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FDA Approves Siponimod - Brand named Mayzent® - for Relapsing Forms of MS Including Active Secondary Progressive MS UPDATE

March 26, 2019

UPDATED on 3/27/19 with additional details and FAQs
  • The U.S. Food and Drug Administration has approved oral siponimod (brand named Mayzent,® Novartis International AG) for the treatment of adults with clinically isolated syndrome (an initial neurological episode) and relapsing forms of MS, including those with active secondary progressive MS. This means people who have had progression of disability but still experience acute relapses or new MRI activity.
  • In a large clinical trial of 1651 people with secondary-progressive MS, fewer people taking Mayzent had confirmed worsening of disability progression compared to those on placebo. Mayzent also decreased the number of relapses. According to the prescribing information, the participants with non-active secondary progressive MS did not show significant benefits.
  • Mayzent is an FDA-approved immune system-modulating therapy, taken by mouth once daily, which was designed to be more selective than Gilenya® (fingolimod, Novartis International AG International AG) and potentially have fewer risks. Mayzent is thought to act by retaining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and out of the the central nervous system. Mayzent also enters the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory and/or other effects.
  • This approval provides another treatment option for people living with relapsing forms of MS and specifically includes people with secondary progressive MS who are continuing to experience active disease.
  • The most common adverse reactions reported during clinical trials included headache, high blood pressure, and increases in liver function tests. Mayzent may increase the risk of infections, may cause macular edema (swelling in the back of the eye), and may cause transient decreases in heart rate and a decline in lung function. The prescription label will have advice about tests people should undergo before beginning to take Mayzent. 
“This is an important breakthrough for people with secondary progressive MS, a type of MS that follows relapsing-remitting MS and is characterized by a worsening of symptoms and disability over time,” said Kathy Costello, MS, ANP-BC, MSCN, Associate Vice President of Healthcare Access at the National MS Society. “We are grateful that there is a new treatment option for people with active secondary progressive MS, and we are hopeful that this approval will stimulate development of more treatments for progressive MS.”
 
Read the FDA’s press release
Download the full prescribing information and Medication Guide (.pdf)
 
DETAILS
The FDA has approved Mayzent (siponimod - Novartis International AG) for use in the treatment of adults with relapsing forms of MS, including clinically isolated syndrome (an initial neurological episode), relapsing-remitting MS, and active secondary progressive MS. People with active secondary progressive MS have had progression of disability but still experience acute relapses or new MRI activity. In the clinical trial, people who had secondary progressive MS and who had experienced at least one relapse within two years before entering the study were considered “active.”
  • Mayzent will be available as a first-line treatment, which means that there are no recommendations in the approved labeling for people to try other MS therapies before taking it.
  • There is no requirement for first-dose monitoring in a health facility except for individuals with pre-existing heart conditions.
  • There are recommendations for several lab and clinical tests prior to the first dose,
  • Mayzent was approved for use in adults, and has not been tested in children with MS.  
About Secondary Progressive MS: Secondary progressive MS follows an initial relapsing-remitting course. Many people who are initially diagnosed with relapsing-remitting MS eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function over time. Some people with secondary progressive MS can be characterized as either active (with relapses and/or evidence of new MRI activity) or not active, as well as with progression or without progression. The reason for these distinctions in disease course is that in the U.S., there are many disease-modifying therapies approved by the FDA for use in “relapsing forms” of MS, which includes those individuals who have secondary progressive MS and continue to have relapses and/or evidence of disease activity on MRI.
 
About Mayzent: Mayzent is an FDA-approved immune system-modulating therapy that was designed to be more selective than Gilenya® (fingolimod, Novartis International AG International AG). Gilenya is approved for adults and children aged 10 years or older with relapsing forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability. Mayzent is thought to act by retaining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and from entering the central nervous system. Mayzent also enters the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory and/or other effects.
 
Potential Benefits: Results of a 60-month, phase III clinical trial of Mayzent, involving 1,651 people with secondary progressive MS, were published in The Lancet in March 2018. The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Overall, those taking Mayzent had a 21% reduced risk of disability progression compared to those on placebo. According to the prescribing information, Mayzent significantly reduced the risk of progression in those with active secondary progressive MS, but not in those who had non-active secondary progressive MS. Secondary endpoints suggested that those on active therapy had 23% lower average change in brain volume, reduced relapse rates, and reduced MRI-detected lesion volume.
 
Potential Risks: The most common adverse reactions reported during clinical trials included headache, high blood pressure, and increases in liver function tests. The serious adverse events reported to be more likely for those taking Mayzent included nervous system disorders and infections. Mayzent is not recommended for people with certain types of heart conditions.
 
