March 18, 2022 News by Steve Bryson, PhD 3D Showing of Mayzent Binding to Receptor Could Advance Treatments For the first time, researchers have brought to light the precise three-dimensional structure ofĀ Mayzent (siponimod) as it binds to its molecular target, the sphingosine 1-phosphate receptor 1 (S1P1). These findings are expected to aid in developing next-generation MS therapeutics with better selectivity for S1P1, enhancing their potency while reducing…
February 28, 2022 Columns by Ed Tobias MS News That Caught My Eye Last Week: aHSCT, Skin Cancer, Spasticity, NfL Blood Test #ACTRIMS2022 ā Immune System āResetā by Stem Cell Transplant At the University of Ottawa, autologous hematopoietic stem cell transplantation (aHSCT) has been used to treat people with aggressive MS since the early 2000s, MS News Today‘s Marisa Wexler reports. This study, which reviewed 71 patients during that period, reports…
December 14, 2021 News by Marisa Wexler, MS Alliance Outlines Global Goals for Progressive MS Research and Care Leaders of theĀ International Progressive MS Alliance have proposed a global research strategy to find better ways to care for people with progressive forms of multiple sclerosis (MS). They detailed their proposal in the paper, “Charting a global research strategy for progressive MSāAn international progressive MS…
May 5, 2021 News by Marisa Wexler, MS Safety of Oral DMTs for RRMS in Real-world Use Seen to Match Trial Findings People with relapsing-remitting multiple sclerosis (RRMS) using approved oral disease-modifyingĀ therapiesĀ generally tolerate the treatments well, with real-world adverse event profiles similar to those seen in clinical trials, an analysis of U.S. data indicates. Results also suggest high adherence to these therapies ā meaning patients are usually taking the therapies…
December 30, 2020 Columns by Ed Tobias Will Reduced Treatment Time Keep Ocrevus Competitive? One of the key considerations when choosing a disease-modifying therapy (DMT) is how much it will disrupt your life. It’s one of several factors that need to be evaluated. Unlike shots and pills, infusion treatments can require a significant amount of time. That’s why the U.S. Federal Drug Administration’s December…
November 9, 2020 Columns by Ed Tobias MS News That Caught My Eye Last Week: Age and DMTs, Tysabri or Gilenya, Sativex Trial, Ocrevus and Mayzent Phase 3 Trial of Sativex, Cannabis Extract Treatment for MS Spasticity, Opens in US This is a major step toward making a clinically tested, cannabis-based medication available in the U.S. I’ve always thought that medications containing a THC/CBD combination are useful to lessen some MS symptoms, but the lack…
October 16, 2020 News by Marisa Wexler, MS Mayzent Approved for Active SPMS Patients in England and Wales Mayzent (siponimod) has become the first oral medication to be approved for people with active secondary progressive multiple sclerosis (SPMS) in England and Wales. Following this decision by England’s National Institute for Health and Care Excellence (NICE) ā which reversed itsĀ opinion announced in June ā the…
October 15, 2020 News by Forest Ray PhD Mayzent Approved for Active Secondary Progressive MS in Scotland The Scottish Medicines Consortium (SMC) has approved Mayzent (siponimod) for the treatment of active secondary progressive multiple sclerosis (SPMS) in Scotland. Mayzent, developed by Novartis, is a tablet taken once daily to counter a person’s disability progression. SPMS gradually develops from relapsing-remitting MS, and is…
July 29, 2020 News by Marisa Wexler, MS Canadian MS Working Group Updates Guidelines for Diagnosis, Treatment The Canadian MS Working Group (CMSWG) ā made up of neurologists with the Canadian Network of MS ClinicsĀ ā has updated its recommendations concerning diagnosis and the use of disease-modifying therapies (DMTs) for multiple sclerosis (MS), according to a press release from theĀ MS Society of Canada.
