Table 2 Clinical and MRI Results of Study 1   GILENYA 0.5 mg N=425 Placebo N=418 p-value
Clinical Endpoints    
Annualized relapse rate (primary endpoint) 0.18  0.40 <0.001
Percentage of patients without relapse 70% 46% <0.001
Hazard ratio‡ of disability progression
(95% CI) 0.70
(0.52, 0.96)  0.02
MRI Endpoint   
Mean (median) numberof new or newly enlarging T2 lesionsover 24 months 2.5(0)  9.8 (5.0) <0.001
Mean (median) number of T1 Gd-enhancing lesions at Month 24 0.2(0)  1.1 (0) <0.001

All analyses of clinical endpoints were intent-to–treat. MRI analysis used eva luable dataset.

‡ Hazard ratio is an estimate of the relative risk of having the event of disability progression on GILENYAas compared to placebo.

Figure 1 Time to 3-month Confirmed Disability Progression – Study 1 (ITT population)

Study 2 was a 1-year randomized, double-blind, double-dummy, active-controlled study in patients with RRMS who had not received any natalizumab in the previous 6 months. Prior therapy with interferon-beta or glatiramer acetate up to the time of randomization was permitted.

Neurological eva luations were performed at screening, every 3 months, and at the time of suspected relapses. MRI eva luations were performed at screening and at month 12. The primary endpoint was the annualized relapse rate.

Median age was 36 years, median disease duration was 5.9 years, and median EDSS score at baseline was 2.0. Patients were randomized to receive GILENYA 0.5 mg (n=431), 1.25 mg (n=426), or interferon beta-1a, 30 micrograms via the intramuscular route (IM) once weekly (n=435) for up to 12 months. Median time on study drug was 365 days on GILENYA 0.5 mg, 354 days on 1.25 mg, and 361 days on interferon beta-1a IM.

The annualized relapse rate was significantly lower in patients treated with GILENYA 0.5 mg than in patients who received interferon beta-1a IM. The key secondary endpoints were number of new and newly enlarging T2 lesions and time to onset of 3-month confirmed disability progression as measured by at least a 1-point increase from baseline in EDSS (0.5 point increase for those with baseline EDSS of 5.5) sustained for 3 months. The number of new and newly enlarging T2 lesions was significantly lower in patients treated with GILENYA than in patients who received interferon beta-1a IM. There was no significant difference in the time to 3-month confirmed disability progression between GILENYA and interferon beta-1a-treated patients at 1 year. The 1.25 mg dose resulted in no additional benefit over the GILENYA 0.5 mg dose. The results for this study are shown in Table 3.

Table 3 Clinical and MRI Results of Study 2   GILENYA 0.5 mg N=429 Interferon beta-1a IM 30 μg N=431 p-value
Clinical Endpoints    
Annualized relapse rate (primary endpoint) 0.16 0.33 <0.001
Percentage of patients without relapse 83% 70% <0.001
Hazard ratio‡ of disability progression
(95% CI) 0.71
(0.42, 1.21)  0.21
MRI Endpoint    
Mean (median) num