placebo |
| Liver Test Increasedi | 11% | 2% |
| Headache | 5% | <1% |
dAdditional data from the induction period of a randomized, double-blind, placebo-controlled study (UC Study 3/TOUCHSTONE) included 67 patients who received ZEPOSIA 0.92 mg once daily2
eIncludes the following terms: streptococcal pharyngitis, pharyngotonsillitis, bacterial pharyngitis, nasopharyngitis, upper respiratory tract infection, pharyngitis, sinusitis, tonsillitis, viral upper respiratory tract infection, laryngitis, acute sinusitis, catarrh, chronic sinusitis, upper respiratory tract inflammation, chronic tonsillitis, viral pharyngitis, viral sinusitis, bacterial sinusitis, bacterial upper respiratory tract infection, viral labyrinthitis, laryngeal inflammation, and pharyngeal inflammation.2
fIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, liver function test increased, blood alkaline phosphatase increased, and transaminases increased.2
gPercentages were calculated as the sum of each individual study percentage multiplied by its Cochran-Mantel-Haenszel weight.2
hZEPOSIA was initiated with a 7-day titration.2
iIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, liver function test increased, and blood alkaline phosphatase increased.2
UC Study 3 (8-week induction): TOUCHSTONE is a phase 2, multicenter, randomized, double-blind, placebo-controlled parallel-group study to evaluate the clinical efficacy and safety of induction therapy with ZEPOSIA in 199 patients with moderately to severely active UC. Participants who completed the induction period and were responders at Week 8 continued to receive the same dose of ZEPOSIA during the maintenance period up to Week 32.4
For full study design of UC Study 1 and Study 2, click here.
Adverse Events From TRUE NORTH (UC Study 1) Induction Period1
ZEPOSIA 0.92 mg |
Placebo |
|
| Adverse Event | 40.1% | 38% |
| Serious Adverse Event | 4% | 3.2% |
Adverse Events From TRUE NORTH (UC Study 2) Maintenance Period1
ZEPOSIA 0.92 mg |
Placebo |
|
| Adverse Event | 49.1% | 36.6% |
| Serious Adverse Event | 5.2% | 7.9% |
In ZEPOSIA-treated patients, rates of thromboembolic events or major adverse cardiac events were similar to patients treated with placebo in TRUE NORTH.5jk
jIn the TRUE NORTH phase 3 studies, 1 case of ischemic stroke (0.2%) was reported in ZEPOSIA-treated patients vs no reports in patients treated with placebo.5
kThromboembolic events include pulmonary embolism and venous arterial thrombosis. Major or adverse cardiac events include cardiovascular death, myocardial infarction, and stroke.5
TEAE=treatment-emergent adverse event; UC=ulcerative colitis.
Low Discontinuation Rates
Discontinuation Rates Due to TEAEs That Are Comparable to Placebo1
Overall Discontinuation Rates1
UC Study 1—Induction:
6.5% for ZEPOSIA | 11.1% for Placebo
UC Study 2—Maintenance:
20.0% for ZEPOSIA | 45.4% for Placebo
Discontinuation Rates Due to Treatment-Emergent Adverse Events (TEAEs)1
Induction
3.3%
ZEPOSIA
vs 3.2%
for placebo
Maintenance
1.3%
ZEPOSIA
vs 2.6%
for placebo
One case of macular edema was reported during the maintenance phase in 1 person with preexisting risk factors at baseline; it resolved after discontinuation of treatment.1,7
Overall, the discontinuation rate because of elevations in hepatic enzymes was 0.4% in patients treated with ZEPOSIA 0.92 mg and none in patients who received placebo in the controlled UC studies.2
TEAEs=treatment-emergent adverse events; UC=ulcerative colitis.