June 26, 2020 News by Marisa Wexler, MS NICE Does Not Favor Adding Mayzent to NHS England for Active SPMS TheĀ National Institute for Health and Care Excellence (NICE) is recommending againstĀ Mayzent (siponimod) as a treatment for active secondary progressive multiple sclerosis (SPMS) in the U.K., because its cost-effectiveness relative to an existing treatment for these patients is not known. NICE’s draft guidance for Mayzent is open…
April 22, 2020 News by Marisa Wexler, MS Starting Mayzent Early of Greater Benefit in SPMS, 5-Year Trial Data Show People with secondary progressive multiple sclerosis (SPMS) who began treatment with MayzentĀ early and continued its use for years are less likely to experience disability progression than those starting the medication later in their disease course, five-year data from the EXPAND study suggest. Data from this same Phase 3…
April 9, 2020 Columns by Jennifer (Jenn) Powell Zeposia Is Now Approved, But Expect Delays Zeposia’s recent approval in the U.S. is exciting news for all in the MS community. Unfortunately, we will need to table that excitement a bit longer. Despite its approval, the treatment’s commercial distribution will be delayed by the COVID-19 pandemic. I am confident, however, that it will be…
March 6, 2020 News by Iqra Mumal, MSc Health Canada Approves Mayzent to Treat Active SPMS Health Canada has approved Novartis‘sĀ MayzentĀ (siponimod)Ā for the treatment of adults with activeĀ secondary progressive multiple sclerosisĀ (SPMS) to delay the progression of physical disability. Active disease is determined either by the presence of relapses or magnetic resonance imaging features characteristic of inflammatory activity. Multiple sclerosis (MS)…
January 24, 2020 News by Patricia Inacio, PhD Mayzent Helps Regulate the Immune System in SPMS, Study Shows Mayzent (siponimod), an approved oral therapy for activeĀ secondary progressive multiple sclerosisĀ (SPMS), promotes a more regulatory immune system, which may explain its added benefits for SPMS, new clinical data show. The study āSiponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosisā was published in the…
January 21, 2020 News by Marta Figueiredo, PhD Mayzent Approved in Europe as First Oral Treatment for Active Secondary Progressive MS TheĀ European CommissionĀ has approvedĀ Novartis‘s MayzentĀ (siponimod) as the first oral treatment for adults with active secondary progressive multiple sclerosisĀ (SPMS). Active SPMS is defined by the presence of evident relapses or the detection of inflammatory activity in brain lesions on imaging scans. āAs the only indicated oral therapy proven for…
November 18, 2019 News by Iqra Mumal, MSc Mayzent Approved in Australia as First Treatment for Secondary Progressive MS Novartisās MayzentĀ (siponimod) has been approved by Australiaās Therapeutic Goods Administration (TGA) for the treatment of secondary progressive multiple sclerosis (SPMS), making it the first therapy to be approved for this use in Australia. SPMS is a form of MS that develops after the onset of…
November 15, 2019 News by Grace Frank CHMP Favors Mayzent as Oral Treatment Specifically for Active SPMS Patients in EU The Committee for Medicinal Products for Human Use (CHMP) issued an opinion supporting MayzentĀ (siponimod) as an oral treatment specifically for adults with active secondary progressive multiple sclerosisĀ (SPMS) in the European Union. Opinions released by CHMP, an arm of the European Medicines Agency (EMA), carry weight and are…
September 23, 2019 Columns by Ed Tobias MS News that Caught My Eye Last Week: Ozanimod, Achtar Gel, Onset Age Progression Link, Glial Cells Could Differentiate MS Types In this column, I take a look at more exciting research from the ECTRIMS2019 conference this month. #ECTRIMS2019 ā Ozanimodās āKey Advantagesā May Lead to New First-line MS Therapy: Interview with Neurologist Jeffrey Cohen This year we’ve seen the approval of two new multiple sclerosis treatments in the United…
September 16, 2019 News by Ana Pena PhD #ECTRIMS2019 – Mayzent Reduces Risk of SPMS Patients Becoming Wheelchair Bound, Data Show Mayzent (siponimod) reduces the risk of people with secondary progressive multiple sclerosis (SPMS) becoming dependent on a wheelchair, a new analysis of the EXPAND study shows. These findings further corroborate prior trial data demonstrating that Mayzent use delays disability progression and cognitive decline in SPMS patients. The results…
