Well-established safety profile across multiple indicationsa

4 Clinical Trials, >1370 ZEPOSIA-Treated Patients Across Multiple Indications, >20,000 patient years of total exposure in clinical trials 4 Clinical Trials, >1370 ZEPOSIA-Treated Patients Across Multiple Indications, >20,000 patient years of total exposure in clinical trials

aZEPOSIA has been studied across multiple indications in 4 clinical trials, including TRUE NORTH (Ph 3); TOUCHSTONE (Ph 2); and SUNBEAM (Ph 3) and RADIANCE (Ph 3). 496 patients receiving the 0.92-mg dose of ZEPOSIA during induction in TRUE NORTH or TOUCHSTONE and 882 patients receiving the 0.92-mg dose of ZEPOSIA in SUNBEAM or RADIANCE were assessed in the safety analysis.1

*MS: Includes Phase 1, Phase 2, SUNBEAM, RADIANCE, and DAYBREAK (data cutoff: February 2, 2021). UC: Includes TOUCHSTONE, TRUE NORTH, TRUE NORTH OLE (data cutoff: September 30, 2020). Post-marketing Setting: data cutoff November 19, 2021. Exposure for patients with MS in clinical trials is 2631 patients and 11,938 patient-years. Exposure for patients with UC in clinical trials is 1158 patients and 2108 patient-years. Exposure for patients in the post-marketing setting across indications is 9738 patients and 6455 patient-years2-4

Adverse Reactions With an Incidence of at Least 2% in ZEPOSIA-Treated Patients and at
Least 1% Greater Than Placebo in Patients With Ulcerative Colitis
(Pooled Induction Periods UC Study 1 and Study 3)1b
Adverse Reaction
ZEPOSIA 0.92 mg
(n=496)e,f
Placebo
(n=281)f
Upper Respiratory Infectionc 5% 4%
Liver Test Increasedd 5% 0%
Headache 4% 3%
Pyrexia 3% 2%
Nausea 3% 2%
Arthralgia 3% 1%

UC Study 3 (8-week induction): TOUCHSTONE is a Phase 2, multi-center, randomized, double-blind, placebo controlled parallel-group study to evaluate the clinical efficacy and safety of induction therapy with RPC1063 in 199 patients with moderately to severely active ulcerative colitis. Participants who completed the induction period and were responders at Week 8, continued to receive the same dose of ozanimod during the maintenance period up to Week 32.

For full study design of UC Study 1 and Study 2, click here.

  • bAdditional 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.1
  • cIncludes 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.1
  • dIncludes 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, transaminases increased.1
  • eZEPOSIA was initiated with a 7-day titration.1
  • fPercentages were calculated as the sum of each individual study percentage multiplied by its Cochran-Mantel-Haenszel weight.1
Adverse Events from TRUE NORTH (UC Study 1) Induction Period5
ZEPOSIA 0.92 mg
(n=429)
Placebo
(n=216)
Adverse Event 40.1% 38%
Serious Adverse Event 4% 3.2%
Adverse Reactions With an Incidence of at Least 4% in ZEPOSIA-Treated Patients and at Least 1% Greater Than Placebo in Patients With Ulcerative Colitis. Maintenance period
(UC Study 2)1
Adverse Reaction
ZEPOSIA 0.92 mg
(n=230)
Placebo
(n=227)
Liver Test Increasedg 11% 2%
Headache 5% <1%

gIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, blood bilirubin increased, liver function test increased, blood alkaline phosphatase increased.1

Adverse Events from TRUE NORTH (UC Study 2) Maintenance Period5
ZEPOSIA 0.92 mg
(n=230)
Placebo
(n=227)
Adverse Event 49.1% 36.6%
Serious Adverse Event 5.2% 7.9%

MS=multiple sclerosis; OLE=open-label extension; UC=ulcerative colitis.

