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Promising Multiple Sclerosis Agents In Late-Stage Development
Multiple sclerosis (MS) is a chronic neurodegenerative condition that is estimated to affect over 400,000 individuals in the United States.1 The pathology of MS is complex and involves chronic inflammation within the patient’s central nervous system (CNS) resulting in demyelination of neurons, which leads to various disabilities. These disabilities can present as weakness, difficulty swallowing, tremors, impaired bowel or bladder function, numbness, or visual changes. Based upon the presentation and progression of MS, patients with the condition can generally be subdivided into having primary-progressive MS (PPMS), in which patients experience a continuous progression of disability without episodes of remission or relapse, or relapsing MS (RMS), in which patients present with distinct episodes of disability lasting for days to weeks but make either a full or a partial recovery. Secondary-progressive MS (SPMS) is seen in patients with RMS when their disease becomes continuously progressive and they experience more frequent attacks and an accumulation of disability.2 Common methods used to characterize the disease include the presence of gadolinium-enhancing lesions (GdE) in the brain, or scoring systems such as the Expanded Disability Status Scale (EDSS), which uses a scale of 1–10 to rate a patient’s disease ranging from no disability to death due to MS.3
Current management of MS involves a variety of medications that focus on inhibiting inflammation and blunting the immune system through different mechanisms. There are a number of limitations with currently available therapies ranging from routes of medication administration to serious adverse effects, making the need for new therapies highly desirable. A summary of medications approved for the treatment of MS is provided in
Several areas serve as opportunities for improvement in patient care. The development of an overall cure for MS or effective therapies for patients with PPMS presents a huge challenge to researchers and clinicians. The development of medications with improved safety profiles and the need to increase the affordability of treatment are also key concerns.5 The pipeline for MS is robust, as pharmaceutical companies are aiming to meet these needs with many agents in various stages of development. In no particular order, this review will highlight agents in late-stage development, with a full listing of reviewed medications provided in
Ofatumumab (Arzerra, Novartis) is a fully humanized monoclonal antibody that targets the CD20 receptor of B cells and is currently approved for the treatment of chronic lymphocytic leukemia. 6 After binding to the cell surface, ofatumumab induces B-cell lysis, likely through complement-dependent cytotoxicity or through antibody-dependent, cell-mediated cytotoxicity.6 Through the depletion of circulating B cells, ofatumumab is thought to reduce both inflammation in the CNS and further neuronal damage.
A phase 2 dose-finding study (MIRROR) evaluated three doses (3 mg, 30 mg, and 60 mg) administered as subcutaneous injections every 4–12 weeks in patients with RMS. A total of 232 patients were randomized and 214 completed treatment through 24 weeks. Between weeks 0 and 12, a 65% reduction (rate ratio, 0.35; 95% CI, 0.221–0.548; P < 0.001) in the mean rate of cumulative new GdE lesions was seen for all ofatumumab groups. A > 90% reduction in new GdE lesions was noted for patients receiving > 30 mg every 12 weeks. Regarding safety, 64% of placebo patients and 74% of ofatumumab patients experienced an adverse effect. Most adverse effects were labeled as mild to moderate, with injection-related reactions being the most frequently reported among patients (41–66% of ofatumumab patients vs. 15% of placebo patients).7 Based on these results, a dose of 20 mg given every four weeks as a subcutaneous injection was chosen for evaluation in phase 3 trials.8
ASCLEPIOS I and II, two ongoing phase 3 trials, are comparing the efficacy of ofatumumab against teriflunomide (Aubagio, Sanofi) in patients with RMS. Both trials aim to enroll 900 participants between the ages of 18 and 55 with an EDSS score of 0–5.5, who have had one relapse within the past year or two relapses in the previous two years. The primary outcomes of both trials will be a reduction in the annualized relapse rate (ARR), while secondary endpoints include three- and six-month changes in the EDSS score as well as observed changes in GdE or T2 lesions on magnetic resonance imaging (MRI) scans. The anticipated completion date for both trials is May 2019.9,10 Ofatumumab will be the second CD20-targeting monoclonal antibody to be used in MS treatment and will need to differentiate itself from ocrelizumab (Ocrevus, Genentech), which has been on the market since 2017. A key difference will be the dosing routes and frequency; ocrelizumab is administered as an intravenous infusion every six months whereas ofatumumab is a monthly subcutaneous injection that can be administered by the patient.
