PiPeline Plus
Multiple Sclerosis: Progress, but No Cure Kunj Gohil, PharmD, RPh
M
ultiple sclerosis (MS) is an inflammator y 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 Dr. Gohil is Central Services Manager with Medical Services at MediMedia Managed Markets in Yardley, Pennsylvania.
• 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 • Primar y-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
REFERENCES 1.
2.
3.
4.
National Multiple Sclerosis Society. MS prevalence. Available at: http://www.nationalmssociety.org/About-the-Society/ MS-Prevalence. Accessed August 10, 2015. DiPiro J, Talbert RL, Yee G, et al. Multiple sclerosis. In: Pharmacotherapy: A Pathophysiologic Approach. 9th ed. New York, New York: McGraw-Hill; 2014:835–854. Cleveland Clinic. Multiple sclerosis. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/multiple_sclerosis/ Default.htm. Accessed August 10, 2015. Healthline. Multiple sclerosis: what the future holds. Available at: http://www. healthline.com/health/multiple-sclerosis/what-the-future-holds#1. Accessed August 10, 2015. ■
Future Therapies Drug Status Manufacturer Zinbryta (daclizumab high-yield process) Preregistration Biogen/AbbVie
Regimen Information 150 mg SC daily
Pivotal Studies DECIDE
Expected Approval 2016
Form of MS RRMS
Laquinimod Teva Masitinib AB Science Ocrelizumab Roche Biotin MedDay Tysabri (natalizumab) Biogen Ponesimod Actelion Ozanimod Receptos Siponimod Novartis
Phase 3
0.6 mg PO daily
2015
RRMS
Phase 3
6 mg/kg per day
ALLEGRO, BRAVO, CONCERTO NCT01433497
2016
PPMS, SPMS
Phase 3
600 mg IV every 24 weeks
2016 or later
RMS, PPMS
Phase 3
300 mg PO daily
OPERA, ORATORIO MS-SPI
2016 or later
PPMS, SPMS
Phase 3
300 mg IV every 4 weeks
ASCEND
2016 or later
SPMS
Phase 3
20 mg PO daily
OPTIMUM
2018
RMS
Phase 3
0.5 mg to 1 mg PO daily
2018
RMS
Phase 3
0.25 mg to 2 mg PO daily
RADIANCE, SUNBEAM 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
604 P&T
®
• September 2015 • Vol. 40 No. 9
Pipeline Plus Selected Current Therapiesa Drug Manufacturer Glatopa (glatiramer acetate)e Sandoz
Approval Date 2015
Plegridy (peginterferon beta-1a) Biogen Lemtrada (alemtuzumab) Genzyme Tecfidera (dimethyl fumarate) Biogen Aubagio (teriflunomide) Genzyme Gilenya (fingolimod) Novartis Ampyra (dalfampridine) Acorda Therapeutics Tysabri (natalizumab) Biogen
Relapsing forms of MS
Regimen Informationc 20 mg SC every day
Cost of Course of Therapy per Yeard $78,991
2014
Relapsing forms of MS
125 mcg SC every 14 days
$78,530
2014
Relapsing forms of MS
2013
Relapsing forms of MS
2012
Relapsing forms of MS
7 mg or 14 mg PO daily
$79,438
2010
Relapsing forms of MS
0.5 mg PO daily
$85,136
2010
Improve walking in patients with MS Relapsing forms of MS; severe CD
10 mg PO twice daily
$25,942
300 mg IV every 4 weeks
$82,025
2004
Indicationb
First course: 12 mg/day IV for 5 days; First course: $118,500; second course: 12 mg/day IV for second course: $71,100 3 days, 12 months after first course 240 mg PO twice a day $79,716
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 Avonex (interferon beta-1a) Biogen Copaxone (glatiramer acetate) Teva Betaseron (interferon beta-1b) Bayer
2000
MS; ANLL; advanced PC
12 mg/m2 IV every 3 months
Generic: $718f
1996
Relapsing forms of MS
30 mcg IM once weekly
$78,530
1996
Relapsing forms of MS
20 mg SC daily
$89,213
1993
Relapsing forms of MS
0.25 mg SQ every other day
$54,615
a This list is not all-inclusive; additional therapies may be available for this disease state. b Abbreviated indication provided; for full indication, please refer to prescribing information. c Regimens based on the recommended dosage and maintenance phases from prescribing information; typical doses and titration schedules may vary based on
patient-specific requirements. d Costs calculated using average wholesale price and regimen provided and rounded to the nearest dollar. e Glatopa is the first FDA-approved, substitutable generic version of Copaxone. f 1.9 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
Vol. 40 No. 9 • September 2015 • P&T 605 ®
Multiple Sclerosis: Progress, but No Cure Kunj Gohil, PharmD, RPh
M
ultiple sclerosis (MS) is an inflammator y 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 Dr. Gohil is Central Services Manager with Medical Services at MediMedia Managed Markets in Yardley, Pennsylvania.
