There is no specific curative drug available for the treatment of multiple sclerosis. Fortunately, a large number of disease modifying drugs have been developed. New drug development for the treatment of multiple sclerosis is a hot-area, a large number of disease modifying drugs have been developed in the last 2 decades. Nearly 70 different drugs are now available to deal with this debilitating and disabling disease. The list presented here includes 10 disease modifying drugs approved by the US FDA in the last 10 years, from January 2010 to October 2019. In addition to these, a drug, Ampyra (Dalfampridine) 10 mg tablet has been approved by the US FDA in January 2010 for improvement of walking capacity in multiple sclerosis.

1. NEW DRUGS FOR MULTIPLE SCLEROSIS
APPROVED BY THE US FDA IN LAST 10-YEARS
DR. ASHOK KUMAR BATHAM,
M.B.,B.S., M.D., D.C.R.,
DR. BATHAM’S ON-LINE CLINIC
PHONE: +91 93280 18777
EMAIL: ashokpharmacol@gmail.com

2. DRUGS FOR MULTIPLE SCLEROSIS
• There is no specific curative drug available for the treatment of multiple sclerosis.
• Fortunately, a large number of disease modifying drugs have been developed.
• New drug development for the treatment of multiple sclerosis is a hot-area, a large number
of disease modifying drugs have been developed in the last 2 decades.
• Nearly 70 different drugs are now available to deal with this debilitating and disabling
disease.
• The list presented here includes 10 disease modifying drugs approved by the US FDA in the
last 10 years, from January 2010 to October 2019.
• In addition to these, a drug, Ampyra (Dalfampridine) 10 mg tablet has been approved by the
US FDA in January 2010 for improvement of walking capacity in multiple sclerosis.

3. GILENYA (FINGOLIMOD)
• Gilenya (Fingolimod) was initially approved by the US FDA in 2010 to treat adults with relapsing
form of multiple sclerosis (MS).
• Use of Fingolimod in children10 years of age and older with relapsing form, clinically isolated
syndrome, relapsing-remitting disease, and active secondary progressive disease was approved in
May 2018.
• It was the first oral drug approved for the treatment of multiple sclerosis.
• Fingolimod, the active ingredient of Gilenya, is a sphingosine-1-phosphate receptor modulator,
which sequesters lymphocytes in lymph nodes, preventing them from contributing to an
autoimmune reaction.
• The most common side effects with the use of Gilenya include headache, liver enzyme elevation,
diarrhea, cough, flu, sinusitis, back pain, abdominal pain and pain in extremities. Serious risks
include slowing of the heart rate, especially after the first dose, risk of serious infections, vision
problems, progressive multifocal leukoencephalopathy (PML), and posterior reversible
encephalopathy syndrome.
Source: CenterWatch. FDA Approved Drugs 2010.

4. TERIFLUNOMIDE (AUBAGIO)
• In December 2012, the U.S. Food and Drug Administration (FDA) approved Aubagio
(Teriflunomide) as a new once-daily, oral treatment indicated for patients with relapsing
forms of multiple sclerosis (MS).
• The drug has shown significant efficacy across key measures of MS disease activity, including
reducing relapses, slowing the progression of physical disability, and reducing the number of
brain lesions as detected by Magnetic Resonance Imaging (MRI) studies.
• Aubagio (Teriflunomide) is an immunomodulator with anti-inflammatory properties.
• Teriflunomide is the principal active metabolite of leflunomide, an anti-inflammatory disease
modifying drug used in rheumatoid arthritis.
• The exact mechanism of action of Aubagio (Teriflunomide) is not fully understood, however,
it is considered to cause a reduction in the number of activated lymphocytes in the central
nervous system (CNS).
Source: Sanofi, Genzyme. FDA Approves Genzyme’s AUBAGIO® (teriflunomide), a Once-Daily, Oral Treatment for Relapsing Multiple Sclerosis Wednesday, September 12, 2012. CAMBRIDGE, Mass.

