The Axon – Issue #7, October 2024

Welcome to The Axon! If this is your first time reading this newsletter, welcome! If not, welcome back—feel free to continue ahead.

For those who aren't familiar with NeurologyLive, we're a team of editors who aim to bring busy clinicians, researchers, and investigators the latest news of neurology-related FDA actions and the therapeutic pipeline, in-clinic care and advocacy topics, and major medical meetings throughout the year, all wrapped up with expert opinions and insights on practice-relevant information. Our mission is to deliver?quality and relevant information to?health care professionals treating neurological diseases to help them achieve the best patient care possible. This newsletter is The Axon, your new go-to place to get that insight, right here on LinkedIn.

On the morning of the first of each month, we'll bring you a new edition to highlight the trending topics and important updates our editorial staff reports on. Without further ado, let's get into what happened this past month!

MDS Congress

We noted in last month's newsletter that the International Parkinson and Movement Disorder Society Congress was still wrapping things up in Philadelphia, Pennsylvania, as September came to a close. As a result, it was our launching point for October! We spent a few days in Philly speaking with trial investigators and industry scientists to find out what the latest therapeutic developments have been for movement disorders.

One of those conversations was with Daniel Claassen , MD, MS, a professor of neurology and chief of the Behavioral and Cognitive Neurology Division at Vanderbilt University Medical Center . He?shared his insight on the phase 1/2 data for ATH434, an investigational drug in development from Alterity Therapeutics designed to treat multiple system atrophy (MSA). Claassen dove into the therapy's mechanism of action and the currently known safety profile and considerations for its use, as well as the next steps in advancing care for patients with MSA as a whole, a discussion we featured in one of the latest episodes of our podcast, Mind Moments. Check it out here:

Additionally, another of our intriguing conversations—highlighted as part of our NeuroVoices weekly Q&A series—was with Lucia Ricciardi, MD, PhD, a consultant neurologist and senior lecturer at St. George's Hospital in London, United Kingdom, about a topic we've covered extensively this year: secondary symptoms of Parkinson disease. Ricciardi, whose work has focused on the biological, behavioral, and psychological experiences of nonmotor symptoms in patients with PD and other movement disorders, discussed the clinical manifestations of these symptoms, highlighting ways clinicians can identify and manage them.

The attention given to these symptoms is of utmost importance, especially as novel formulations of levodopa products continue to improve the ability to clinically manage motor symptoms. These symptoms continue to negatively affect patient quality of life, and they can be complex to address and caused by disease-related factors, medication-related factors, and social factors. In Ricciardi's words, "Neuropsychiatric symptoms have received more attention over the last 10 years, and many are interested in the topic now; however, these symptoms are still often overlooked in clinical settings. Although we are making progress, we’re still not doing enough."

Read the full conversation with Ricciardi here: NeuroVoices: Lucia Ricciardi, MD, PhD, on Addressing Neuropsychiatric Symptom Management in Parkinson Disease

Create an account for free to our feature story for more on this topic: Understanding the Significant Role of Secondary Symptoms of Parkinson Disease

Additionally, while in Philadelphia, we spent time chatting with a number of other stakeholders in the management of movement disorders, including:

• David Devos , MD, PhD, a neurologist and pharmacologist at CHU de Lille of Lille University, as well as cofounder of InBrain Pharma , who presented study findings on a device-assisted therapy that delivers dopamine directly to the brain, and its potential for treating PD. >>>WATCH: Potential of Device-Assisted Therapy for Advanced-Stage Parkinson Disease: David Devos, MD, PhD
• Amit Rakhit, MD, MBA , chief medical officer and chief development officer at BlueRock Therapeutics , who discussed the newly presented 24-month data from the phase 1 exPDite trial assessing bemdaneprocel in patients with PD, the design of the trial, the safety of the cell therapy, and some of the encouraging efficacy trends observed. >>>WATCH: Potential of Device-Assisted Therapy for Advanced-Stage Parkinson Disease: David Devos, MD, PhD

For more, check out all the news here: MDS 2024.

