FDA approval for Mayzent® (siponimod), the first oral drug to treat secondary progressive MS with active disease
EAST HANOVER, N.J., March 27, 2019 /PRNewswire/ -- Novartis today announced that the US Food and Drug Administration (FDA) has approved Mayzent® (siponimod) for the treatment of relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome (CIS, is defined as a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination in the central nervous system (CNS)), relapsing remitting disease, and active secondary progressive disease, in adults. SPMS is a debilitating form of multiple sclerosis (MS) characterized by progressive and irreversible neurological disability. Mayzent is expected to be available in the US in approximately one week. Patients will not require a first dose observation (FDO, cardiac monitoring upon initiation) unless they have certain pre-existing cardiac conditions.
"Delaying disability progression is a critical goal of MS treatment, and historically, patients with advancing disease have had very few options to help them," said Fabrice Chouraqui, President, Novartis Pharmaceuticals Corporation. "We've had a longstanding mission to enhance the understanding of MS and help reimagine treatment options, and we're excited to expand on our legacy with Mayzent for patients with relapsing forms of MS, including SPMS with active disease."
Most patients transition from RRMS to SPMS over time. Therefore, starting therapy early is critical for patients to help slow the rate of disability progression. Disability progression most frequently includes – but is not limited to – an impact on ambulation, which could lead to patients needing a walking aid or a wheelchair.
"We are grateful that there is a new treatment option for adults with active secondary progressive MS," said Bruce Bebo, PhD, Executive Vice President, Research, National MS Society. "We are hopeful this approval will stimulate a conversation between patients and healthcare professionals about disability progression after relapsing remitting MS and its early management."
The approval of Mayzent is based on results from the Phase III EXPAND study, a randomized, double-blind, placebo-controlled study, comparing the efficacy and safety of Mayzent versus placebo in people living with SPMS. Patients enrolled in EXPAND were representative of a typical SPMS population: at study initiation, patients had a mean age of 48 years, had been living with MS for approximately 16 years and more than 50% had a median Expanded Disability Status Scale (EDSS) score of 6.0 and relied on a walking aid. Mayzent significantly reduced the risk of three-month confirmed disability progression (CDP) (primary endpoint; 21% reduction versus placebo, p=0.013; 33% reduction versus placebo in patients with relapse activity in the two years prior to screening, p=0.01). Mayzent also reduced the annualized relapse rate (ARR) by 55%.
Most common adverse reactions (incidence greater than 10%) are headache, hypertension, and transaminase increase.
"With the approval of Mayzent, we now have a much-needed therapeutic option to address SPMS with active disease," said EXPAND Steering Committee member Bruce Cree, MD, PhD, MAS, Clinical Research Director and George A. Zimmermann Endowed Professor in Multiple Sclerosis, University of California, San Francisco, School of Medicine. "Importantly, healthcare professionals now have even more reason to help patients identify changing symptoms and uncover early signs of progression."
Novartis is committed to bringing Mayzent to patients worldwide, and additional regulatory filings are currently underway with other health authorities outside the US. Regulatory action for Mayzent in the European Union is anticipated in late 2019, with additional regulatory action anticipated in Switzerland, Japan, Australia, and Canada this year.
About the EXPAND Study
EXPAND is a randomized, double-blind, placebo-controlled Phase III study, comparing the efficacy and safety of Mayzent versus placebo in people with SPMS with varying levels of disability, EDSS scores of 3·0–6·5. It is the largest randomized, prospective, controlled study in SPMS to date, including 1,651 people with a diagnosis of SPMS from 31 countries. Mayzent demonstrated a safety profile that was overall consistent with the known effects of S1P receptor modulation. It reduced the risk of three-month CDP by a statistically significant 21% (p=0.013; primary endpoint). CDP was defined as a 1-point increase in EDSS, if the baseline score was 3·0–5·0, or a 0·5-point increase, if the baseline score was 5·5–6·5. No significant differences were found in the T25FW, however, T2 lesion volume was reduced by 79% as compared to placebo. Additional secondary endpoints data included a 55% relative reduction in ARR and, compared to placebo, more patients were free from gadolinium-enhancing lesions (89%) and from new or enlarging T2 lesions (57%).
About Mayzent® (siponimod)
Mayzent is a next generation, selective sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome (CIS, is defined as a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination in the central nervous system (CNS)), relapsing remitting disease, and active secondary progressive disease, in adults. Mayzent selectively binds to S1P1 and S1P5 receptors. In relation to the S1P1 receptor, it prevents the lymphocytes from egressing the lymph nodes and as a consequence, from entering the CNS of patients with MS. This leads to the anti-inflammatory effects of Mayzent. Mayzent also enters the CNS and directly binds to the S1P5 and S1P1 sub-receptors on specific cells in the CNS (oligodendrocytes and astrocytes) to prevent inflammation.
About Multiple Sclerosis
MS is a chronic disorder of the CNS that affects around 400,000 people in the US. Patients can be diagnosed with the following types of MS: RRMS (the most common form of the condition at diagnosis), SPMS and primary progressive MS (PPMS). MS disrupts the normal functioning of the brain, optic nerves and spinal cord through inflammation and tissue loss. SPMS follows an initial form of RRMS, which accounts for approximately 85% of all MS diagnoses, and is characterized by gradual worsening of neurological function over time. This leads to a progressive accumulation of neurological disability. There remains a high unmet need for safe and effective treatments to help delay disability progression in SPMS with active disease (with relapses and/or evidence of new MRI activity).
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