August 16, 2019 News by Marisa Wexler, MS MS Therapies Among Limited Offerings Through AllianceRx Walgreens Prime Medications for treating certain rare and chronic conditions, Ā including multiple sclerosis (MS), are now available from the specialty and home delivery pharmacy AllianceRx Walgreens Prime, the company announced. The newly included specialty medications are all limited distribution drugs (LDDs), which means the drug manufacturers have signed agreements giving very…
August 2, 2019 Columns by Ed Tobias Using the Floodlight App to Track My MS Over the past several weeks, I’ve been using an app called Floodlight to track my ability to live with my multiple sclerosis (MS). It measures things such as my balance, finger dexterity, walking speed, and cognitive ability. It even knows if I’m keeping myself shuttered in my apartment or…
July 17, 2019 News by Ana Pena PhD Phase 3 Trial of Ibudilast Planned for SPMS Patients with Inactive Disease, MediciNova Says A Phase 3 trial is planned to confirm the safety and efficacy of oral ibudilast (MN-166) in treating people with secondary progressive multiple sclerosis (SPMS) without relapses, or those whose disease is not active, MediciNovaĀ announced. Data from this single Phase 3 study may be used to request…
July 2, 2019 News by Ana Pena PhD Neurologists Prefer Mayzent for SPMS and RRMS, But Mavenclad Could Be ‘Ideal’ First Switch, Report Suggests While neurologists favor Novartis‘ Mayzent (siponimod) for people with active secondary progressive multiple sclerosis (SPMS) and transitioning relapsing-remitting MS (RRMS), EMD Serono‘s Mavenclad (cladribine) could serve as a first option for patients with RRMS who failed initial therapy, Spherix Global Insights says in its…
May 9, 2019 News by Jose Marques Lopes, PhD #AANAM – Mayzent Improves Cognitive Processing Speed in SPMS Patients, Trial Results Show Treatment with Mayzent (siponimod) provided sustained improvements and prevented deterioration of cognitive processing speed in patients with secondary progressive multiple sclerosis (SPMS), regardless of their cognitive function prior to therapy, according to results of a Phase 3 clinical trial. The data were presented at the recent 2019Ā American…
May 7, 2019 News by Jose Marques Lopes, PhD #AANAM – Mayzent Lessens Inflammation at Brain Meninges, Prevents Migration of Lymphocytes to Reduce Demyelination, Mouse Study Suggests Treatment with Mayzent (siponomod) may reduce myelin deterioration by lessening the accumulation of immune cells in brain meninges, and preventing the migration of pro-inflammatory lymphocytes into the brain, according to a study in a mouse model of multiple sclerosis (MS). The research, āA Mouse Model of…
April 18, 2019 Columns by Jennifer (Jenn) Powell The DMT Decision: Tried and True or Shiny and New? I spend a great deal of time in my head. I think. A lot. Perhaps I do so more than I should, but then again, it is a haven at times. My thoughts run the gamut from the serious to the inane. Today my thoughts…
April 3, 2019 News by Marisa Wexler, MS Cleveland Clinic Neurologist Applauds Mayzent’s FDA Approval, But Surprised by Those It May Not Treat When theĀ U.S. Food and Drug Administration approvedĀ the disease-modifying therapy Mayzent forĀ relapsing types of multiple sclerosis, itĀ specified in its label that the treatment was for people withĀ clinically isolated syndrome, relapsing-remitting MS, and ā importantly āĀ secondary progressive MSĀ provided they have "active" disease. The approval is good news, an MS researcher and physician saidĀ toĀ Multiple Sclerosis News TodayĀ in an interview, but "surprising" in that the FDA's decision was largely based on a trial that didn't involve CIS patients and wasn't focused on responses among particular types of SPMS. āIt's the first time that I've seen in the MSĀ field that regulatorsĀ made an approval designation ā activeĀ secondary progressive MS ā based on an underpowered subgroupĀ analysis,ā saidĀ Robert Fox, MD, a neurologist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. Novartis'Ā medication, as a first oral therapy approved in the U.S. forĀ a form ofĀ SPMS,Ā is a big step forward in MS treatment, he said. But details of the FDA's decisionĀ caughtĀ him off guard. Fox served on the steering committee for the EXPAND Phase 3 clinical trial ,Ā on which the FDA decision was largely based.