NeurologyLive Staff

This week Neurology News Network covered the phase 2b/3 study evaluating blarcamesine in patients with Alzheimer disease, the effect of higher nusinersen levels on outcomes in patients with spinal muscular atrophy, and data from the MONEAD study which evaluated the neurodevelopment of children of women with epilepsy taking antiseizure medications. 

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the 

team, moves to working remote as we come together to help reduce the spread of the novel coronavirus.

Anavex Life Sciences recently announced that it has 

 of 450 patients for its ongoing phase 2b/3 study evaluating its investigational agent blarcamesine, formerly known as ANAVEX 2-73, in patients with Alzheimer disease (AD). Topline results from the study are expected to be announced by mid-2022. The double-blind, placebo-controlled 48-week clinical study is using the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) and Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) subscales as primary end points to assess the cognitive and functional efficacy of blarcamesine. Patients included in the study will be randomized 1:1:1 to 2 different blarcamesine doses or placebo. Blarcamesine, an orally available investigational agent, will also be evaluated on SIGMAR1 gene expression, a prespecified precision medicine biomarker. This gene expression correlated with direct measures of clinical benefit, cognition, and activities of daily living and function in the previously completed phase 2a study, the first genome-wide search for biomarkers associated with therapeutic response in AD.

Analysis presented at the 2021 Cure SMA Research & Clinical Care Meeting, showed that higher nusinersen (Spinraza; Biogen) levels are 

 of plasma pNF-H levels in patients with spinal muscular atrophy (SMA) and may lead to clinically meaningful improvement in motor function beyond that observed with the approved 12 mg dose. The pharmacokinetic/pharmacodynamic (PK/PD) model indicated that patients exposed to higher nusinersen cerebrospinal fluid (CSF) were correlated with greater efficacy, as measured by change from baseline in Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores. Furthermore, exposure levels also predicted clinically meaningful increases of at least 5 points on CHOP INTEND. Nusinersen, an antisense oligonucleotide administered intrathecally, received FDA approval for the treatment of children and adults with SMA in December 2016. Since its approval, the drug has had a multitude of studies conducted to further confirm its efficacy and safety in this patient population.

Data from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study showed that children of women with epilepsy (WWE) taking antiseizure medications (ASMs) 

did not differ in neurodevelopmental outcomes

 compared to those of healthy women. Overall, investigators found no significant differences between children of WWE vs healthy women for the primary language domain outcome. In the full model, significant factors such as higher maternal IQ, birth weight, and female child sex were associated with higher language domain scores. The study authors wrote, “This encouraging finding may be due to the use of newer ASMs with lower risk of affecting the immature brain. However, these findings must be interpreted within the context that neuropsychological assessments conducted at 2 years of age are not as strongly associated with adolescent/adult functioning as assessments performed in older children, which will be conducted subsequently in the MONEAD study.”

For more direct access to expert insight, head to NeurologyLive.com. This has been Neurology News Network. Thanks for watching.

Videos

Neurology News Network for the week ending June 19, 2021. 

Blarcamesine Exceeds Enrollment, Higher Plasma Nusinersen Leads to Meaningful Improvements, Neurodevelopmental Outcomes Unchanged by Maternal ASMs

's Friday 5! Every week, the staff compiles 5 highlights of 

's widespread coverage in neurology, ranging from newsworthy study findings and FDA action to expert interviews and peer-to-peer panel discussions.

 Impact of the Approval of Aducanumab on the Treatment Landscape in Alzheimer Disease

Alzheimer disease experts Richard S. Isaacson, MD, and Marc E. Agronin, MD, discuss the impact of the approval of aducanumab on the treatment landscape and other drugs in development for the treatment of Alzheimer disease.

 MRI in Multiple Sclerosis Guidelines Update: North America, Europe Align on New Recommendations 

These consensus guidelines are significant not only for their key updates to clinical practice but for their representation of a more unified, global approach to diagnosing and monitoring patients with multiple sclerosis. They were developed by the MAGNIMS, CMSC, and NAIMS groups.

 NeuroVoices: Michael J. Thorpy, MD, on FT218, State of Current Sleep Care

The director of the Sleep-Wake Disorders Center at Montefiore Medical Center detailed the overall state of sleep care and the advantages the investigational narcolepsy drug FT218 brings to the growing pipeline of therapies and other topics from 

 Peer Exchange: Managing Patient/Parent Expectations in Dravet

Joseph Sullivan, MD; Trevor J. Resnick, MD; Elizabeth A. Thiele MD, PhD; and Elaine C. Wirrell, MD, engage in a

discussion on having conversations with the parents of patients with Dravet syndrome with regards to adjustments to therapy and managing their expectations.

 Holding On to Hope in Huntington Disease

Daniel O. Claassen, MD, MS, details that despite a few surprising program failures early this year from Roche and Wave Life Sciences, there is plenty of potential worth holding on to in the Huntington disease pipeline.

If you missed your chance to see the June broadcast of our free webinar series, "The Ever-Changing Face of Multiple Sclerosis," put on in partnership with the Consortium of Multiple Sclerosis Centers, don't fret! You can join Ahmed Obeidat, MD, PhD; Anne Cross, MD; and Gloria von Geldern, MD, and others as they discuss the evolution of therapeutics for the treatment of multiple sclerosis. 

To view the enduring version of either of the first 3 programs, 

 for our Future Leaders in Neurology section. 

Articles

Take 5 minutes to catch up on NeurologyLive's highlights from the week ending June 18, 2021.