UC Study 1 and Study 2
Adverse Reaction
Induction
Maintenance
ZEPOSIA
0.92 mg
(n=429)
Placebo
(n=216)
ZEPOSIA
0.92 mg
(n=230)
Placebo
(n=227)
ALT ≥3x ULN
2.6% 0.5% 2.3% 0%
ALT ≥5x ULN
0.9% 0.5% 0.9% 0%
  • In controlled and uncontrolled UC studies, the majority (96%) of patients with ALT >3X ULN continued treatment with ZEPOSIA, with values returning to <3X ULN within ~2-4 weeks1
  • The overall 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 studies1
  • Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine, should have hepatic enzymes checked, and ZEPOSIA should be discontinued if significant liver injury is confirmed1

ALT=alanine aminotransferase; LFT=liver function test; ULN=upper limit of normal.

In controlled clinical trials with ZEPOSIA, mean lymphocyte counts decreased to approximately 45% of baseline at 3 months (approximate mean blood lymphocyte counts 0.8 x 109/L), and low lymphocyte counts were maintained during treatment with ZEPOSIA.1

  • The proportion of patients treated with ZEPOSIA with lymphocytes less than 0.2 x 109/L was 2.0% in UC Study 1 and Study 3 (phase 2) and 2.3% in UC Study 21
  • These values generally returned to greater than 0.2 x 109/L while patients remained on treatment with ZEPOSIA1
  • After discontinuing treatment, the median time for peripheral blood lymphocytes to return to the normal range was approximately 30 days1
    • Approximately 80% to 90% of patients were in the normal range within 3 months1
Pooled Analysis of Controlled and Uncontrolled Trials6
Pooled Analysis of Controlled and Uncontrolled Trials: Mean Absolute Lymphocyte Count by Visit Pooled Analysis of Controlled and Uncontrolled Trials: Mean Absolute Lymphocyte Count by Visit
  • Descriptive pooled analysis of controlled and uncontrolled trials including the 32-week phase 2 TOUCHSTONE trial, the 52-week phase 3 TRUE NORTH trial, and an open-label extension study. Patients completing ≥1 year of the TOUCHSTONE open-label extension study (OLE) could roll over into the TRUE NORTH OLE6
  • Reductions in ALC were observed at Week 5 (the first post-baseline assessment) and sustained through treatment6
  • 60 patients (5.3%) had ALC <0.2 x 109/L at least once during ZEPOSIA treatment6
    • Most patients (98.3%; n=59) returned to ALC ≥0.2 x 109/L at the time of the analysis; 89.8% returned to ≥0.2 x 109/L while continuing treatment with ZEPOSIA6

Patients may be included in both placebo and ZEPOSIA treatment groups. The total count in the placebo group includes 227 patients who were treated with ZEPOSIA in the induction period and were re-randomized to placebo in the maintenance period of TRUE NORTH.6

ALC=absolute lymphocyte count.

Low Discontinuation Rates

Discontinuation Rates Due
to TEAEs That Are Comparable
to Placebo

Overall Discontinuation Rates5

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)5

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 treatment1,7

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 studies1

TEAEs=treatment-emergent adverse events.

Infections and Malignancies

Rates of Serious Infection Were Low and Comparable to Placebo in Clinical Trials1