Ublituximab (TG Therapeutics) is a chimeric monoclonal antibody that also targets the CD20 receptor, and it is being evaluated for use in RMS. Compared to other CD20 monoclonal antibodies, ublituximab is glycoengineered to increase its interactions with the FcγRIIIa (CD16) receptor, which enhances its ability to produce antibody-dependent cellular cytotoxicity.11
In a phase 2 dose-finding study, 48 patients were enrolled and received an initial 150-mg infusion over four hours, followed two weeks later by a 450-mg infusion over three hours. A third infusion at week 24 of either 450 mg or 600 mg infused over one hour was also administered. Within four weeks, there was an observed median 99% depletion of B cells, which was maintained at week 24. At week 24, it was also observed that the number of T1 GdE lesions had decreased to zero in all subjects (n = 44) from a baseline of 3.8 lesions (P = 0.003), and this was maintained at week 48 in 14 observable patients. The most commonly reported adverse effects were infusion-related reactions, fatigue, and headache, but these and other observed effects were mostly mild.12 Two ongoing phase 3 trials (ULTIMATE I and II) are evaluating the impact of ublituximab on the ARR over the course of 96 weeks compared to that of teriflunomide. Both of these trials aim to enroll 440 patients aged 18 to 55 years with active disease and an EDSS score of 0–5.5, and they have an estimated completion date of late 2021.13,14
Siponimod, Ozanimod, and Ponesimod
Siponimod, ozanimod, and ponesimod are three upcoming, second-generation S1P-receptor modulators. Fingolimod (Gilenya, Novartis), the first agent approved in this class, is associated with serious adverse effects involving the cardiovascular system, such as bradycardia and reduction in atrioventricular (AV) conduction, and effects involving the immune system, such as lymphopenia and leukopenia, which may result in potentially serious infections.15 Although fingolimod is a non-selective inhibitor of the S1P-receptor family, these newer agents are more selective, which developers believe will translate into enhanced efficacy and safety.5 As a class, they work by inhibiting the migration of lymphocytes into the CNS.
Siponimod (Novartis) is an SP1-receptor modulator that targets the S1P1 and S1P5 receptor subtypes. A positive phase 2, placebo-controlled trial (BOLD) recruited 297 patients with RRMS to receive either 0.25 mg, 0.5 mg, 1.25 mg, 2 mg, or 10 mg orally daily or placebo daily for three to six months. There was a positive correlation with increasing doses and reductions in combined, unique active lesions. Compared to placebo, the 0.25-mg, 0.5-mg, 1.25-mg, 2-mg, and 10-mg doses resulted in a 44.3%, 61.5%, 86.1%, 69.7%, and 74.3% relative reduction in lesions, respectively. The frequency of experiencing any adverse effect ranged from 74% to 96% in patients receiving siponimod, compared to 6 to 9% of placebo patients. Patients receiving the 10-mg dose experienced the highest frequency of adverse effects, and overall, 20% of patients had to discontinue therapy because of an adverse effect. The most frequently observed adverse reactions included headache, bradycardia, dizziness, nasopharyngitis, fatigue, nausea, and lymphopenia. Among the adverse cardiac reactions resulting in medication discontinuation, second-degree AV block (four patients), myocardial infarction 45 days after treatment discontinuation (one patient), and bradycardia (one patient) were observed.16
A phase 3 trial evaluating the safety and efficacy of siponimod in 1,652 patients with SPMS is ongoing, with an anticipated completion date sometime in 2023. The primary endpoint is delay in time to confirmed disability-progression, defined as a 1-point increase in EDSS score in patients with a baseline of 3 to 5, or a 0.5-point increase for those with a baseline score of 5.5 to 6.5.17