Prescribing information includes several warnings and precautions, including the following. Mayzent:
  • reduces white blood counts, and so may increase the risk of infections, including serious infections
  • may cause macular edema (swelling in the back of the eye)
  • may cause transient decreases in heart rate
  • may reduce lung function
  • may cause liver injury
  • may increase blood pressure
  • may cause harm to a fetus, so women of childbearing potential should use contraception during and for 10 days after stopping Mayzent. 
The Mayzent Medication Guide (pages 22-25 of the document) provides advice about symptoms to be alert to and about which individuals taking Mayzent should inform their healthcare providers.
 
Pre-dosing Tests and Evaluations: The prescribing information contains advice to health care providers about tests people should undergo before beginning to take Mayzent. These include:
  • Genetic blood test to determine the person’s CYP2C9 genotype, because people with some variants of these genes would need a different dose of Mayzent or should not take it at all.
  • Other blood tests including a complete blood count and liver function tests,
  • Eye examination
  • Electrocardiogram/cardiac evaluation.
  • Blood test for antibodies to varicella zoster virus (Shingles virus). In those who are negative, VZV vaccination is recommended.
  • History of current or prior immune-suppressing medications, which may cause Mayzent to further reduce the ability to fight infections. 
First Dose: Most people without pre-existing heart conditions will receive a starter pack of tablets that gradually increases the daily dose over 5 days, before taking the full recommended daily dose. People with certain pre-existing heart conditions will need 6-hour or possibly longer heart monitoring when receiving their first dose of Mayzent.
 
For people who qualify, Novartis plans to offer patient assistance programs through The Novartis Patient Assistance Foundation: 1-800-277-2254 or https://www.pharma.us.novartis.com/our-products/patient-assistance/patient-assistance-foundation-enrollment.
 
Resources:
Read the FDA’s press release
Download the full prescribing information and Medication Guide (.pdf)
 
Mayzent is a registered trademark of Novartis International AG.
Gilenya is a registered trademark of Novartis International AG
 

Frequently Asked Questions About Mayzent Approval 

Q. What types of MS is Mayzent approved to treat?
A. The FDA has approved Mayzent for the treatment of adults with clinically isolated syndrome (an initial neurological episode), and relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. People with active secondary progressive MS have had progression of disability but still experience acute relapses or new MRI activity. In the clinical trial, people who had secondary progressive MS and who had experienced at least one relapse within two years before entering the study were considered “active.”
 
Q. Who might benefit from Mayzent?
A. The approval includes clinically isolated syndrome and relapsing forms of MS, including relapsing remitting MS and active secondary progressive MS. According to the prescribing information, Mayzent significantly reduced the risk of progression in those with active secondary progressive MS, but not in those who had non-active (without relapses) secondary progressive MS.
 
Like all clinical trials, the trial of Mayzent in secondary progressive MS limited the characteristics of people who could participate. The trial only included people who were aged 18 to 60, who had an EDSS (Expanded Disability Status Scale – a scale to assess neurological functioning used in clinical trials) score of 3.0 (meaning they were fully ambulatory but had  other functional limitations) up to 6.5 (meaning they were able to walk with the help of a walker or bilateral crutches or other devices on both sides). It is not possible to predict how a specific individual will respond to treatment. The use of Mayzent in clinical practice will help determine who is likely to benefit.
 
Q. How is Mayzent taken?
A. Mayzent is a tablet administered by mouth once daily.
 
Q. When will Mayzent be available by prescription?
A. According to Novartis, people may talk to their MS healthcare providers now about taking Mayzent. The company expects supplies of the therapy to be available within a week of the approval. Accessing the medication also depends on issues related to an individual’s health insurance.
 
Q. Are there other therapies available for people with secondary progressive MS?
A. Yes, depending on the type of secondary progressive MS they have. Secondary progressive MS follows an initial relapsing-remitting course. Many people who are initially diagnosed with relapsing-remitting MS eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function over time. Some people with secondary progressive MS can be characterized as either active (with relapses and/or evidence of new MRI activity) or not active, as well as with progression or without progression. Many available disease-modifying therapies are approved for use in “relapsing forms” of MS, which includes those individuals who have secondary progressive MS and who continue to have relapses and/or evidence of disease activity on MRI.
 
