interview

An Interview With My Primary Carer

Iā€™ve been meaning to do this for a while. My wife, Jane, whoā€™s also my primary MS carer, went away for a few days last week, and with absence making the heart grow fonder and all that, I thought Iā€™d strike ā€” if she came back! Fortunately, she did,…

#ECTRIMS2019 – Ahead for Mavenclad: Fuller Understanding of What Makes It ‘Unique,’ Serono Exec Says in Interview

Real-world data continues to support the safety and effectiveness ofĀ MavencladĀ (cladribineĀ tablets) in treating multiple sclerosis (MS), and several studies underway will help scientists gain in-depth understanding of how Mavenclad works, its impact on the immune system, and the durability of its benefits, an executive with EMD SeronoĀ said in an…

Mayzent ‘Will Change Lives’ of MS Patients Transitioning to SPMS, Novartis Says

The “regulatory environment” favoredĀ Mayzent (siponimod) beingĀ approved as an oral treatment for people withĀ relapsing multiple sclerosis (MS) ā€” specifically,Ā clinically isolated syndromeĀ (CIS),Ā relapsing-remitting multiple sclerosisĀ (RRMS), and activeĀ secondary progressive MSĀ (SPMS) ā€” a top executive with NovartisĀ said, althoughĀ the pharmaceutical company had requested a label covering all with SPMS. Dan…

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 ā€”Ā 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. ā€œIt'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 trialā€™s 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  ā€œWhat 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. ā€œIt'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 FDAā€™s 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. ā€œReally, this is the only drug that's been found to be effective in secondary progressive MS," he said. ā€œTo 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 thereā€™s only one documented attack, it canā€™t yet be considered multiple sclerosis, ā€œas the multiple hasn't happened,ā€ Fox said, but many "in the field consider CIS to be ā€¦ an early stage of MS." ā€œIf 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  ā€œIt's the first time I've seen them approve for CIS specifically when there wasn't a trial in CIS,ā€Ā Fox said. ā€œI 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 FDAā€™s decision toĀ only approve Mayzent for ā€œactiveā€ SPMS patients, instead of all SPMS patients. This decision didnā€™t 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  ā€œThere 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  ā€œWhat'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 ā€œpoweredā€ 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 ā€œfollowed 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. ā€œSo, 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 ā€œdidn't define what ā€˜activeā€™ means ā€”Ā is it just a relapse, or is it MRI disease activity?"Ā  For many clinicians, ā€œactiveā€ 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 ā€œobviously, 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. ā€œI 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 wonā€™t pose too much of an obstacle for patients, especially those with SPMS. ā€œI 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.

#ACTRIMS2019 ā€“ Jeffrey Cohen, MD, is New President of ACTRIMS

Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and ResearchĀ at the Cleveland Clinic, is the newly named Ā president of ACTRIMS, the Americas Committee for Treatment and Research in Multiple Sclerosis. Cohen’s appointment concluded the 2019 ACTRIMS ForumĀ that ran…

#ECTRIMS2018 – Ocrevus Used Early in MS Course Key to Slowing Disability, Genentech Director Says

Treating patients withĀ primary progressive or relapsing multiple sclerosis (MS) early with Ocrevus (ocrelizumab) is key to slowing disease progression, according to Hideki Garren, global head of Multiple Sclerosis and Neuroimmunology at Genentech. In an interview withĀ Multiple Sclerosis NewsĀ TodayĀ at the recentĀ 34thĀ congress of the European Committee for Treatment…

#ECTRIMS2018 – Finding Best Treatment for ‘Right Patient’ and Progressive MS Among Work of Interest, Cleveland Clinic Doctors Say

Tailored, highly effective therapies early in the disease’s course may be a way forward in multiple sclerosis (MS)Ā treatment, according to Cleveland Clinic neurologist Robert Bermel. Another neurologist with the Cleveland Clinic,Ā Robert Fox, talked about potential and upcoming progressive MS treatments.Ā  In interviews with Multiple Sclerosis News…

Ibudilast Slows Brain Shrinkage 48% in Progressive MS Patients in Phase 2 Trial; Lead Researcher Says Finding is ‘Remarkable’

Progressive multiple sclerosis patients ā€” with primary or secondary progressive disease ā€” treated with high doses of oralĀ ibudilastĀ in a Phase 2 clinical trial showed a 48 percent slowing in the progression of brain atrophy, or shrinkage, relative to those given a placebo, study data show. What this…

5 MS Patients Across US Talk About How Ocrevus Has Changed Their Lives

Itā€™s been a little over a year since U.S. regulators approved Genentechā€™sĀ Ocrevus (ocrelizumab)Ā as the first treatment for both relapsing and progressive forms of multiple sclerosis (MS) ā€” a disabling neurological diseaseĀ now believed to affect nearly one million Americans. While the juryā€™s still outĀ regarding the therapyā€™s…

Ocrevus a Year After Approval: Views of Some MS Experts

A year after U.S. regulators approved Genentech’sĀ Ocrevus (ocrelizumab)Ā as the first treatment for both the relapsing and progressive forms of multiple sclerosis, a prominent neurologist involved in the Phase 3 clinical trials that led to its authorization says it has been beneficial for some MS patients. But itā€™s simply…

New Ocrevus Data, Post-FDA Approval, Supports Range of Benefits, Genentech’s Hideki Garren Says

OcrevusĀ (ocrelizumab), Genentechā€™sĀ humanized anti-CD20 monoclonal antibody, continues to show clear evidence that it helps to slow disease progression and enable better function ā€” including in the hands and limbs ā€” ofĀ relapsing multiple sclerosis (MS)Ā and primary progressive multiple sclerosis (PPMS), latest data reveals. TheĀ first FDA-approved therapy ā€” in March…