Multiple Sclerosis: Progress, but No Cure

Abstract

Agents are approved to treat exacerbations and symptoms and as disease-modifying therapy. Most therapies in the works would address relapsing forms of the disease.

Multiple sclerosis (MS) is an inflammatory disease that affects approximately 400,000 patients in the United States and 2.3 million around the world.¹ The name is characterized by two key elements: multiple, referring to the numerous affected areas within the central nervous system that produce a wide array of neurological symptoms, and sclerosis, referring to the plaques or sclerosed areas commonly associated with the disease.²

No definitive cause has been identified for MS, and the clinical presentation can vary greatly from patient to patient.^2,3 The clinical course is classified into one of four categories based on attributes such as symptoms, relapses, and progression:

• Relapsing–remitting MS (RRMS) is marked by frequent exacerbations; it is the most common form of MS.^2,3

• Secondary-progressive MS (SPMS) is seen when RRMS patients enter a phase in which attacks and remissions are not easily identifiable.^2,3

• Primary-progressive MS (PPMS) is identified by symptoms and a lack of relapses; it is most commonly diagnosed later in life.^2,3

• Primary-relapsing MS (PRMS) affects the smallest group of patients and is characterized by both progression and relapses.^2,3

No cure exists for MS, but multiple agents are FDA-approved to manage the condition.⁴ Current therapies can be divided into three groups: treatment of exacerbations, disease-modifying therapies, and symptomatic therapies.³ Traditional therapy consisted of interferon treatment, but patients did not like this option because of commonly associated adverse events and inconvenient administration.² Newer therapies, some of them administered orally, have since been discovered with novel mechanisms of action.⁴

As we look to the future, the therapies most commonly under investigation would address relapsing forms of MS. Treatments are becoming more efficacious and convenient for patients. Continued therapeutic advances and identification of the causes of MS will hopefully lead to an eventual cure for this disease.⁴

Future Therapies

Drug Manufacturer	Status	Regimen Information	Pivotal Studies	Expected Approval	Form of MS
Zinbryta (daclizumab high-yield process) Biogen/AbbVie	Preregistration	150 mg SC daily	DECIDE	2016	RRMS
Laquinimod Teva	Phase 3	0.6 mg PO daily	ALLEGRO, BRAVO, CONCERTO	2015	RRMS
Masitinib AB Science	Phase 3	6 mg/kg per day	NCT01433497	2016	PPMS, SPMS
Ocrelizumab Roche	Phase 3	600 mg IV every 24 weeks	OPERA, ORATORIO	2016 or later	RMS, PPMS
Biotin MedDay	Phase 3	300 mg PO daily	MS-SPI	2016 or later	PPMS, SPMS
Tysabri (natalizumab) Biogen	Phase 3	300 mg IV every 4 weeks	ASCEND	2016 or later	SPMS
Ponesimod Actelion	Phase 3	20 mg PO daily	OPTIMUM	2018	RMS
Ozanimod Receptos	Phase 3	0.5 mg to 1 mg PO daily	RADIANCE, SUNBEAM	2018	RMS
Siponimod Novartis	Phase 3	0.25 mg to 2 mg PO daily	EXPAND	2019 or later	SPMS

IV = intravenously; MS = multiple sclerosis; PO = orally; PPMS = primary progressive multiple sclerosis; RMS = relapsing multiple sclerosis; RRMS = relapsing–remitting multiple sclerosis; SC = subcutaneously; SPMS = secondary progressive multiple sclerosis

Sources: FDA; GlobalData; company websites; ClinicalTrials.gov

Selected Current Therapies^a

Drug Manufacturer	Approval Date	Indicationb	Regimen Informationc	Cost of Course of Therapy per Yeard
Glatopa (glatiramer acetate)e Sandoz	2015	Relapsing forms of MS	20 mg SC every day	$78,991
Plegridy (peginterferon beta-1a) Biogen	2014	Relapsing forms of MS	125 mcg SC every 14 days	$78,530
Lemtrada (alemtuzumab) Genzyme	2014	Relapsing forms of MS	First course: 12 mg/day IV for 5 days; second course: 12 mg/day IV for 3 days, 12 months after first course	First course: $118,500; second course: $71,100
Tecfidera (dimethyl fumarate) Biogen	2013	Relapsing forms of MS	240 mg PO twice a day	$79,716
Aubagio (teriflunomide) Genzyme	2012	Relapsing forms of MS	7 mg or 14 mg PO daily	$79,438
Gilenya (fingolimod) Novartis	2010	Relapsing forms of MS	0.5 mg PO daily	$85,136
Ampyra (dalfampridine) Acorda Therapeutics	2010	Improve walking in patients with MS	10 mg PO twice daily	$25,942
Tysabri (natalizumab) Biogen	2004	Relapsing forms of MS; severe CD	300 mg IV every 4 weeks	$82,025
Rebif (interferon beta-1a) EMD Serono	2002	Relapsing forms of MS	22 mcg or 44 mcg SC 3 times a week	$169,531
Mitoxantrone Multiple manufacturers	2000	MS; ANLL; advanced PC	12 mg/m2 IV every 3 months	Generic: $718f
Avonex (interferon beta-1a) Biogen	1996	Relapsing forms of MS	30 mcg IM once weekly	$78,530
Copaxone (glatiramer acetate) Teva	1996	Relapsing forms of MS	20 mg SC daily	$89,213
Betaseron (interferon beta-1b) Bayer	1993	Relapsing forms of MS	0.25 mg SQ every other day	$54,615

^aThis list is not all-inclusive; additional therapies may be available for this disease state.

^bAbbreviated indication provided; for full indication, please refer to prescribing information.

^cRegimens based on the recommended dosage and maintenance phases from prescribing information; typical doses and titration schedules may vary based on patient-specific requirements.

^dCosts calculated using average wholesale price and regimen provided and rounded to the nearest dollar.

^eGlatopa is the first FDA-approved, substitutable generic version of Copaxone.

^f1.9 m² used as body surface of average U.S. male.

Sources: Red Book; Drugs@FDA; and prescribing information for all medications

ANLL = acute nonlymphocytic leukemias; CD = Crohn’s disease; IM = intramuscularly; IV = intravenously; MS = multiple sclerosis; PC = prostate cancer; PO = by mouth; SC = subcutaneously