Inclusion Criteria:

Patients eligible for inclusion in this Treatment Plan have to meet all of the following
criteria:

1. Adult patients who are able to provide written informed consent and have done so
Note: proof of efficacy in the Phase III EXPAND study (Kappos et al 2018) has been
obtained in patients who were aged 18 to 61 years (inclusive) at screening

2. Diagnosis of SPMS with active disease. The SPMS diagnosis must follow an initial
relapsing-remitting disease course of multiple sclerosis (MS) and align with the
diagnostic criteria published (Lublin and Reingold 1996, Rovaris et al 2006, Lublin
et al 2014)

3. Patient is ambulatory, i.e., has an EDSS score of ≤6.5

4. Patient has no comparable or satisfactory alternative therapy available for
treatment of SPMS Written patient informed consent must be obtained prior to start
of treatment. If consent cannot be expressed in writing, it must be formally
documented and witnessed, ideally via an independent trusted witness.

Exclusion Criteria:

Patients eligible for this Treatment Plan must not meet any of the following criteria:

1. Disease exclusions

1. Relapsing-remitting multiple sclerosis

2. Primary progressive multiple sclerosis

3. Secondary progressive multiple sclerosis without active disease

2. Medical conditions precluding inclusion such as lab abnormalities or underlying
diseases

1. Patients with an active or stable but treated chronic disease of the immune
system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjogren's
syndrome, Crohn's disease, ulcerative colitis, etc.) or with a known
immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug-induced
immune deficiency)

2. Severe active infections Patients affected by severe infections should only be
included after full resolution of the condition

3. Second-degree AV block Mobitz type II or higher, sick-sinus syndrome,
sino-atrial heart block or significant QT prolongation (QTc ≥500 msec).

4. History of cardiac arrest, recurrent syncope, symptomatic bradycardia, severe
cerebrovascular disease, uncontrolled hypertension or severe untreated sleep
apnea.

5. Significant liver disease

6. Ongoing macular edema (patients with a history of resolved macular edema are
allowed to enter the program)

7. Patients homozygous for CYP2C9*3 (CYP2C9*3*3 genotype)

8. Patients without a health-care professional confirmed history of chickenpox or
documentation of a full course of vaccination with varicella vaccine. They have
to undergo antibody testing to varicella zoster virus (VZV) before initiating
treatment with siponimod. A full course of vaccination for antibody-negative
patients with varicella vaccine is required prior to commencing treatment with
siponimod. Initiation of treatment with siponimod has be postponed for one
month after completion of the vaccination course to allow full effect of
vaccination to occur.

9. History of hypersensitivity to any drugs or metabolites of similar chemical
classes as siponimod.

3. Prior therapy precluding enrollment:

1. Natalizumab, immunosuppressive/chemotherapeutic medications (e.g. azathioprine,
methotrexate) within 6 months prior to enrollment

2. Rituximab, ofatumumab, ocrelizumab, cladribine, or cyclophosphamide within one
year prior to enrollment

3. Any mitoxantrone during previous two years prior to enrollment or evidence of
cardiotoxicity following mitoxantrone or a cumulative life-time dose of more
than 60 mg/m2

4. alemtuzumab, lymphoid irradiation, bone marrow transplantation or other
immunosuppressive treatments with effects potentially lasting over 6 months, at
any time

4. Concomitant therapy precluding enrollment:

1. Alemtuzumab, azathioprine, cyclophosphamide, cyclosporine, methotrexate,
mitoxantrone, natalizumab, rituximab, ofatumumab, or ocrelizumab as
immunosuppressive or immune-modulating therapies

2. Only during treatment initiation: Class Ia (e.g. quinidine, procainamide),
Class III anti-arrhythmic drugs (e.g. amiodarone, sotalol) during treatment
initiation

5. Have any of the following out-of-range laboratory values:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or
gamma-glutamyl transferase (GGT) greater than 5 times the upper limit of normal
(ULN) range

2. White blood cell (WBC) count < 3,500/mm3 (< 3.5 x 109/L)

3. Lymphocyte count < 800/mm3 (< 0.8 x 109/L)

4. Serum potassium > ULN

6. Participation in a prior investigational study within 30 days prior to enrollment or
within five half-lives of the investigational study drug or until the expected
pharmacodynamic effect has returned to baseline, whichever is longer

7. Pregnancy statements and contraception requirements

1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state
of a female after conception and until the termination of gestation, confirmed
by a positive hCG laboratory test (> 5 mIU/mL).

2. Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, UNLESS they are:

- Women whose partners have been sterilized by vasectomy or other means.

- Using a highly effective method of birth control for the duration of
treatment with siponimod and for at least ten days after stopping
treatment with siponimod. Highly effective method of birth control are
such resulting in a less than 1% per year failure rate when used
consistently and correctly, such as implants, injectables, combined oral
contraceptives, and some intrauterine devices (IUDs); periodic abstinence
(e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not
acceptable.

- Total abstinence from female-male intercourse (when this is in line with
the preferred and usual lifestyle of the subject, if accepted by local
regulation)

8. Not able to understand and to comply with treatment instructions and requirements.