Expert Authors: Perspectives From the Clinic

October was a busy month for our clinician contributors and subject matter experts with all that's been happening in the field. There has been a lot to say!

To start, we were fortunate enough to work with one of our advisory board members and guest editor-in-chief Nina Riggins , MD, PhD, who helped oversee our fall newsletter of clinician-authored pieces. In her letter from the editor, she offered a look into the American Academy of Neurology 's Palatucci Advocacy Leadership Forum (PALF) and her PALF project: Anticipatory Pediatric to Adult Transition Program for Patients With Headaches. She and her team developed a checklist for pediatricians, neurologists, and any clinicians who treat teenagers with migraine.

Read her full letter here: Letter From the Editor – Fall 2024

Additionally, the newsletter issue included 3 other features that covered some topics of interest to practicing physicians in various subspecialties, including the following:

Challenges and Opportunities Bringing Lecanemab to Neurology Community Clinics, by Jose Soria, MD; Olena Bueno, RN; Uriel Romero, MD; Claudia Asencio, MA; Kevin McGehrin, MD; Branko Huisa, MD

• A group of experts from The Neuron Clinic shared their experience developing a novel inclusive clinical program to treat patients with early Alzheimer disease using lecanemab.

A Provider's Cheat Sheet Guide to Understanding Sleep, by Joanna Fong-Isariyawongse, MD , FAAN, FAES

• Sleep is critical for physical and mental health, with its insufficiency leading to various disorders and increased health risks; thus, clinicians should integrate sleep assessments and hygiene strategies into their clinical care.

College Checklist for People Living With Migraine, by Aishwarya Taneja , MD, FAAP

• Transition to college life poses unique challenges for students living with migraine, and a comprehensive checklist helps ensure they are prepared for this critical phase.

Unwinding Histone Deacetylase Inhibitors: Givinostat in Duchenne Muscular Dystrophy, by Kevin Chang, PharmD

• Amifampridine enhances neuromuscular transmission and relieves muscle weakness, showing promise for Lambert-Eaton myasthenic syndrome and other neuromuscular junction disorders.

Additionally, October featured a number of other submissions and op-eds on our site, including the latest from our consistent contributor Neal K. Shah , whose latest column dove into the ongoing changes to Medicare amid the ongoing boom in neurological disease—which is now one of the leading causes of long term care for the elderly and among the biggest contributors to global disease burden. As Shah puts it, "our current system isn't equipped to handle this surge. Family caregivers—often untrained and unsupported—are bearing the brunt of this crisis. They're providing 36 billion hours of unpaid care annually, often at great personal and financial cost."

But importantly, he highlighted 2 recent changes that could make an impact: the recently launched Medicare GUIDE program and the proposal for Medicare at Home.

Read more from Shah here: How America's Neurological Care Crisis is Reshaping Medicare and What That Means for You

While we were on-site at the 2024 ECTRIMS Congress—and in recent years at most multiple sclerosis (MS) focused meetings—we spoke a lot about the importance of addressing cognitive challenges in MS care. That starts with proper monitoring of cognition. In a recent article, Tom Fuchs , MD, PhD, of Amsterdam UMC , highlighted 3 types of tools that are often used to direct treatment: predictions, disease monitoring, and tailored treatment protocols, ultimately providing a clinician’s guide to using a personalized medicine approach to monitor cognition in MS.

Read more from Fuchs here: Holistic Personalized Care for Patients With Multiple Sclerosis and the Importance of Cognitive Monitoring

Another major story this month was another ripple out of ECTRIMS that we highlighted last month: the 2024 revisions to the McDonald criteria for the diagnosis of MS. Possibly the largest change to the criteria since they were first published in the early 2000s, these updates look to provide more tools for clinicians to utilize in diagnosis and to better consider the improved understanding of MS's pathology.