Q. Should individuals with relapsing forms of MS switch from their current therapy to Mayzent?
A. The decision about whether to take Mayzent should be made in collaboration with the healthcare provider treating your MS, taking into account a variety of factors including the effectiveness of any therapy you are currently using, the potential risks and benefits, as well as costs and lifestyle factors. Important questions to be considered and discussed with your healthcare provider in terms of Mayzent include:
  • What health conditions do I have that might discourage the switch to Mayzent?
  • How am I doing on my current therapy?
  • What is my tolerance for the risk of known side effects?
  • What is my tolerance for the risk of adverse consequences that might emerge with longer-term use?
  • How will my medication choice affect my ability or plans to become pregnant?  
Q. If I have been taking another disease-modifying therapy for MS, how long will I have to wait before starting ?
A.  Mayzent clears out of the system 10 days after the last dose. A decision to wait or proceed after that time needs to be made in collaboration with your MS healthcare provider
 
Q. Has Mayzent been proven to be more effective than other disease-modifying therapies?
A. There is no evidence yet to answer this question, since Mayzent has only been compared to inactive placebo in clinical trials.
 
Q. How long would a person take Mayzent?
A. There is no specified time limit for taking Mayzent. As with other disease-modifying medications, Mayzent would likely be continued if the person’s MS is stable, and she/he is experiencing no adverse events or new safety issues that could be ascribed to the medication.
 
Q. Will people taking have to get any special medical tests or monitoring?
A. Yes. The prescribing information contains advice to health care providers about tests people should undergo before beginning to take Mayzent. These include:
  • Blood test for genetic testing to determine the person’s CYP2C9 genotype, because people with some variants of these genes would need a different dose of Mayzent or should not take it at all.
  • Blood test for complete blood count and liver enzymes
  • Eye examination
  • Electrocardiogram/cardiac evaluation
  • Blood test for antibodies to varicella zoster virus. In those who are negative, VZV vaccination is recommended.
  • History of current or prior immune-suppressing medications, which may cause Mayzent to further reduce the ability to fight infections. 
First Dose: Most people without pre-existing heart conditions will receive a starter pack of tablets that gradually increases the daily dose over 5 days, before taking the full recommended daily dose. People with certain pre-existing heart conditions will need 6-hour or possibly longer heart monitoring when receiving their first dose of Mayzent.
 
Q. Will Mayzent help my mobility, prevent me from getting worse or reverse my progressive disability?
A. Based on results from the clinical trials, Mayzent is likely to help stabilize a person’s disability progression. We do not know if will reverse an individual’s disability. In the phase 3 trial for secondary progressive MS, treatment with Mayzent significantly reduced the risk of progression of clinical disability. This reduced risk of progression means that as a group, people taking Mayzent were 21% less likely to demonstrate worsening of disability than people taking placebo. However, it is not possible to predict how any one individual will respond to this or any other therapy.
 
Q. What will Mayzent cost?
A. The wholesale acquisition cost (WAC) of Mayzent is $88,500 per year. However, the price to an individual who has MS will depend on the provisions of his or her insurance coverage and the degree to which that individual will be eligible for programs designed to assist with out-of-pocket costs. Coverage will depend on individual insurance plans. For people who qualify, Novartis plans to offer patient assistance programs through The Novartis Patient Assistance Foundation: 1-800-277-2254 or https://www.pharma.us.novartis.com/our-products/patient-assistance/patient-assistance-foundation-enrollment.  
 
Q. Are there other therapies in development for progressive MS?
A. Yes. The National MS Society is closely watching experimental treatments in development for people with progressive forms of MS. In addition, other studies include:
  • Investigators at Oregon Health & Science University are conducting a Phase 2 clinical trial to determine if the oral supplement, lipoic acid, is an effective treatment for progressive forms of MS. The trial is co-funded by the Veteran’s Administration and the National MS Society.
  • The SPRINT-MS trial of Ibudilast, an oral anti-inflammatory agent, demonstrated that it was well tolerated and significantly slowed the rate of brain atrophy compared to placebo in people with secondary progressive and primary progressive MS. This trial was a unique collaboration between NIH's NeuroNEXT Network, MediciNova, and the National MS Society.
  • The MS-STAT2 study is underway at University College London, a multicenter trial testing whether a repurposed cholesterol-lowering therapy can slow the course of secondary progressive MS; the Society is providing funding. 
The Society is also very interested in wellness research to identify exercise, dietary and other approaches that will help people who have MS live their best lives. The Society supports several clinical trials that are investigating dietary interventions for symptom management and for their potential to modify the disease process.
 
Q: Based on these trial results, is there still a need to invest in additional research on progressive MS?
A:  Yes. We need to continue our investment in research to find solutions for progressive MS.  We welcome this development, but we must remain focused on finding more and better solutions for treating progressive MS. We will do this by our continued leadership in the International Progressive MS Alliance and by funding research on progressive MS through our own research programs, and by encouraging other companies to commit to developing treatments for progressive forms of MS.
 

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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