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Data in Early RMS: ENLIGHTEN Study

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ZEPOSIA was evaluated in 2 pivotal trials, SUNBEAM (1 year; N=1346) and RADIANCE (2 years; N=1313), that were multicenter, randomized, double-blind, double-dummy, active treatment-controlled studies of daily oral ozanimod 0.46 mg (not approved for maintenance dose) or 0.92 mg oral daily dose vs weekly Avonex (interferon beta-1a), 30-μg intramuscular injection. Please see study results below.1-3

The ENLIGHTEN Trial Is an Ongoing Post-Marketing Study Focused on Early RMS Patients4,5:

ENLIGHTEN Is an Ad Hoc, Open-Label, Single-Arm, Phase 3b/4, Ongoing Post-Marketing Study With 1-Year Interim Analysis* Results Presented at ECTRIMS 2023

ENLIGHTEN Study Design4,5

Graphic depicting the ENLIGHTEN study design Graphic depicting the ENLIGHTEN study design

Primary endpoint:

Clinically meaningful increase in cognitive processing speed, as measured by the SDMTa


Key secondary
endpoints:

  • Annual relapse rate
  • MRI lesions
  • Brain volume loss
  • Adverse events
Endpoints in the ENLIGHTEN study were analyzed descriptively.
Key Baseline Characteristics: 72.4% DMT naïve, 1.1 Mean years since RMS Diagnosis, 2.0 Median EDSS Key Baseline Characteristics: 72.4% DMT naïve, 1.1 Mean years since RMS Diagnosis, 2.0 Median EDSS
*Interim analysis period, data cutoff: February 14, 2023.4
aENLIGHTEN primary endpoint: proportion of patients with an increase in SDMT score ≥4 points or ≥10% from baseline to Year 1. The SDMT pairs a series of symbols with digits, and patients must match the appropriate symbol to the paired numerical digit using a key; the SDMT is administered orally in ENLIGHTEN. Scoring is based on the correct number of responses given in 90 seconds, with higher scores indicating faster processing.4

ENLIGHTEN Trial Inclusion Criteria1:

  • Aged 18-65 years at screening
  • Diagnosis of MS per the 2010 or 2017 revised McDonald criteria within the last 5 years
  • ≤1 MS disease-modifying therapy (none within 1 month of enrollment)
  • EDSS score of ≤3.5 at screening
  • No relapses within 30 days before screening
  • ≤10 GdE lesions on baseline brain MRI scan
  • No history of developmental disorders or motor or sensory defects that could interfere with cognitive test performance
ZEPOSIA pivotal trials SUNBEAM (1 year; N=1346) and RADIANCE (2 years; N=1313). Primary endpoint: ZEPOSIA reduced ARR vs Avonex by 48% at 1 year (0.181 vs 0.350, respectively) and by 38% at 2 years (0.172 vs 0.276, respectively). Secondary endpoints: ZEPOSIA reduced the number of new or enlarging T2 lesions by 48% at 1 year and by 42% at 2 years, and reduced the number of GdE lesions vs Avonex by 63% at 1 year and 53% at 2 years. 9 of 10 patients showed no confirmed 3-month disability progression. There was no significant difference in 3-month confirmed disability between ZEPOSIA and Avonex.1-3,7,8
ARR=annualized relapse rate; BVL=brain volume loss; DMT=disease-modifying therapy; EDSS=Expanded Disability Status Scale; GdE=gadolinium enhancing; MRI=magnetic resonance imaging; MS=multiple sclerosis; RMS=relapsing multiple sclerosis; SDMT=Symbol Digit Modalities Test.
Ad Hoc, Interim Analysis of Cognitive Processing Speed (SDMT) From ENLIGHTEN at 1 Year4

Patients Included in the Trial Had Been Diagnosed With MS for an Average of 1.1 Years6

Chart depicting Categorical Analysis of Cognitive Processing of Speed Data from ENLIGHTEN Chart depicting Categorical Analysis of Cognitive Processing of Speed Data from ENLIGHTEN

The SDMT assesses cognitive processing speed.9

In ENLIGHTEN, an SDMT score change of ≥4 points, or ≥10% from baseline, is considered clinically meaningful.4