Ā His clinic was also one of the sites treating and evaluating patients in this pivotal study. Results of the EXPAND trial showed thatĀ Mayzent could reduce the risk of disability progression at three months (the trialās primary endpoint, or goal) by 21% in treatedĀ SPMS patients, compared to those given aĀ placebo. Among those with active SPMS (meaning with relapses), a 33% reduction was observed. The treatment, an S1P modulator that works in part to keep lymphocytes from entering the brain to trigger inflammation,Ā alsoĀ decreased the annualized relapse rate by 55% and improved cognitive processing speed in all treated patients.Ā āWhat was found, and I think quite clearly found in a large-size study, was that siponimod in patients with secondary progressive MS clearly slowed the progression of clinical disability over the course of the trial,ā Fox said. āIt's a statistical concept ā obviously patients either progress or they don't progress ā but on an overall basis there was a 21% slowing in the rate of progression of clinical disability.ā The FDAās decision is particularly important for SPMS patients. While Ocrevus (ocrelizumab) alsoĀ treats all relapsing MS forms and people with primary progressive disease (PPMS), it's an intravenous therapy given every six months. Mavenclad (cladribine), approved for relapsing patients in the U.S. just days after Mayzent, is another oral and active disease therapy. To Fox, Mayzent seemed to reach beyond only those secondary progressive patients with clinically active disease. āReally, this is the only drug that's been found to be effective in secondary progressive MS," he said. āTo that degree, it stands alone.ā That's why two points in the FDA's decisionĀ surprised him. The firstĀ is the label's specific mention of clinically isolated syndrome. CISĀ is defined asĀ theĀ first clinical presentationĀ of this diseaseĀ ā aĀ neurological episode that lasts at least 24 hours, and is characterized by inflammatory demyelination (the loss of myelin, the protective coat surrounding neurons). Ā For clinicians like Fox, CIS is a first manifestation of MS ā a kind of "mono sclerosis."Ā Since thereās only one documented attack, it canāt yet be considered multiple sclerosis, āas the multiple hasn't happened,ā Fox said, but many "in the field consider CIS to be ā¦ an early stage of MS." āIf the patient has a whole bunch of lesions on their brain [as seen on an MRI scan] and they had a single clinical event, ah, probably, they have MS,ā he said. Regulatory bodies like the FDA,Ā however,Ā have historically considered CIS to be its own separate entity. That makes this decision doubly surprising, according to Fox, since the EXPAND trial only enrolled patients with SPMS, not CIS. Ā āIt's the first time I've seen them approve for CIS specifically when there wasn't a trial in CIS,āĀ Fox said. āI agree with it ā I don't have a problem with it ā it just surprised me that the regulators were so progressive in their appreciation of MS.ā The second ā and far more unsettling ā surpriseĀ wasĀ the FDAās decision toĀ only approve Mayzent for āactiveā SPMS patients, instead of all SPMS patients. This decision didnāt come out of nowhere, he noted, but it remains puzzling in the context of the EXPAND trial.Ā InĀ compiling trial results, investigators did a subgroup analysis ā as they often do, almost as an aside for research reasons ā and found more favorableĀ responses to Mayzent treatmentĀ in patients with active inflammation beforeĀ the trial's start, those it determined to be with "active" disease. Ā āThere was a third of patients who had a relapse in the two years prior to enrollment, and those patients actually had a 30% slowing in disability progression, compared to the 21% overall,ā Fox said. This certainly does suggest that Mayzent can be more effective in people with active disease ā but there's a catch. The trial itself was not designed to make such a distinction. It enrolled SPMS patients regardless of activity, and its priority goal was changes in disease progression across all who were treated with Mayzent or given a placebo. Ā āWhat's important is that the trial was powered for the overall outcome. It was not powered for subgroup analysis,ā Fox said,Ā considering this a crucial point.