Ozanimod (Celgene) is another selective oral immunomodulator selectively targeting the S1P1 and S1P5 receptors. Two phase 3 clinical trials (RADIANCE Part B and SUNBEAM) have reported on the safety and efficacy of ozanimod for up to two years in patients with RMS. Both trials evaluated either 0.5 mg or 1 mg orally, administered daily, against interferon-beta-1a (Avonex, Biogen), with the primary outcome being a reduction in ARR and secondary outcomes focusing on a reduction in T2 or GdE lesions in the brain. In SUNBEAM, 1,346 patients received an average of 13.6 months of treatment, and an ARR of 0.24 (P = 0.0013) and 0.18 (P < 0.0001) was observed in the 0.5-mg and 1-mg groups, respectively, compared to an ARR of 0.35 with interferon-beta-1a. Significant reductions in brain lesions, 25–48% for T2 lesions and 34–63% for GdE, were seen with both doses of ozanimod. Safety results suggest that ozanimod is well tolerated, with nasopharyngitis, headache, and upper respiratory tract infections being most commonly reported, along with transient increases in alanine aminotransferase. Serious adverse effects rates were 2.9–3.5% with ozanimod versus 2.5% for interferon-beta-1a, with no reports of AV block.18 Results from RADIANCE Part B showed similar rates of ARR with 0.17 (P < 0.0001) and 0.22 (P = 0.0032) for 1 mg and 0.5 mg, respectively, compared to 0.28 for interferon-beta-1a. A 32–42% reduction in T2 weighted lesions and a 47–53% reduction in GdE lesions were also reported.19 Detailed safety data were not available but preliminary releases cited rates of serious adverse effects in 6.5% to 7.1% of ozanimod patients and in 6.4% of interferon-beta-1a patients, and a slightly higher rate of therapy discontinuation in the interferon-beta-1a arm compared to the ozanimod arm, at 4.1% versus 3–3.2%, respectively. No reports of second-degree or higher AV block were seen following the initial dose.20
Ponesimod (Actelion) is another S1P-receptor modulator in development. It differs from ozanimod and siponimod due to its high selectivity for only the S1P1-receptor subtype. The phase 2b clinical trial evaluated once-daily doses of 10 mg, 20 mg, and 40 mg of ponesimod against placebo in 464 patients with RMS. The primary endpoint was the number of new GdE lesions on T1-weighted MRIs. Patients receiving placebo were observed to have 6.2 new lesions at 24 weeks compared to 3.5, 1.1, and 1.4 new lesions in the 10-mg, 20-mg, and 40-mg ponesimod groups, respectively. ARR at week 24 was 0.525 with placebo and 0.332, 0.417, and 0.251 with ponesimod 10 mg, 20 mg, and 40 mg, respectively. Nine patients receiving ponesimod discontinued treatment due to cardiac adverse effects, with most experiencing onset with their first dose. In addition, respiratory adverse effects including dyspnea, and decreases in Forced Expiratory Volume over one second (FEV1) were observed in a dose-dependent manner in patients receiving ponesimod.21
Ponesimod is undergoing phase 3 evaluation against teriflunomide in patients with RMS. The OPTIMUM trial is aiming to enroll 1,100 patients to receive daily doses of either ponesimod 20 mg or teriflunomide 14 mg, with a primary outcome of reduction in ARR over 108 weeks. Secondary endpoints include 12-week confirmed disability accumulation, percent changes in brain volume, time to first relapse, cumulative number of combined, unique active brain lesions, and changes in fatigue-related symptoms. The estimated date for trial completion is May 2019.22
Masitinib (Masivet, AB Science) is a novel oral therapy and represents a first-in-class tyrosine kinase inhibitor (TKI) aimed at treating patients with PPMS and relapse-free secondary progressive MS (rfSPMS). Unlike other TKIs, masitinib is highly selective for inhibiting the KIT receptor, which has a role in promoting cell growth, differentiation, and migration while not inhibiting other kinases associated with adverse effects, such as cardiotoxicity.23
Data from a small phase 2 pilot study with 35 patients with PPMS or rfSPMS showed a benefit with masitinib when compared to placebo, as demonstrated by an increase in patients’ multiple sclerosis functional composite (MSFC) score (+103% + 189 vs. −60% + 190) at 12 months. Also, EDSS scores remained stable for patients receiving masitinib. The most frequently observed adverse reactions included asthenia (41%), rash (26%), nausea (22%), edema (19%), and diarrhea (11%), along with laboratory abnormalities such as leucopenia (22%) and lymphopenia (15%). The majority of adverse reactions were mild to moderate in intensity.24 An ongoing phase 3 trial aims to enroll 450 patients with PPMS or rfSPMS to receive either placebo or masitinib 6 mg/kg daily. Patients with an EDSS score of two to six who have had a score progression of > 1 point within the previous two years are eligible for inclusion. The primary outcome will be focusing on EDSS score changes at 96 weeks, and the anticipated trial completion date is July 2019.25