Endpoints were analyzed descriptively.
bThe binary response (yes/no) to improvement in SDMT score was fitted on the observed data using a generalized estimating equation approach with a logit link including baseline SDMT value, baseline age, baseline whole brain volume, and time point (as a categorical variable).4
cImproved: at least a 4-point or 10% increase in SDMT relative to baseline; stable: change from baseline SDMT between −4 and 4 points and percentage change between −10% and 10%; worsened: at least a 4-point or 10% decrease in SDMT relative to baseline.4
In a post hoc analysis of SUNBEAM pivotal trial, 77% of patients on ZEPOSIA were categorized as improved or remained stable in SDMT scores at 1 year (23% of patients were categorized as worsened). Please note BVL and SDMT endpoints were not part of the statistical analysis hierarchy.1-3,7,8
Interim Analysis of Brain Volume Loss From ENLIGHTEN at 1 Year5

Patients Included in the Trial Had Been Diagnosed With MS for an Average of 1.1 Years6

Mean Percentage Change From Baseline (Interim Analysis)5

Chart depicting the mean percentage change from baseline (interim analysis) Chart depicting the mean percentage change from baseline (interim analysis)
Endpoints were analyzed descriptively.
In the ZEPOSIA pivotal trials, volume loss endpoints were measured as relative reduction in mean percent change from baseline vs Avonex at 1 year (SUNBEAM) and 2 years (RADIANCE); whole BVL, 31% and 26%; thalamic volume loss, 32% and 27%; and cortical grey matter volume loss, 84% and 60%, respectively.2,3
Adverse Events Reported in the ENLIGHTEN Trial in Patients With Early RMS at 1 Year of Treatment4

Chart depicting the incidence of adverse events at Year 1 Chart depicting the incidence of adverse events at Year 1
Chart depicting the incidence of adverse events at Year 1 Chart depicting the incidence of adverse events at Year 1

The safety profile for patients with early RMS is generally similar to
TEAEs observed in
pivotal trials2-4

Discontinuation rate
due to AEs
1.6%2-4*

*Discontinuation rates due to AEs in
pivotal trials were:
  • In SUNBEAM: 2.9% for ZEPOSIA and
    3.6% for Avonex
  • In RADIANCE: 3.0% for ZEPOSIA and
    4.1% for Avonex
dPandemic began at start of trial.
ZEPOSIA pivotal trials SUNBEAM (1 year; N=1346) and RADIANCE (2 years; N=1313) adverse reactions: Overall incidence of adverse reactions for ZEPOSIA vs Avonex at 1 year was 59.8% and 75.5%, respectively, and at 2 years was 74.7% and 83.0%, respectively. Across 2 head-to-head trials, the most common adverse reactions with an incidence of at least 2% in patients treated with ZEPOSIA and at least 1% greater than Avonex, respectively, were as follows: upper respiratory infection, 26% (vs 23%); hepatic transaminase elevation, 10% (vs 5%); orthostatic hypotension, 4% (vs 3%); urinary tract infection, 4% (vs 3%); back pain, 4% (vs 3%); hypertension, 4% (vs 2%); and upper abdominal pain, 2% (vs 1%). Data are not an adequate basis for comparison of rates between ZEPOSIA and the active control. Upper respiratory infection includes nasopharyngitis, upper respiratory tract infection, pharyngitis, respiratory tract infection, bronchitis, rhinitis, viral respiratory tract infection, viral upper respiratory tract infection, rhinorrhea, tracheitis, and laryngitis. Hepatic transaminase elevation includes alanine aminotransferase increased, gamma-glutamyl transferase increased, aspartate aminotransferase increased, hepatic enzyme increased, liver function test abnormal, and transaminase increased. Hypertension includes hypertension, essential hypertension, and orthostatic hypertension. Severe adverse reactions: the rate of severe adverse reactions at 1 year for ZEPOSIA was 1.6% vs 2.2% for Avonex and the rate at 2 years for ZEPOSIA was 3.5% vs 4.3% for Avonex. Serious adverse reactions: the rate of serious adverse reactions at 1 year for ZEPOSIA was 2.9% vs 2.5% for Avonex and the rate at 2 years for ZEPOSIA was 6.5% vs 6.4% for Avonex. Please see the full Prescribing Information for additional SUNBEAM and RADIANCE data.1-3,10
AE=adverse event.
Explore the efficacy data
Explore the safety profile

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