Ā In clinical studies, being āpoweredā refers to theĀ enrollingĀ of whatever specific number of participants a study needs to ensureĀ itsĀ results will reach statistical significance. More people are redundant and, as such, an unnecessary cost; fewer could mean that trial's conclusions cannot be supported by rigorous scientific measures.Ā In other words, Fox said, the only conclusions that can be drawn from the EXPAND study reliably ā with rigor ā are based on data drawn from all its SPMSĀ patients, not aĀ subgroup with active disease. This trial āfollowed over 1,600 patients for the clinicalĀ disability. These are purposely powered so that you're not following twice as many people as you need toĀ ā¦ you're powered for that primary outcome,ā he said. āSo, how could they [the FDA] look at a subgroupĀ analysis and make an approval decision based on a subgroupĀ analysis that was underpowered?ā The neurologist gave as examplesĀ other subgroup differences found in trial analyses that didn't affect regulatory approval ā but to his mind, equally could have.Ā One was an analysis findingĀ female SPMS patients respondedĀ to the therapy better than males,Ā showing lesser disease progression. "So why didn't they just approve it for the females and not the males?" Fox asked. But, when asked, Fox did not think the labelĀ toĀ necessarily be an error. "My point is the absurdity of it," he said. "How could they make the regulatory approval based on a subgroupĀ analysis that wasn't powered for conclusions?" He was also particularly troubled becauseĀ the FDAĀ ādidn't define what āactiveā means āĀ is it just a relapse, or is it MRI disease activity?"Ā For many clinicians, āactiveā SPMS refers to ongoing inflammation that can be observed on MRI (magnetic resonance imaging) scans. In EXPAND, however, the active subgroup was defined as patients with clinical relapses within two years of being enrolled in the trial. Fox worries about this apparent lack of a regulatory definition of "active" SPMS, since āobviously, the insurance companies are going to seize upon that, and they're going to look for every way they can to avoid covering it for patients.ā Mayzent, Fox agreed,Ā is likely to be expensive. The therapy is reported to carry a U.S. list price ofĀ $88,500 a year. āI always have a concern about the cost of these drugs. They're all fearfully expensive,ā he said, noting he treats SPMS patients. His focus now is on working to ensure that possible regulatory and financial hurdles wonāt pose too much of an obstacle for patients, especially those with SPMS. āI don't know what the insurance companies are going to do with this, but I'm hoping that it is available for my patients, and I say that as their clinician,ā Fox concluded.
April 2, 2019 Columns by Ed Tobias Mayzent Joins the MS Medication Arsenal, But I Have Questions As you might have heard, a disease-modifying therapy (DMT) for patients with active secondary progressive multiple sclerosis (SPMS) was approved a few days ago. That’s great news. A medication targeting SPMS is overdue, but it could be better. The DMT is Mayzent (siponimod), a tablet that’s taken…
March 28, 2019 News by Larry Luxner MS Patient Groups React Favorably to Mayzent Approval, But Question Therapyās Price Tag National organizations that represent patients with multiple sclerosisĀ (MS) welcome the U.S. Food and Drug Administration’s March 26 approvalĀ of Novartis’Ā oral therapy MayzentĀ (siponimod) ā but they complain that, at $88,500 per year, the treatment is overpriced. The Multiple Sclerosis Society of AmericaĀ (MSSA) is clearly upbeat about the…
March 27, 2019 News by Patricia Inacio, PhD FDA Approves Novartis’ Mayzent for Relapsing Forms of Multiple Sclerosis, Including Active SPMS The U.S. Food and Drug Administration (FDA) has approved Novartis’ Mayzent (siponimod) oral tablets for adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting disease (RRMS), and active secondary progressive disease (SPMS). Mayzent was designed to inhibit the activity of…