Infections and Malignancies
Rates of Serious Infection Were Low and Comparable to Placebo in Clinical Trials2
Rates of Serious Infection in Clinical Trials2
| Inductionm | Maintenance |
Infection |
ZEPOSIA 0.92 mg |
Placebo |
ZEPOSIA 0.92 mg |
Placebo |
Overall Rate of Infection |
9.9% | 10.7% | 23% | 12% |
Serious Infections |
0.8% | 0.4% | 0.9% | 1.8% |
Herpes Zoster |
0.4% | 0% | 2.2% | 0.4% |
- Malignancies, such as melanoma, basal cell carcinoma, breast cancer, seminoma, cervical carcinoma, and adenocarcinomas, including rectal adenocarcinoma, were reported with ZEPOSIA in controlled trials of multiple sclerosis and UC. An increased risk of cutaneous malignancies has been reported with another S1P receptor modulator2
mAdditional data from the induction period of a randomized, double-blind, placebo-controlled study (UC Study 3/TOUCHSTONE) included 67 patients who received ZEPOSIA 0.92 mg once daily.2
Rates of Malignancies in Clinical Trials1
| Induction | Maintenance |
Malignancies |
ZEPOSIA 0.92 mg |
Placebo |
ZEPOSIA 0.92 mg |
Placebo |
Basal Cell Carcinoma |
0% | 0% | 0.4% | 0% |
Rectal Adenocarcinoma |
0% | 0% | 0.4% | 0% |
Adenocarcinoma of |
0% | 0% | 0% | 0.4% |
Breast |
0% | 0% | 0% | 0.4% |
Infections and Malignancies Across All UC Trials With ZEPOSIA8
| ZEPOSIA 0.92 mg (n=1158) PY=1922.5n |
Placebo (n=508) PY=249.2n |
|
%(n) |
IR, per 100 PYo | %(n) | IR, per 100 PYo |
Any Infection |
29.1 (337) | 22.81 | 14.0 (71) | 31.43 |
Any Serious Infection |
2.2 (25) | 1.32 | 1.4 (7) | 2.84 |
Malignancies |
1.0 (12) | 0.63 | 0.4 (2) | 0.81 |
- Safety outcomes were analyzed using descriptive statistics on pooled data from all controlled and uncontrolled UC trials: participants from 32-week TOUCHSTONE trialp (phase 2), 52-week TRUE NORTH trial (phase 3), and the respective OLE trials8
- Median treatment duration in weeks for ZEPOSIA 0.92 mg and placebo was 65.79 and 17.21, respectively8
- TEAEs identified in the pooled data from all controlled and uncontrolled UC trials were consistent with the controlled UC trials8
nTotal PY equals the sum of the number of years on study contributed by each patient from time of first dose per treatment group in the pool to last date on study per treatment group in the pool. The algorithm for the last date on study is dependent on patient disposition and whether the patient enrolled into an extension study.8
oIncidence rate per 100 PY, calculated as number of patients/PY x 100 for specific SOC category or PT subcategory. Analysis was based on the treatment group to which a patient was assigned when the event occurred, including patients who were re-randomized to placebo.8
pTOUCHSTONE patients randomized to ZEPOSIA 0.46 mg unapproved dose were only analyzed upon entering TOUCHSTONE OLE and receiving daily ZEPOSIA 0.92 mg.9
IR=incidence rate; OLE=open-label extension; PT=preferred term; PY=patient-years; S1P=sphingosine 1-phosphate; SOC=system organ class; TEAE=treatment-emergent adverse event; UC=ulcerative colitis.
