December 18, 2020 News by Marta Figueiredo, PhD Mayzent Aids Cognitive Processing Speed in SPMS Patients, Trial Suggests Mayzent (siponimod) significantly improved cognitive processing speed in people with secondary progressive multiple sclerosis (SPMS) compared with a placebo, according to additional analyses ofĀ two-year data from the EXPAND Phase 3 trial. While…
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…
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…
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 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…
September 20, 2019 News by Ana Pena PhD #ECTRIMS2019 – Mayzent’s Benefits from a Patient Perspective a ‘Key Question,’ Says EXPAND’s Principal Investigator The most recent data continue to support Mayzent‘s (siponimod) benefits and provide more insights on how this therapy can make a difference for those with relapsing forms of multiple sclerosis (MS) ā in particular, data showing the therapy lowers the risk of becoming wheelchair-dependent. New results from…
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…
July 8, 2019 News by Jose Marques Lopes, PhD Mayzent Boosts Cognitive Processing Speed in SPMS Patients, Phase 3 Trial Data Show Treatment with Mayzent (siponimod) led to significant improvement in cognitive processing speed in patients with secondary progressive multiple sclerosis (SPMS), according to updated results of a Phase 3 trial. Novartisā findings, presented at the European Academy of Neurology (EAN) congressĀ that ran June 29āJuly 2 in Oslo,…
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…
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 27, 2018 News by Jose Marques Lopes, PhD #AAN2018 – Siponimod Lessens Risk of SPMS Progression Independent of Relapses, Trial Data Show Novartisā investigational oral treatmentĀ siponimod (BAF312) reduces the risk of disability progression in patients with secondary progressive multiple sclerosis (SPMS), a new analysis of Phase 3 trial results show. Using what the company describes as more accurate methods to assess siponimod effect’s on progression risk, necessary because the…
April 17, 2018 News by Alice MelĆ£o, MSc #AAN2018 ā Siponimod Reduces Disease Activity Biomarker in SPMS Patients Novartis‘ siponimod (BAF312) can reduce blood levels of a biomarker of nerve cell damage in patients with secondary progressive multiple sclerosis (SPMS), a Phase 3 clinical trial shows. Researchers will present the latest results of the ongoing trial at the 2018 annual meeting of the American Academy…
March 27, 2018 News by Alice MelĆ£o, MSc Siponimod Reduces Risk of SPMS Patients’ Disability Worsening, Phase 3 Trial Shows Siponimod (BAF312) reduces the risk of disability progression in patients withĀ secondary progressive multiple sclerosis (SPMS), a Phase 3 clinical trial shows. An article about theĀ NovartisĀ therapy’s trial resultsĀ appeared in the journal The Lancet. The title is āSiponimod versus placebo in secondary progressive multiple sclerosis…
October 30, 2017 News by Patricia Silva, PhD #MSParis2017 ā Promising Work in Pediatric and Secondary Progressive Patients Is Focus, Novartis Says in Interview Gilenya (fingolimod) lowered relapse rates in children and adolescents with relapsing multiple sclerosis at a “magnitude” ā almost 82 percent ā never before seen in a scientific study and could be “life changing” for these hard-to-treat patients, a top researcher withĀ Novartis, the treatment’s developer, said in an…
April 28, 2017 News by Joana Fernandes, PhD Siponimod Slows Progression of MS Disability, Phase 3 Clinical Trial Shows SiponimodĀ slows the progression of multiple sclerosis patients’ disability, a Phase 3 clinical trial indicates. The therapy reduced the risk of disability progression in patients with secondary progressive multiple sclerosis (SPMS) by 21 percent over three months, researchers said. At six months, the reduction was 26 percent, they said. Researchers…
September 21, 2016 News by Patricia Silva, PhD #ECTRIMS2016 – Novartis’s Siponimod Appears to Slow SPMS Progression in Phase 3 Study AĀ presentation at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016 Congress gave patients with progressive multiple sclerosis (MS) a reason for optimism, as Novartis reported that siponimod (BAF312) reduced the risk of disability progression in a Phase 3 study of patients with secondary progressive (SP) MS.
August 29, 2016 News by InĆŖs Martins, PhD Gilenya-like Therapy Shows Benefit in Secondary Progressive MS Patients in Phase 3 Trial Patients with secondary progressive multiple sclerosis (SPMS) who were treated with BAF312 (siponimod), a sphingosine-1-phosphate (S1P) inhibitor, in a Phase 3 clinical trial showed aĀ Ā significantly reduced risk for disability progression compared to placebo,Ā NovartisĀ recently announced. BAF312 is a selective modulator of specific types of the S1P receptor. This receptor is…