MD1003 (MedDay Pharmaceuticals), a novel oral medication containing a highly concentrated form of biotin, is being investigated in the treatment of patients with SPMS and PPMS. Biotin is known to be involved in many pathways that modulate energy production, neural growth, and myelin production, and supplementation is thought to help promote the repair and prevention of axon degeneration. This formulation targets patients with non-active forms of progressive MS who are not exhibiting CNS inflammation.5
A phase 3, double-blind, placebo-controlled trial compared MD1003 to placebo in 154 patients with a baseline EDSS score of 4.5–7 and evidence of disease progression within the previous two years. Patients were randomized to receive MD1003 or placebo three times a day for 12 months, at which point the patients receiving placebo were eligible to receive MD1003 in an open-label extension of the study. At 12 months, 13 (12.6%) of the patients receiving MD1003 had an observed reduction in MS-related disability compared to no patients in the placebo group (P = 0.005), as evidenced by improved EDSS scores or improved 25-foot walk times (TW25). Disease progression at 12 months was observed in 13.6% of placebo patients and in 4.2% of MD1003 patients (P = 0.07). Following the open-label extension, observations at 18 months showed 31.7% of patients who initially received placebo exhibiting disease progression, compared to 9.9% of patients who continuously received MD1003 (P = 0.005). Rates of adverse effects were similar between MD1003 and placebo, with most being reported as mild to moderate. Serious adverse effects included MS relapse (4.9% in MD1003 patients and 7.8% in placebo patients), development of a mucocutaneous rash in one patient receiving MD1003, and hyperthyroidism in six patients receiving MD1003 during the placebo phase and five additional cases during the open-label extension. Development of new MS-specific brain lesions was seen in 23.4% of MD1003 patients compared to 13% of placebo patients (P = 0.36) during the trial’s blinded phase.26 An ongoing phase 3 trial aims to enroll 600 patients with progressive MS and will randomize them to receive MD1003 or placebo for 15 to 27 months. Participants will be assessed by changes in their EDSS score and their TW25, with the anticipated completion date being September 2019.27
In the coming years, available treatment options for patients with MS are expected to expand. The addition of several next-generation agents seeking to improve upon already utilized medication classes, and novel agents targeting new pathways, will provide practitioners with more options and, perhaps, create competition to increase treatment affordability. While initial results from phase 2 trials seem promising, efficacy and safety data from phase 3 studies will be anticipated before determining where future agents fit within treatment algorithms.
Current FDA-Approved Medications for Multiple Sclerosis
|Medication||Indications||Formulations||General Maintenance Dosing||Estimated Price Per Dose
|Interferon-beta-1a (Avonex, Rebif, Plegridy)||RMS||
|Interferon-beta-1b (Betaseron, Extavia)||RMS||SQ injection||250 mcg (8 million IU) every other day||$504–$533 per dose (depending on brand)||None|
|Glatiramer acetate (Copaxone, Glatopa)||RMS||SQ injection||
|Mitoxantrone (Novantrone)||SPMS, PRMS, worsening RMS||IV infusion||12 mg/m2 every three months||$255 per 25-mg dose||Yes|
|Natalizumab (Tysabri)||RMS||IV infusion||300 mg every four weeks||$7,416 per 300-mg infusion||None|
|Alemtuzumab (Lemtrada)||RMS||IV infusion||12 mg/day for 5 days; 12 mg/day for 3 days for 12 months after||$26,814 per 12-mg infusion||None|
|Fingolimod (Gilenya)||RMS||Oral capsule||0.5 mg once daily||$314 per 0.5-mg capsule||None|
|Teriflunomide (Aubagio)||RMS||Oral tablet||7 mg once daily||$279 per 7-mg tablet||None|
|Dimethyl fumarate (Tecfidera)||RMS||Delayed release, oral capsule||240 mg twice daily||$147 per 240-mg capsule||None|
*Pricing based on listed Average Wholesale Price (AWP).
IM = intramuscular; IU = international unit; IV = intravenous; PRMS = progressive relapsing multiple sclerosis; RMS = relapsing multiple sclerosis; SPMS = secondary-progressive multiple sclerosis; SQ = subcutaneous.