5. TECFIDERA (DIMETHYL FUMARATE)
• Tecfidera capsules (Dimethyl fumarate) was approved by The U.S. Food and Drug Administration, as a first-line
disease-modifying therapy for people with relapsing forms of multiple sclerosis (MS) on March 27, 2013.
• Tecfidera is a new oral formulation of dimethyl fumarate developed by Biogen specifically for the treatment of
multiple sclerosis.
• The FDA’s approval was based largely on results of two large-scale phase III clinical trials of Tecfidera capsules
conducted in people with relapsing-remitting MS. Twice-daily administration of Tecfidera has been shown in clinical
trials to significantly reduce relapses and disease activity on brain and spinal cord imaging studies. In one trial, it
reduced progression of disability.
• Tecfidera appears to inhibit immune cells and molecules, and possibly produce anti-oxidant effects that could be
protective against damage to the brain and spinal cord.
• The most common adverse events reported by people taking Tecfidera during the trials were flushing in up to 40%
and gastrointestinal events (such as diarrhea, nausea, and upper abdominal pain).
Source: FDA Approves Twice a Day Capsules Called Tecfidera (formerly called BG-12) for Relapsing MS. March 27, 2013. Multiple Sclerosis Association.

6. PLEGRIDY (PEGINTERFERON BETA-1A) INJECTION
• Plegridy (Peginterferon beta-1a) injection, for subcutaneous injection, approved by The US FDA on
August 15, 2014, for the treatment of patients with relapsing forms of multiple sclerosis: clinically
isolated syndrome, relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS
with relapses).
• Pegridy is an injectable formulation, administered subcutaneously, once every two weeks.
• Plegridy is an immunomodulator which reduces the bouts of severe inflammatory attacks on the
myelinated neurons of the central nervous system (CNS).
• The US FDA approval of Plegridy in multiple sclerosis was mostly based on a Phase 3 clinical trial in 1,512
patients showing its efficiency and efficacy in reducing the number of relapses, reducing new lesion
growth and progression of disability.
• The most common side effects reported include the appearance of flu-like symptoms, anaphylactic
reactions, muscle pain, itching, fever, seizures, and fatigue. It should be avoided in people with liver
diseases, heart problems, bleeding problems, low blood counts, and mental depression.
Source: National Multiple Sclerosis Society, August 15, 2014.

7. LEMTRADA (ALEMTUZUMAB)
• Lemtrada (alemtuzumab) was approved by the US FDA on November,2019 for the long-term
treatment of relapsing forms of multiple sclerosis (MS), as a second-line therapy.
• Lemtrada is has a unique dosage schedule of intravenous (IV) infusion for a course of five
days, followed one year later by a second three-day course.
• Lemtrada rapidly depletes or suppresses immune system cells (T and B cells) that damage the
myelin sheath of nerves in CNS in MS.
• In clinical trials, Lemtrada was shown to significantly reduce the relapse rate for individuals
with relapsing-remitting MS, as well as significantly reduce the risk of sustained disability
accumulation.
• Adverse events from Lemtrada can include infusion reactions to the medication, increased risk
of infection, and emergent autoimmune diseases.
• Lemtrada is only available through a restricted distribution program, Lemtrada REMS (Risk
Evaluation and Mitigation Strategy).
Source: FDA Approval for Alemtuzumab (Lemtrada) in MS. News > Medscape Medical News > FDA Approvals.Susan Jeffrey. November 15, 2014.

8. ZINBRYTA (DACLIZUMAB)
• Zinbryta is a long-acting injection meant for monthly self-administration by the patient.
• The U.S. Food and Drug Administration approved Zinbryta (Daclizumab), manufactured by Biogen,
Inc. of Cambridge, Massachusetts, for the treatment of adults with relapsing forms of multiple
sclerosis (MS) on May 27, 2016.
• The effectiveness of Zinbryta was shown in two clinical trials in which 1,841 and 412 participants
were studied for 144 and 52 weeks, respectively.
• The drug can cause severe liver injury, and immune conditions, such as non-infectious colitis, skin
reactions, and lymphadenopathy, in addition to hypersensitivity reactions (anaphylaxis or
angioedema), increased risk of infections, and symptoms of depression and/or suicidal ideation.
•
Source: FDA News Release. May 27, 2016.