Long-Term Safety Data Observed Over ~4 Years With ZEPOSIA3,10
This Safety Analysis Includes Patients With UC From the TRUE NORTH Parent Study Who Entered the TRUE NORTH OLE for up to 194 Weeks of ZEPOSIA Exposure10
Safety From All TRUE NORTH Patients in OLE (N=823)10,11
| Adverse Events | All Patients in OLE (N=823) |
|---|---|
| EAIR per 100 PYq | |
| TEAEs | 85.5 |
| Serious TEAEs | 7.0 |
| TEAEs Leading to Treatment Discontinuation | 2.5 |
| Most Frequent TEAEs (Occurring in ≥8% of Patients) | |
| Lymphopeniar | 6.1 |
| COVID-19 | 4.3 |
| Nasopharyngitis | 3.8 |
| Anemiar | 3.7 |
| Lymphocyte Count Decreasedr | 3.7 |
| Alanine Aminotransferase Increasedr | 3.2 |
| Arthralgia | 3.2 |
| Headache | 2.8 |
| Infection (Occurring in ≥3.0% of Patients) | |
| COVID-19 | 4.3 |
| Nasopharyngitis | 3.8 |
| Upper Respiratory Tract Infection | 2.4 |
| Serious Infection | 1.8 |
| Herpes Zoster | 1.2 |
| Sinusitis | 1.2 |
| Bronchitis11 | 1.1 |
| Influenza11 | 1.0 |
| Malignancy (Serious TEAE)11 | |
| Basal Cell Carcinoma | 0.04 |
| Colon Adenocarcinoma | 0.04 |
| Pancreatic Adenocarcinoma | 0.04 |
| B-Cell Lymphoma | 0.04 |
| Follicular Lymphoma, Stage IV | 0.04 |
| Malignant Lung Neoplasm | 0.04 |
| Prostate Cancer | 0.04 |
| Rectal Adenocarcinoma | 0.04 |
| Rectal Cancer Stage II | 0.04 |
| Cardiovascular Disorders | |
| Hypertension | 2.3 |
| Hypertensive Crisis | 0.16 |
| Bradycardia | 0.12 |
| Myocardial Ischemia | 0.12 |
| Ischemic Stroke | 0.12 |
| Pulmonary Embolism | 0.12 |
| Deep Vein Thrombosis | 0.12 |
| Third-Degree AV Block | 0.04 |
| Macular Edema | 0.2 |
Three deaths were reported during the OLE: 1 sudden death, 1 due to COVID-19, and 1 due to adenocarcinoma.
These deaths were deemed to be unrelated to ZEPOSIA treatment by investigators.3,10
Infection (Occurring in ≥3.5% of Patients)10
COVID-19:
4.3 EAIR per 100 PYq
Nasopharyngitis:
3.8 EAIR per 100 PYq
Upper Respiratory Tract Infection:
2.4 EAIR per 100 PYq
qEAIRs were calculated as numbers of patients/PY × 100.10
rLaboratory values were flagged by the central laboratory if they fell outside the standard reference range; investigators decided whether laboratory values qualified as adverse events.12
AV=atrioventricular; EAIR=exposure-adjusted incidence rate; OLE=open-label extension; PY=patient-years; TEAE=treatment-emergent adverse event; UC=ulcerative colitis.
Explore the Efficacy Data for ZEPOSIA
Understand the Study
Design
References:
- Sandborn WJ, Feagan BG, D’Haens G, et al; True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385(14):1280-1291.
- Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2024.
- 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.
- Efficacy and safety study of ozanimod in ulcerative colitis (Touchstone). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT01647516. Updated May 19, 2021. Accessed July 26, 2023.
- Long M, Cross RK, Lichtenstein GR, et al. Long-term cardiac safety of ozanimod in phase 3 clinical program of ulcerative colitis and relapsing multiple sclerosis. Presented at: Digestive Disease Week (DDW); San Diego, CA, and Virtual; May 21–24, 2022. Presentation 15.
- Rieder F, Wolf DC, Charles L, Kollengode K, Patel A, Ghosh S. Incidence of infections in patients with moderately to severely active ulcerative colitis treated with ozanimod and relationship to significant lymphopenia: results from a pooled safety analysis. Poster presented at: DDW 2021 Virtual Digestive Disease Week; May 21–23, 2021.
- Danese S, Feagan BG, Wolf DC. Ozanimod as maintenance therapy in patients with moderate-to-severe ulcerative colitis: results from the phase 3, randomized, double-blind, placebo-controlled True North study. Paper presented at: United European Gastroenterology Week Virtual 2020; October 10–14, 2020. Presentation LB10.
- D’Haens G, Colombel JF, Lichtenstein GR, et al. Safety of ozanimod in patients with moderately to severely active ulcerative colitis over time: pooled analysis from phase 2, phase 3, and open-label extension trials. Oral presentation at: DDW 2021 Virtual Digestive Disease Week; May 21–23, 2021.
- 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.
- Siegel CA, Danese S, Rubin DT, et al. Safety of long-term ozanimod treatment for up to 4 years in patients with moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension. Oral presentation at: European Crohn's and Colitis Organisation (ECCO) 2024; Stockholm, Sweden; February 21–24, 2024.
- Data on File. BMS-REF-OZA-0066. 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.