Rates of Serious Infection in
Clinical Trials1
Inductionb
Maintenance
Infection
ZEPOSIA 0.92 mg
(n=496)
Placebo
(n=281)
ZEPOSIA 0.92 mg
(n=230)
Placebo
(n=227)
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 modulator1
  • bAdditional 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.1
Rates of Malignancies in Clinical Trials
Induction
Maintenance5
Malignancies
Malig-
nancies
ZEPOSIA 0.92 mg
(n=429)
Placebo
(n=216)
ZEPOSIA 0.92 mg
(n=230)
Placebo
(n=227)
Basal Cell
Carcinoma
0% 0% 0.4% 0%
Rectal Adenocar-
cinoma
0% 0% 0.4% 0%
Adenocar-
cinoma Of
The Colon
0% 0% 0% 0.4%
Breast
Cancer
0% 0% 0% 0.4%
Infections and Malignancies Across All UC Trials With ZEPOSIA8
ZEPOSIA 0.92 mg
(n=1158)
PY=1922.5i
Placebo
(n=508)
PY=249.2i
% (n) IR, per 100 PYj % (n) IR, per 100 PYj
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
Malignan-
cies
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 trialk (phase 2), 52-week TRUE NORTH trial (phase 3), and the respective open-label extension 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
  • iTotal patient-years 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
  • jIncidence rate per 100 patient-years, 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
  • kTOUCHSTONE patients randomized to ZEPOSIA 0.46 mg unapproved dose were only analyzed upon entering TOUCHSTONE OLE and receiving daily ZEPOSIA 0.92 mg.8

IR=incidence rate; PT=preferred term; PY=patient years; S1P=sphingosine 1-phosphate; SOC=system organ class.

Open-Label Extension Safety in TRUE NORTH Patients9

This safety analysis includes patients (N=823) with UC from the TRUE NORTH parent study who entered the TRUE NORTH OLE

Safety from All TRUE NORTH Patients in OLE (N=823)
Adverse
Events
All Patients in OLE
(N=823)
% (N)
EAIR per
100
Patient-YearsPY
Adverse Events (AEs)l 75.3% (620) 102.64
Serious Adverse Eventsl 12.8% (105) 7.33
AEs Leading to Discontinuation
of ZEPOSIA
4.7% (39) 2.55
Most Frequent Adverse Eventsm
Lymphopenia 13.1% (108) 7.70
Nasopharyngitis 8.9% (73) 5.10
Anemia 8.6% (71) 4.92
Lymphocyte Count Decreasedn 8.3% (68) 4.66
Alanine Aminotransferase Increasedn 7.8% (64) 4.43
Arthralgia 6.4% (53) 3.64
Headache 6.4% (53) 3.62
Gamma-glutamyl Transferase Increasedn 4.6% (38) 2.57
Hypertension 4.5% (37) 2.47
Back Pain 3.3% (27) 1.80
Infectiono 35.0% (288) 25.76
Serious Infection 2.7% (22) 1.45
Nasopharyngitis 8.9% (73) 5.10
Upper Respiratory Tract Infection 6.0% (49) 3.33
Herpes Zoster Infection 3.2% (26) 1.72
Sinusitis 2.8% (23) 1.53
Bronchitis 2.8% (23) 1.53
Cancer 1.0% (8) 0.521
Basal Cell Carcinoma 0.5% (4) 0.261
Rectal Adenocarcinoma 0.2% (2) 0.129
Lung Neoplasm Malignant 0.1% (1) 0.065
Breast Cancer 0.1% (1) 0.065
Laboratory Assessmentsp
Alanine Aminotransferase (ALT)
≥3x ULN 5.5%
(45/817)
NR
≥5x ULN 1.7%
(14/817)
NR

Data cutoff: September 30, 2020.

  • lAll AEs and SAEs listed were treatment emergent.9
  • mThe most frequent events were defined as those that occurred in at least 5% of the patients who received ozanimod in either the OLE study population or the subgroup who entered the study in clinical response.9
  • nLaboratory values were flagged by the central laboratory if they fell outside the standard reference range. The investigator decided whether the laboratory value qualified as an adverse event.9
  • oInfectious TEAEs that occurred in at least 3% of the patients who received ozanimod in either the OLE study population or the subgroup who entered the study in clinical response are listed.9
  • pPatients were included if their laboratory values met these cut-offs at any point in the study. The denominator shows the number of evaluable patients.9

EAIR=exposure-adjusted incidence rate; NR=not reported; SAE=serious adverse event; TEAE=treatment-emergent adverse event; UC=ulcerative colitis; ULN=upper limit of normal.

Explore the Efficacy
Data for ZEPOSIA

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 Design

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