FREEDOMS Fact Sheet

What is FREEDOMS? • FREEDOMS ( Fingolimod Research Evaluating Effects of Daily Oral treatment in Multiple Sclerosis) is a two year, double-blind, placebo controlled study designed to assess the efficacy, safety and tolerability of FTY720 in patients with relapsing-remitting multiple sclerosis (RRMS), the most common form of MS. • FREEDOMS is part of the FTY720 (fingolimod) phase III study program. • The FREEDOMS study was published in the New England Journal of Medicine (NEJM) issue of February 4th , 2010 1.

What is the study design? • 1,272 patients with RRMS were randomized to receive treatment with FTY720 0.5 mg, FTY720 1.25 mg or placebo once daily for up to two years.

FREEDOMS Study Design

What was the primary endpoint? • The primary aim of the study was to assess the superiority of FTY720 over placebo as assessed by annualized relapse rate (ARR).

What were the key secondary endpoints? • To evaluate the effect of FTY720 on time to disability progression, as measured by the Expanded Disability Status Scale (EDSS) score compared to placebo. • To evaluate the safety and tolerability of FTY720 compared to placebo.

What were the inclusion criteria for enrolment? • Men or women aged 18–55 years. • Diagnosis of MS according to the 2005 revised McDonald criteria *with a relapsing–remitting disease course: • ≥ One documented relapse during the preceding year or • ≥ Two documented relapses within the preceding two years. • EDSS score 0–5.5. • Neurologically stable with no evidence of relapse within 30 days prior to randomization.

* The McDonald criteria are diagnostic criteria for MS, which use both clinical presentation (number of MS attacks) and magnetic resonance imaging techniques (to detect brain lesions) to diagnose MS.

Where was the study conducted? • FREEDOMS was conducted in 22 countries worldwide: Australia, Belgium, Canada, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, The Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Sweden, Switzerland, Turkey and the UK.

What patient population was studied? • A total of 1,272 patients (70% female) with a mean age of 37 years were randomized to treatment. • At baseline, the mean MS duration from first symptoms was 8.2 years. • At baseline, the mean number of relapses was 1.5 within the past year and 2.1 within the past 2 years. † • At baseline, the mean EDSS score was 2.4. • Approximately 59% of patients entering the study had received no previous treatment for MS, and 41% had received disease-modifying treatment for MS at some point prior to entering the study.

What happened with the patients after the study? • Patients in FREEDOMS were offered to continue on FTY720 in the long-term extension study. • All patients in the extension study are receiving FTY720 and all patients previously receiving the 1.25 mg dose are being switched to the 0.5 mg dose.

Kurtzke Expanded Disability Status Scale (EDSS) † The EDSS is a method of quantifying disability in MS. It quantifies disability in eight Functional Systems (FS):

• Pyramidal (limb movement) • Cerebellar (coordination) • Brain stem (speech and swallowing) • Sensory (touch and pain) • Bowel and bladder functions • Visual • Mental • Other (includes any other neurological findings due to MS)

A score of 0 represents no disability; EDSS steps 1.0 to 4.5 refer to people with MS who are fully ambulatory. EDSS steps 5.0 to 9.5 are defined by the impairment to walking – for example a score of 5.5 is defined as ‘disability severe enough to preclude full daily activities. Able to walk without aid or rest for 100m’. A score of 9.5 is ‘confined to bed and totally dependent. Unable to communicated effectively or eat/swallow’.

Reference: 1. Kappos L, et al. Placebo-Controlled Study of Oral Fingolimod in Relapsing Multiple Sclerosis. N Eng J Med . Vol.362 No.5, Feb 4, 2010.

† A to Z of MS Expanded Disability Status Scale (EDSS). Multiple Sclerosis Trust (www.mstrust.org.uk/atoz/edss.jsp). Last accessed Jan 2010.