Therapies for Multiple Sclerosis Currently in Late-Stage Development
||Mechanism of Action||Targeted Indication / Population||Route and Dose||Expected Price Strategy||Anticipated Launch Date(s)|
||mAb targeting CD20||Second-line treatment for patients with RMS who relapse on initial therapies or those with highly aggressive disease||30–60 mg subcutaneously every 4 to 12 weeks||10% premium to Ocrevus (ocrelizumab)||United States: 2020|
||mAb targeting CD20||Patients with RMS||450 mg via intravenous infusion on specified days||Priced in line with Ocrevus (ocrelizumab)||United States: 2022|
||S1P receptor modulator||First-line treatment for SPMS||2 mg orally daily||Priced similarly to Gilenya (fingolimod)||United States: 2019|
||S1P receptor modulator||First-line treatment for RMS||0.5 mg or 1 mg orally daily||Priced in line with Gilenya (fingolimod)||United States: 2019|
||S1P receptor modulator||First-line treatment for RMS and SPMS||20 mg orally daily||Priced at small discount to Gilenya (fingolimod)||United States: 2020|
||Tyrosine kinase inhibitor||First-line treatment for PPMS or rfSPMS||6 mg/kg orally daily||Unclear; will depend on initial price set if/when approved for other indications||United States: 2020|
||Promotes neuronal growth and repair in non-inflammatory disease||Not active forms of PPMS and SPMS||100 mg 3 times daily||Priced at 10% discount to Ocrevus (ocrelizumab)||United States: 2020|
ACOT = Annual Cost of Therapy; mAb = monoclonal antibody; 5EU = France, Germany, Italy, Spain, United Kingdom; PPMS = primary-progressive multiple sclerosis; rfSPMS = relapse-free secondary-progressive multiple sclerosis; RMS = relapsing multiple sclerosis; SPMS = secondary-progressive multiple sclerosis.
- Kilokthornsakul P, Valuck RJ, Nair KV, Corboy JR, Allen RR, Campbell JD. Multiple sclerosis prevalence in the United States commercially insured population. Neurology 2016;86:1014–1021.
- Multiple Sclerosis Foundation. What are the different types of MS? July 2018; Available at: https://msfocus.org/Get-Educated/Common-Questions/What-are-the-different-types-of-MS.aspx. Accessed November 5, 2018
- Multiple Sclerosis Trust. Expanded disability status scale (EDSS) February 2018; Available at: https://www.mstrust.org.uk/a-z/expanded-disability-status-scale-edss. Accessed November 5, 2018
- Red Book Online Ann Arbor, Michigan: Truven Health Analytics. Available at: www.micromedexsolutions.com. Accessed November 5, 2018
- GlobalData. Pharmapoint: Multiple sclerosis—Global drug forecast and market analysis to 2026 December 2017; Available at: https://store.globaldata.com/report/gdhc155pidr--pharmapoint-multiple-sclerosis-global-drug-forecast-and-market-analysis-to-2026/. Accessed November 5, 2018
- Arzerra (ofatumumab) prescribing information East Hanover, New Jersey: Novartis Pharmaceuticals Corporation. August 2016;
- Bar-Or A, Grove RA, Austin DJ, et al. Subcutaneous ofatumumab in patients with relapsing–remitting multiple sclerosis: The MIRROR study [published online April 25, 2018]. Neurology 2018;90;(20):e1805–e1814.
- Hauser SL, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in relapsing MS: Adaptive design of two phase 3 studies (ASCLEPIOS I and ASCLEPIOS II). Neurology 2017;88;(16):S16
- ClinicalTrials.gov. Efficacy and safety of ofatumumab compared to teriflunomide in patients with relapsing multiple sclerosis (ASCLEPIOS I) October 4, 2018; Available at: https://clinicaltrials.gov/ct2/show/NCT02792218?term=ofatumumab&cond=Multiple+Sclerosis&rank=2. Accessed: November 5, 2018
- ClinicalTrials.gov. Efficacy and safety of ofatumumab compared to teriflunomide in patients with relapsing multiple sclerosis (ASCLEPIOS II) Updated: September 11, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02792231?term=ofatumumab&cond=Multiple+Sclerosis&rank=6. Accessed: November 5, 2018
- Le Garff-Tavernier M, Decocq J, de Romeuf C, et al. Analysis of CD16+CD56dim NK cells from CLL patients: Evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies [published online October 26, 2010]. Leukemia 2011;25;(1):101–109.