• 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 • Primar y-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
REFERENCES 1.
2.
3.
4.
National Multiple Sclerosis Society. MS prevalence. Available at: http://www.nationalmssociety.org/About-the-Society/ MS-Prevalence. Accessed August 10, 2015. DiPiro J, Talbert RL, Yee G, et al. Multiple sclerosis. In: Pharmacotherapy: A Pathophysiologic Approach. 9th ed. New York, New York: McGraw-Hill; 2014:835–854. Cleveland Clinic. Multiple sclerosis. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/multiple_sclerosis/ Default.htm. Accessed August 10, 2015. Healthline. Multiple sclerosis: what the future holds. Available at: http://www. healthline.com/health/multiple-sclerosis/what-the-future-holds#1. Accessed August 10, 2015. ■
Future Therapies Drug Status Manufacturer Zinbryta (daclizumab high-yield process) Preregistration Biogen/AbbVie
Regimen Information 150 mg SC daily
Pivotal Studies DECIDE
Expected Approval 2016
Form of MS RRMS
Laquinimod Teva Masitinib AB Science Ocrelizumab Roche Biotin MedDay Tysabri (natalizumab) Biogen Ponesimod Actelion Ozanimod Receptos Siponimod Novartis
Phase 3
0.6 mg PO daily
2015
RRMS
Phase 3
6 mg/kg per day
ALLEGRO, BRAVO, CONCERTO NCT01433497
2016
PPMS, SPMS
Phase 3
600 mg IV every 24 weeks
2016 or later
RMS, PPMS
Phase 3
300 mg PO daily
OPERA, ORATORIO MS-SPI
2016 or later
PPMS, SPMS
Phase 3
300 mg IV every 4 weeks
ASCEND
2016 or later
SPMS
Phase 3
20 mg PO daily
OPTIMUM
2018
RMS
Phase 3
0.5 mg to 1 mg PO daily
2018
RMS
Phase 3
0.25 mg to 2 mg PO daily
RADIANCE, SUNBEAM 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
604 P&T
®
• September 2015 • Vol. 40 No. 9
Pipeline Plus Selected Current Therapiesa Drug Manufacturer Glatopa (glatiramer acetate)e Sandoz
Approval Date 2015
Plegridy (peginterferon beta-1a) Biogen Lemtrada (alemtuzumab) Genzyme Tecfidera (dimethyl fumarate) Biogen Aubagio (teriflunomide) Genzyme Gilenya (fingolimod) Novartis Ampyra (dalfampridine) Acorda Therapeutics Tysabri (natalizumab) Biogen
Relapsing forms of MS
Regimen Informationc 20 mg SC every day
Cost of Course of Therapy per Yeard $78,991
2014
Relapsing forms of MS
125 mcg SC every 14 days
$78,530
2014
Relapsing forms of MS
2013
Relapsing forms of MS
2012
Relapsing forms of MS
7 mg or 14 mg PO daily
$79,438
2010
Relapsing forms of MS
0.5 mg PO daily
$85,136
2010
Improve walking in patients with MS Relapsing forms of MS; severe CD
10 mg PO twice daily
$25,942
300 mg IV every 4 weeks
$82,025
2004
Indicationb
First course: 12 mg/day IV for 5 days; First course: $118,500; second course: 12 mg/day IV for second course: $71,100 3 days, 12 months after first course 240 mg PO twice a day $79,716
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 Avonex (interferon beta-1a) Biogen Copaxone (glatiramer acetate) Teva Betaseron (interferon beta-1b) Bayer
2000
MS; ANLL; advanced PC
12 mg/m2 IV every 3 months
Generic: $718f
1996
Relapsing forms of MS
30 mcg IM once weekly
$78,530
1996
Relapsing forms of MS
20 mg SC daily
$89,213
1993
Relapsing forms of MS
0.25 mg SQ every other day
$54,615
a This list is not all-inclusive; additional therapies may be available for this disease state. b Abbreviated indication provided; for full indication, please refer to prescribing information. c Regimens based on the recommended dosage and maintenance phases from prescribing information; typical doses and titration schedules may vary based on
patient-specific requirements. d Costs calculated using average wholesale price and regimen provided and rounded to the nearest dollar. e Glatopa is the first FDA-approved, substitutable generic version of Copaxone. f 1.9 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
Vol. 40 No. 9 • September 2015 • P&T 605 ®
