FDA Approves Zeposia® for Relapsing Forms of MS
On March 26, 2020, Bristol Myers Squibb announced that the United States Food and Drug Administration (FDA) approved Zeposia® (ozanimod) for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS). Zeposia is an oral medication given once daily as a 0.92 mg pill.
Patients taking Zeposia for the first time start with a titration, which means that it is begun at a lower dose and gradually increased until the full dose is reached. With this newly approved medication, starting at a lower dose reduces the risk of a transient decrease in heart rate and atrioventricular conduction delays, which may occur if a larger dose is introduced too quickly.
Zeposia is a sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. It joins two other previously approved S1P receptor modulators: Gilenya® (fingolimod) and Mayzent® (siponimod); additional S1P receptor modulators are also under investigation. Ponesimod is among those still under investigation and it was recently submitted to the FDA for approval. Zeposia is the only approved S1P receptor modulator that offers RMS patients an initiation that does not require a genetic test or label-based first-dose observation.
S1P receptor modulators are thought to work by blocking potentially damaging immune-system cells (lymphocytes) from leaving lymph nodes, lowering their number in the blood and tissues. These treatments may reduce damage to the central nervous system (CNS). In clinical trials of more than 2,600 adults with relapsing forms of MS, Zeposia was shown to have a significant effect on reducing the annual relapse rate (ARR) as well as the number of brain lesions, when compared to Avonex® (interferon beta-1a).
The most common adverse reactions occurring in 4% or more of the study participants include: upper respiratory infection; elevated liver enzymes, which could indicate inflammation; orthostatic hypotension, which is a sudden drop in blood pressure when changing position, such as when standing up from a sitting position; urinary tract infection; back pain; and high blood pressure. Warnings and precautions include an increased risk of infections, heart-rhythm issues, liver injury, fetal risk if pregnant while taking Zeposia, a decline in pulmonary (respiratory) function, and macular edema (swelling behind the eye). Additional warnings and limitations are specified in the prescribing information.
In light of the current COVID-19 pandemic and its impact on the country’s healthcare system, Bristol Myers Squibb is delaying the launch of Zeposia. For more information, please see MSAA’s full article. Individuals with questions may reach the BMS (Bristol Myers Squibb) Contact Center at (800) 321-1335.
FDA Approves Vumerity™ for Relapsing Forms of MS
On October 30, 2019, Biogen Inc. and Alkermes plc announced the United States Food and Drug Administration (FDA) approval of Vumerity™ (diroximel fumarate) oral capsules to treat adults with relapsing forms of multiple sclerosis (MS). This approval includes the treatment of clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS). This medication is taken by mouth twice daily.
Vumerity is in the same class of MS therapy as Biogen’s Tecfidera® (dimethyl fumarate), but is believed to cause fewer gastrointestinal (GI) side effects. The exact mechanism of action by which Vumerity exerts therapeutic effect in MS is not completely understood. However, upon entering the body, the medication is rapidly converted into the molecule monomethyl fumarate, which is the same active component found in Tecfidera. The monomethyl fumarate molecule is thought to activate an antioxidant protein that reduces oxidative stress, which in turn slows damage to protective nerve fibers in the brain.
When submitting Vumerity to the FDA for approval, study results comparing Vumerity to Tecfidera were included to establish bioequivalence, which refers to having the same active ingredients and resulting in similar effectiveness, safety, and side effects. The Phase III, open-label, two-year EVOLVE-MS-1 safety study in RRMS, along with pharmacokinetic bridging studies comparing Vumerity and Tecfidera, were used to demonstrate bioequivalence. EVOLVE-MS-2 (an elective Phase III, five-week, double-blind study) evaluated the gastrointestinal (GI) tolerability of Vumerity and Tecfidera.
In terms of effectiveness and safety, Tecfidera has been shown to reduce the rate of MS relapses, slow the progression of disability, and impact the number of MS brain lesions in people with relapsing forms of MS, while demonstrating a well-characterized safety profile. In terms of side effects, abdominal pain, diarrhea, and nausea were among the most common adverse events associated with Tecfidera in clinical trials. However, the “distinct chemical structure” of Vumerity that converts to the same active molecule as Tecfidera, reduces the incidence of gastrointestinal side effects.
Common side effects include flushing, redness, itching, or rash; nausea, vomiting, diarrhea, stomach pain, or indigestion. Warnings, side effects, and adverse events are similar to those listed for Tecfidera. Individuals with liver problems, kidney problems, low white blood cell counts or infection, as well as those who are pregnant, breastfeeding, or plan to become pregnant or breastfeed, should speak with their healthcare provider before taking Vumerity. Allergic reactions, PML (progressive multifocal leukoencephalopathy), decreases in white blood cell counts, and liver problems are among the potential serious adverse events that could occur.
FDA Approves Generic Versions of Gilenya®
On December 5, 2019, the United States Food and Drug Administration (FDA) announced that they had approved the applications from three separate pharmaceutical companies for the first generic versions of Gilenya® (fingolimod) capsules for the treatment of relapsing forms of multiple sclerosis (MS) in adult patients. Approved in September 2010, Gilenya was the first oral drug available for the long-term treatment of relapsing-remitting MS.
In May 2018, Gilenya became the first DMT also approved for the treatment of children and adolescents, ages 10 through 17, with relapsing forms of MS. At this time, Gilenya is the only DMT approved for this patient population, referred to as “pediatric MS.” However, the FDA states that this approval of the three generic applications is for relapsing forms of multiple sclerosis (MS) in adult patients, and does not specify if pediatric MS will be included within these medicines’ indications at this time.
The three pharmaceutical companies who received this approval of their generic Gilenya are HEC Pharm Co. Limited, Biocon Limited, and Sun Pharmaceutical Industries Limited. Further details on how soon these companies may market their generic versions of Gilenya and when these will be available to the MS community have not yet been announced. For more information, please see MSAA’s full article.
FDA Accepts Filing of Ofatumumab in the Treatment of RMS
On February 24, 2020, Novartis announced that the United States Food and Drug Administration (FDA) accepted the filing of ofatumumab, a novel B-cell therapy for adults with relapsing forms of MS. Ofatumumab is an anti-CD20 monoclonal antibody that has the potential advantage of being a human monoclonal antibody, versus using antibodies from non-human species that have been modified. Ofatumumab has a unique target on the CD20 molecule and is approved for certain forms of leukemia.
Two simultaneous Phase III clinical trials – ASCLEPIOS I and ASCLEPIOS II – compared the efficacy and safety of monthly subcutaneous ofatumumab (20mg) versus once-daily 14mg doses of oral Aubagio® (teriflunomide) in adults with RMS. In both the ASCLEPIOS I and ASCLEPIOS II studies, ofatumumab reduced the annual relapse rate by 50.5% and 58.5% respectively, significantly suppressed both gadolinium-enhancing T1 lesions and new or enlarging T2 lesions, and showed a relative risk reduction in three-month and six-month confirmed disability progression (CDP) in pre-specified pooled analyses. Novartis anticipates regulatory approval in June 2020.
For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.
Written by Susan Wells Courtney, MSAA Senior Writer
Sections from MSAA’s 2019 MS Research Update written by Tom Garry, Medical Writer
Reviewed by Barry A. Hendin, MD, MSAA Chief Medical Officer