9. OCREVUS (OCRELIZUMAB)
• Approved by the US FDA on March 28,2019 to treat adult patients with relapsing forms of multiple sclerosis
(MS) and primary progressive multiple sclerosis (PPMS).
• This is the first drug approved by the FDA for PPMS.
• Ocrevus is an intravenous infusion to be given by a health care professional.
• The efficacy of Ocrevus for the treatment of relapsing forms of MS was shown in two clinical trials in 1,656
participants treated for 96 weeks. Both studies compared Ocrevus to another MS drug, Rebif (interferon beta-
1a). In both studies, the patients receiving Ocrevus had reduced relapse rates and reduced worsening of
disability compared to Rebif.
• In a study of PPMS in 732 participants treated for at least 120 weeks, those receiving Ocrevus showed a longer
time to the worsening of disability compared to placebo.
• Ocrevus can cause potentially serious, infusion-related reactions. Additionally, Ocrevus may increase the risk
for malignancies, particularly breast cancer. Patients with active infections are advised to defer treatment
with Ocrevus. Vaccination with live or live attenuated vaccines is not recommended in patients receiving
Ocrevus.
Source: FDA Press Release. FDA approves new drug to treat multiple sclerosis. March 29, 2017.

10. MAVENCLAD (CLADRIBINE)
• The US FDA approved Mavenclad (Cladribine) tablets of Merck in March 2019 for the treatment of relapsing
multiple sclerosis.
• Mavenclad (Cladribine) is a purine antimetabolite, considered to cause impairment of DNA synthesis leading
to cytotoxic effects on B and T lymphocytes resulting in depletion of lymphocytes.
• Mavenclad is specifically indicated for the treatment of relapsing forms of multiple sclerosis (MS), relapsing-
remitting disease, and active secondary progressive disease, in adults.
• The use of Mavenclad is generally recommended for patients who have had an inadequate response to, or are
unable to tolerate, an alternate drug indicated for the treatment of MS.
• The FDA approval of Mavenclad was based on a 96-week randomized, double-blind, placebo-controlled clinical
study in1,326 patients with relapsing forms of MS.
• Adverse effects associated with the use of Mavenclad may include upper respiratory tract infection, headache,
lymphopenia. The drug may increase the risk of malignancy.
Source: CentreWatch. FDA Drug Approvals 2019.

11. MAYZENT (SIPONIMOD) TABLETS
• The US FDA granted approval to Mayzent (Siponimod) tablets in March 2019 for the
treatment of adults with relapsing forms of multiple sclerosis (MS), clinically isolated
syndrome, relapsing-remitting disease, and active secondary progressive disease.
• The efficacy of Mayzent was shown in a clinical trial of 1,651 patients that compared Mayzent
to placebo in patients with secondary progressive multiple sclerosis (SPMS) who had evidence
of disability progression in the prior two years and no relapses in the three months prior to
enrolment.
• The most common adverse reactions in the clinical trials included headache, high blood
pressure and elevations of liver enzymes.
• The drug may cause macular edema, which may necessitate consultation with a physician if
any patient experiences a change in vision.
Source: FDA approves new oral drug to treat multiple sclerosis. Press Release: March 26, 2019.

12. VUMERITY (DIROXIMEL FUMARATE)
• Novel oral fumarate, related to dimethyl fumarate (Tecfidera).
• Approval granted to Biogen Inc. and Alkermes plc by the US FDA on October 30, 2019 for
the treatment of relapsing forms of multiple sclerosis (MS):
• clinically isolated syndrome,
• relapsing-remitting disease and
• active secondary progressive disease.
• The FDA approval was based on data from pharmacokinetic bridging studies comparing
Vumerity and Tecfidera to establish bioequivalence, and reliance on the safety and
efficacy of Tecfidera.
• Vumerity is an improvised form of fumarate with significantly improved gastrointestinal
tolerability and lower discontinuation rate due to g.i. adverse effects (<1 percent vs 6.3
percent).
• Vumerity appears to be a compelling new treatment option for patients.
Source: Globenewswire, October 20,2019.

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