rate (relapses/year) and MRI measures ofinflammatory disease activity.
Study duration was variable for individual patients (median study duration was 21 months, range 1 day-37 months).
Study 1 randomized 1651 patients to either MAYZENT 2 mg (N = 1105) or placebo (N = 546); 82% of MAYZENTtreatedpatients and 78% of placebo-treated patients completed the study. Median age was 49.0 years, 95% of patientswere white, and 60% female. The median disease duration was 16.0 years, and median EDSS score at baseline was 6.0
(56% of patients had ≥ 6.0 EDSS at baseline); 36% of patients had one or more relapses in the 2 years prior to study entry;22% of those patients with availableimaging had one or more gadolinium-enhancing lesions on their baseline MRI scan;78% of patients had been previously treated with an MS therapy.
Results are presented in Table 4. MAYZENT was superior to placebo in reducing the risk of confirmed disabilityprogression, based on a time-to-event analysis (hazard ratio 0.79, p < 0.0134; see Figure 1). MAYZENT did notsignificantly delay the time to 20% deterioration in the timed 25-foot walk, compared to placebo. Patients treated withMAYZENT had a 55% relative reduction in annualized relapse rate, compared to patients on placebo (nominal p-value <0.0001). The absolute reduction in the annualized relapse rate was 0.089. Although MAYZENT had a significant effect ondisability progression compared to placebo in patients with active SPMS (e.g., SPMS patients with an MS relapse in the 2years prior to the study), the effect of MAYZENT in patients with non-active SPMS was not statistically significant (seeFigure 2).
Table 4 Clinical and MRI Results From Study 1
MAYZENT PLACEBO
Clinical Outcomes
Proportion of patients with confirmed
disability progression1
26% 32%
Relative risk reduction 21% (p = 0.0134)*
Absolute risk Reduction 6%
Proportion of patients with confirmed
worsening in timed 25-foot walk
40% 41%
p = NS
Annualized relapse rate2 0.071 0.160
Relative reduction (%) 55% (p < 0.01)˄
Absolute reduction 0.089
p < 0.01^
MRI Endpoints
Change from baseline in T2 lesion
volume (mm3
) (95% CI)3
184
(54; 314)
879
(712; 1047)
p < 0.01˄
All analyses are based on the full analysis set (FAS), which includes all randomized subjects who took at least one dose of study medication. p-values
are two-sided.
(1) Defined as an increase of 1.0 point or more from the baseline Expanded Disability Status Scale (EDSS) score for patients with baseline score of 5.5or less, or 0.5 or more when the baseline score is greater than 5.5. Progression confirmed at 3 months. Cox proportional hazard model.
(2) Defined as the average number of confirmed relapses per year (estimated from negative binomial regression model for recurrent events).
(3) Adjusted mean averaged over Months 12 and 24.
* Statistically significant.
NS, Not statistically significant.
˄ Nominal p value, not corrected for multiple comparisons.
Figure 1 Time to Confirmed Disability Progression Based on EDSS (Study 1)
Figure 2 Time to Confirmed Disability Progression Based on EDSS (Study 1), Subgroup Analysis
*HR and 95% CI presented are model-based estimates for a range of values of age and EDSS.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
MAYZENT film-coated tablets are supplied as follows:
0.25 mg tablet: Pale red, un |