NeurologyLive Friday 5 — June 18, 2021

This week Neurology News Network covered a number of presentations at the 2021 American Headache Society 63rd Scientific Annual Meeting, including findings that show clinically meaningful improvements from telemedicine, the lack of wearing off effect from galcanezumab, and the relative efficacy of ubrogepant compared to other CGRPs. 

team, moves to working remote as we come together to help reduce the spread of the novel coronavirus. This week’s episode is centered around the 2021 American Headache Society 63rd Scientific Annual Meeting.

Using a retrospective review that assessed Headache Impact Test-6 (HIT-6) scores over a year-long period, researchers concluded that 

clinically meaningful improvement in migraine

 can be achieved with the exclusive use of synchronous video telemedicine visits for migraine care. Brad Torphy and colleagues evaluated the use of synchronous video telemedicine in the management of migraine from the initial visit onward for 73 patients who had a telemedicine visit from March 3, 2020, to March 18, 2021. When comparing initial and follow-up HIT-6 assessment scores, researchers recorded a 6-point change. An improvement in HIT-6 score was observed in 80% of patients who met screening criteria at follow-up. Notably, 60% of those patients with improvement had a reduction of at least 6 points or more, which the authors noted met a threshold that was previously identified as clinically meaningful in patients with chronic migraine.

Recent data from a post-hoc analysis of several studies of 

 suggest that rates of individual patients meeting the threshold of “wearing off” of treatment efficacy were low with no statistically significant differences observed among placebo and galcanezumab dose groups. Ailani and colleagues analyzed individual patient-level data from 4 double-blind, placebo-controlled phase 3 studies: EVOLVE-1 and EVOLVE-2 of high frequency episodic migraine (EM), REGAIN of chronic migraine (CM), and CONQUER of CM and EM. The investigators found that rates of wearing off in EM populations were comparable among placebo and galcanezumab-treated patients, with 4% to 7% of patients meeting the predefined criteria. In the EVOLVE trials, in which 3 months of data were available, less than 1% of patients met the criteria during all 3 months.

systematic literature review evaluating the relative efficacy

 of rimegepant (Nurtec ODT; Biohaven), atogepant (Allergan), and monoclonal antibody (mAb) treatments for the prevention of migraine showed generally similar effects when compared to each other.Overall, all of the treatments observed showed significantly favorable differences compared to placebo for both change in MMDs and number achieving at least a 50% reduction in baseline MMDs. Results for change in MMDs vs placebo ranged in magnitude from eptinezumab 100 mg to galcanezumab 240 mg while rimegepant had a difference vs placebo of -0.90. Atogepant 60 mg daily represented the lowest risk difference estimate vs placebo for achieving at least a 50% reduction in baseline MMDs, while the magnitude reached the greatest for galcanezumab 120 mg (23.40%). Rimegepant had a difference vs placebo of 12.90%.

Neurology News Network for the week ending June 12, 2021. 

Telemedicine Produces Meaningful Migraine Improvement, Galcanezumab Shows No Wearing Effect, CGRPs All Significant Improve MMDs

 It's Complicated: Why Aducanumab's Approval Raises More Questions Than Answers

Alzheimer disease experts Richard S. Isaacson, MD, and Marc E. Agronin, MD, discuss the recent aducanumab approval and some of the clinical community's concerns.

 Mind Moments Ep. 39: A Controversial FDA Decision 

, brings you an exclusive interview with a number of experts in Alzheimer disease to gauge their reaction to the controversial FDA decision to approve aducanumab (Aduhelm; Biogen) and the potential impact that this first approval since 2003 may have on research, policy, and treatment.

 NeuroVoices: Andrew Blumenfeld, MD, on a Combination Approach to Treating Chronic Migraine

The director for the Headache Center of Southern California discussed his research presented at the 

American Headache Society's 2021 Annual Scientific Meeting

, which evaluated a combination of onabotunlinumtoxinA and calcitonin gene-related peptide targeting agents in patients with chronic migraine.

 Importance of Early Diagnosis for Dravet Syndrome

Redefining Treatment Outcomes in Dravet Syndrome

," Joseph Sullivan, MD; Trevor J. Resnick, MD; Elizabeth A. Thiele MD, PhD; and Elaine C. Wirrell, MD, offer panelists discuss recommendations for the diagnosis, treatment, and management of patients with the rare epilepsy syndrome.

 Best Practices for Patient Compliance in Epilepsy Treatment

In this segment of the Insights series, "

Patient Compliance with Treatments for Epilepsy

," Imad Michel Najm, MD, discusses various factors to consider when diagnosing epilepsy in patients, such as when to start drug therapy as well as patient resistance to medications, and shares his best practices for improving compliance.

If you missed your chance to see the May broadcast of our free webinar series, "The Ever-Changing Face of Multiple Sclerosis," put on in partnership with the Consortium of Multiple Sclerosis Centers, don't fret! You can join Ahmed Obeidat, MD, PhD; Mitch Freedman, MD; and Suma Shah, MD, and others as they discuss the evolution of therapeutics for the treatment of multiple sclerosis. Additionally, you can register for the live broadcast of the third installment on June 16, 2021, for a detailed discussion on the evolution of diagnosis and treating multiple sclerosis care during a pandemic featuring Obeidat; Anne Cross, MD; and Gloria von Geldern, MD.

To register for the next broadcast for free, 

To view the enduring version of either of the first two programs, 

Take 5 minutes to catch up on NeurologyLive's highlights from the week ending June 11, 2021.

NeurologyLive Staff

Articles

Blarcamesine Exceeds Enrollment, Higher Plasma Nusinersen Leads to Meaningful Improvements, Neurodevelopmental Outcomes Unchanged by Maternal ASMs

NeurologyLive Friday 5 — June 18, 2021

Telemedicine Produces Meaningful Migraine Improvement, Galcanezumab Shows No Wearing Effect, CGRPs All Significant Improve MMDs

NeurologyLive Friday 5 — June 11, 2021