10.1038/leu.2010.240 Fox EJ, Lovett-Racke A, Inglese M, et al. Phase 2 multicenter study results of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody in patients with relapsing forms of multiple sclerosis. Presentation at European Academy of Neurology Annual Congress Lisbon, Portugal June 16–19, 2018
- ClinicalTrials.gov. A phase 3, randomized, multi-center, double-blinded, active-controlled study to assess the efficacy and safety/tolerability of ublituximab as compared to teriflunomide in subjects with relapsing multiple sclerosis (ULTIMATE 1) March 1, 2018; Available at: https://clinicaltrials.gov/ct2/show/NCT03277261?term=Ublituximab&cond=Multiple+Sclerosis&rank=2. Accessed November 5, 2018
- ClinicalTrials.gov. A phase 3, randomized, multi-center, double-blinded, active-controlled study to assess the efficacy and safety/tolerability of ublituximab as compared to teriflunomide in subjects with relapsing multiple sclerosis (ULTIMATE 2) March 1, 2018; Available at: https://clinicaltrials.gov/ct2/show/NCT03277248?term=Ublituximab&cond=Multiple+Sclerosis&rank=3. Accessed November 5, 2018
- Auricchio F, Scavone C, Cimmaruta D, et al. Drugs approved for the treatment of multiple sclerosis: Review of their safety profile [published online October 12, 2017]. Expert Opin Drug Saf 2017;16;(12):1359–1371.
- Selmaj K, Li DK, Hartung HP, et al. Siponimod for patients with relapsing–remitting multiple sclerosis (BOLD): An adaptive, dose-ranging, randomised, phase 2 study [published online June 11, 2013]. Lancet Neurol 2013;12;(8):756–767.
- ClinicalTrials.gov. Exploring the efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis (EXPAND) June 11, 2018; Available at: https://clinicaltrials.gov/ct2/show/NCT01665144?term=siponimod&cond=Multiple+Sclerosis&rank=2. Accessed November 5, 2018
- Celgene press release.
Efficacy and safety results from first phase III trial of oral ozanimod (SUNBEAM) versus an active comparator in relapsing multiple sclerosis presented at MSParis 2017–7th joint ECTRIMS-ACTRIMS meeting October 27, 2017Available at: http://files.shareholder.com/downloads/AMDA-262QUJ/0x0x961423/64BE58DB-21CC-4EC7-A477-37082A2368B6/CELG_News_2017_10_27_General_Releases.pdf. Accessed November 5, 2018
- Koscielny V. Phase III SUNBEAM and RADIANCE PART B trials for Ozanimod in relapsing multiple sclerosis demonstrate superiority versus interferon-β-1a (Avonex®) in reducing annualized relapse rates and MRI brain lesions. Neurodegener Dis Manag 2018;8;(3):141–142.
- Cree B, Bar-Or A, Comi G, et al. Safety of Ozanimod versus Interferon β-1a in two multicenter, randomized, double-blind, parallel-group, active-controlled, double-dummy phase 3 studies in relapsing multiple sclerosis (SUNBEAM and RADIANCE Part B) (S36.006). Neurol 2018;90;(suppl 15):S36.006
- Olsson T, Boster A, Fernandez O, et al. Oral ponesimod in relapsing–remitting multiple sclerosis: A randomized phase II trial [published online March 21, 2014]. J Neurol Neurosurg Psychiatry 2014;85;(11):1198–1208.
- ClinicalTrials.gov. Oral ponesimod versus teriflunomide in relapsing multiple sclerosis (OPTIMUM) October 10, 2018; Available at: https://clinicaltrials.gov/ct2/show/NCT02425644. Accessed November 5, 2018
- Dubreuil P, Letard S, Ciufolini M, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One 2009;4;(9):e7258
- Vermersch P, Benrabah R, Schmidt N, et al. Masitinib treatment in patients with progressive multiple sclerosis: A randomized pilot study. BMC Neurol 2012;12:36
- ClinicalTrials.gov. A phase 3 study to compare efficacy and safety of masitinib to placebo in the treatment of patients with primary progressive or relapse-free secondary progressive multiple sclerosis April 21, 2017; Available at: https://clinicaltrials.gov/ct2/show/NCT01433497?term=masatinib&cond=multiple+sclerosis&rank=2. Accessed November 5, 2018
- Tourbah A, Lebrun-Frenay C, Edan G, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study [published online September 1, 2016]. Mult Scler 2016;22;(13):1719–1731.
- ClinicalTrials.gov. Effect of MD1003 in progressive multiple sclerosis (SPI2) August 28, 2018; Available at: https://clinicaltrials.gov/ct2/show/NCT02936037?term=MD1003&cond=Multiple+Sclerosis&rank=2. Accessed November 5, 2018