Current phase 3 studies investigative novel, preventative approaches.
Multiple sclerosis (MS) is a chronic inflammatory condition that affects the central nervous system (CNS), and it can result in significant disability and death. According to the American Academy of Neurology (AAN), more than 2.3 million people are living with MS worldwide, and disease-modifying therapies (DMTs) are considered the mainstay of therapy to help to reduce the frequency and severity of relapses. However, these medications are also associated with adverse effects ranging from mild to life-threatening. Current phase 3 studies are investigating new ways and novel approaches to prevent MS relapses
Healthcare executives are concerned about the cost, quality, and outcomes of MS drugs, making it a top priority for patient care and expenditures. According to a study published in Neurology, out-of-pocket monthly costs for MS medications increased from approximately $15 to about $309 over 12 years. According to the National Multiple Sclerosis Society, the average median price of MS DMTs in 2013 was less than $60,000 while the price in 2018 was $80,000. Patients with MS also face co-insurance that could be as high as 40%, which translates into a monthly cost of over $2,500 for their DMTs.
Legislation that makes MS medications more affordable is needed to alleviate patient costs. Healthcare professionals can play an important role through an interdisciplinary approach to managing patients with MS and identifying financial options such as patient assistance programs to alleviate costs.
Phase 3 MS drugs in the pipeline
Erin Lopata PharmD, MPH, senior director, Access Experience Team at Precision for Value points out that Tecfidera (dimethyl fumarate) is approaching the end of its patent exclusivity, and there are several similar medications that are anticipated for FDA drug approval. Lopata adds that Vumerity (diroximel fumarate) is a prodrug for monomethyl fumarate, which is the active metabolite of Tecfidera and may cause less gastrointestinal adverse events.
Interim efficacy and safety results from the Phase 3 EVOLVE-MS-1 study were recently presented at the AAN Annual meeting, and showed that after 48 weeks, relapse rates decreased by about 79% relative to baseline. Biogen has submitted the new drug application (NDA) and approval of Vumerity is expected sometime in 2019.
Banner Life Sciences has received tentative FDA approval for Bafiertam (monomethyl fumarate) for relapsing forms of MS. Lopata discussed that Bafiertam is the active metabolite of both Tecfidera and Vumerity, and its launch is anticipated for June 2020. Celgene has submitted its NDA for ozanimod for the treatment of adults with relapsing forms of MS. The FDA previously rejected the NDA based on insufficient data, but it is expected to receive approval based on the new submission on March 25, 2020. Data is based on the SUNBEAM and RADIANCE trials, which demonstrated that ozanimod was effective at preventing MS relapses.
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Ozanimod is an oral sphingosine 1-phosphate (S1P) receptor modulator. “With a mechanism of action similar to the recently approved Mayzent (siponimod) and an optimal pharmacokinetic profile, ozanimod hopes to demonstrate an improved safety profile to Gilenya (fingolimod),” says Lopata. Ozanimod has only been studied in relapsing forms of MS; however, Mayzent is FDA approved for both relapsing and secondary progressive populations.
“With the success of Ocrevus (ocrelizumab) for MS, additional CD20-directed monoclonal antibodies are likely to follow,” says Lopata.
Another candidate on the horizon is ublituximab (TG-1101), which is being studied by the biopharmaceutical company TG Therapeutics. Ublituximab is a monoclonal antibody that targets the CD20 antigen, and anti-CD20 antibodies have been shown effective in treating various conditions including MS. The company recently announced phase 2 data at the AAN annual meeting showing that the drug is well tolerated. Phase 3 trials known as Ultimate 1 (NCT03277261) and Ultimate II (NCT03277248) are currently being conducted to assess the safety and efficacy in patients with relapsing MS.