Daniel Ontaneda , MD, PhD, an associate professor of neurology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and a staff neurologist, at the Mellen Center for Multiple Sclerosis Treatment and Research at Cleveland Clinic ; and Jeffrey Cohen, MD, the director of the Experimental Therapeutics Program at Cleveland Clinic, noted in their recent piece that as the McDonald diagnostic criteria have evolved to meet the need for earlier detection, the field has faced challenges in increasing the sensitivity of the criteria without compromising specificity.

They wrote, "Addressing the current limitations of the McDonald diagnostic criteria remains an ongoing process in our quest to improve diagnostic speed, accuracy, and long-term patient outcomes. The 2024 revisions presented at the 40th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis mark a pivotal shift toward increased specificity through the addition of pathologically-specific biomarkers and expanding who can be diagnosed with MS. The 2024 revisions include some of the most substantial and paradigm-changing features since the inception of MS diagnostic criteria in 2001."

Read their full contribution here: Revised McDonald Diagnostic Criteria Signals New Era in Multiple Sclerosis Treatment

Ontaneda also appeared on an episode of Mind Moments to talk about the updates to the criteria, including a walkthrough of the specific additions of new biomarkers and the unanswered questions and challenges that still need attention. You can check out that conversation below:

Sleep Guideline Updates

In addition to the McDonald criteria's updates happening in MS, the field of sleep medicine also saw major changes to guideline documents in October, with a task force of experts in sleep medicine commissioned by the American Academy of Sleep Medicine (AASM) recently publishing new clinical practice recommendations for the treatment of restless legs syndrome, or RLS, in adults and pediatric patients.

Shortly after the publication, lead author John Winkelman , MD, PhD, the chair of the AASM committee and the chief of the Sleep Disorders Clinical Research Program at Harvard Medical School and Massachusetts General Hospital , sat with us to discuss the newly revised guidelines. During the conversation, he talked about the major risks associated with the long-term use of dopamine agonists for treating RLS. He also spoke about how alpha-2-delta calcium channel ligands compare with dopamine agonists in managing RLS symptoms. Furthermore, Winkelman explained the role of iron deficiency in RLS, and how these newer guidelines recommend addressing it for clinicians. Check that out below:

You can read the full treatment guidelines paper here:

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline

AANEM Annual Meeting

Even with everything going on this month in the news, we still found time to head down to Savannah, Georgia, for the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting to connect with physicians, technologists, and other healthcare professionals working in neuromuscular, musculoskeletal, and electrodiagnostic medicine. While down south, we covered a number of data presentations from the conference, including data on the investigational agent nipocalimab, , which demonstrated efficacy and safety in an adolescent population of myasthenia gravis; data on subcutaneous efgartigimod PH20, which proved efficacious in previously treated patients with chronic inflammatory demyelinating polyneuropathy; data on a ranging cycle cadence of rozanolixizumab treatment, which suggested a need for an individualized approach; as well as looks at upcoming trials in myasthenia gravis of combination pozelimab and cemdisiran, the bispecific nanoanitbody gefurulimab, and IV efgartigimod in seronegative disease.

One of our conversations was around the Lambert Lecture, which addressed the challenges and opportunities of adapting medical education in a digital age. The talk was given by Lawrence Robinson, MD, the senior scientist at Sunnybrook Research Institute, and he gave us a summary of his plenary lecture at the meeting. He discussed the shift of technological advancement in medical education, especially its role in fostering critical thinking and managing the vast influx of information. Check out that conversation below:

We also spoke with, among many others:

• Henry Kaminski , MD, the Meta A. Neumann Professor of Neurology at George Washington University, who provided an overview of a new phase 3 study, called MyClad, testing the efficacy and safety of cladribine versus placebo in generalized myasthenia gravis. >>>WATCH: Innovative MyClad Study Testing Cladribine Capsules in Generalized Myasthenia Gravis
• Richard Nowak, MD, MS , the director of the myasthenia gravis clinic at 耶鲁大学 , who provided clinical insight on promising phase 3 data assessing inebilizumab, an FDA-approved therapy for NMOSD, in patients with myasthenia gravis. >>>WATCH: Understanding the Therapeutic Potential of Inebilizumab in Myasthenia Gravis
• Christopher Scheiner, MD, PhD, a neuromuscular specialist at the UT Medical Center provided clinical insight on a retrospective analysis studying the long-term corticosteroid patterns of approved treatments for generalized myasthenia gravis. >>>WATCH: Therapeutic Benefits of Steroid-Sparing Effect From New Myasthenia Gravis Medications
• Rachana K. Gandhi Mehta, MBBS, an assistant professor of neurology at Wake Forest University School of Medicine , who provided clinical insight on MG0020, a phase 3 trial assessing a self-administration of rozanolixizumab through a syringe driver. >>>WATCH: Therapeutic Potential of Self-Administered Subcutaneous Rozanolixizumab in Myasthenia Gravis
• Judith Thompson, PhD, the rare disease population health strategy lead at 优时比 , who provided clinical insight on some of the unique challenges of diagnosing myasthenia gravis, and some of the early signs clinicians and non-specialists should look for. >>>WATCH: Identifying Small Clinical Characteristics to Facilitate Early Myasthenia Gravis Diagnosis

Long COVID Clinical Care

In addition to last month's team-up with our sister site and infectious disease publication Contagion_Live to produce the feature article on long COVID (read here: Beyond the Virus: Long COVID’s Neurological Toll), our teams also came together in collaboration with a group of clinicians to host a long-form discussion about the state of treatment for this not-so-understood condition. That group included Ravindra Ganesh, MD, MBBS, FACP, Dip ABOM ; Svetlana Blitshteyn, MD, FAAN; and Monica Verduzco-Gutierrez, M.D.

You can check out the full series here: A Deep Dive: Understanding the Neurological Toll of Long COVID

FDA News Timeline

As we always are, the team spent a good portion of our month tracking pipeline activity and decisions from the FDA. October was by no means a slow month, and a number of applications were submitted to the agency while we also tracked a pair of approvals in pediatric narcolepsy and advanced Parkinson disease.

October 7 — Neuvivo Submits NDA to FDA for Investigational ALS Treatment NP001

• If approved, NP001 could potentially be the first disease-modifying therapy that restores balance over uncontrolled inflammation in the body’s own innate immune system for ALS. In March 2023, Neuvivo announced that data from a phase 2 study published in Cells assessing NP001 showed that C-reactive protein (CRP) levels in patients with ALS correlated with lung function. Notably, plasma TGFB1, a dominant regulator of inflammation, was 95% higher after 6 months in high CRP-treated patients relative to controls, suggesting the therapy may have acted in part to reset the innate immune system.

October 9 — Capricor Submits BLA for Approval of Dermiocel in Treating DMD Cardiomyopathy

• The rolling submission is the first step toward full approval for the investigational agent deramiocel as a new treatment for patients with Duchenne muscular dystrophy cardiomyopathy. In the recent announcement, the company noted that it plans to complete its rolling BLA submission by the end of 2024. In September, Capricor Therapeutics, Inc. claimed it was using data from the phase 2 HOPE-2 (NCT03406780) and HOPE-2 open-label extension trials as supplementary evidence, as well as combined data from cohorts A and B of the phase 3 HOPE-3 trial (NCT05126758). Notably, the company does not intend to unblind Cohort A from HOPE-3 at this time, which was expected to occur in the fourth quarter of 2024.

October 17 — FDA Approves AbbVie’s 24-Hour Foscarbidopa/Foslevodopa Pump for Advanced Parkinson Disease Treatment

• AbbVie 's foscarbidopa/foslevodopa, marketed as Vyalev, is the first and only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced Parkinson disease (PD). The company noted that the timing for a patient's access to the therapy is dependent on their individual insurance plan, with coverage for Medicare patients expected in the second half of 2025. The approval was supported by data from the phase 3 M15-736 study (NCT04380142) that assessed the efficacy of continuous subcutaneous infusion of foscarbidopa/foslevodopa (also known as ABBV-951) among adult patients with advanced PD compared with oral immediate-release carbidopa/levodopa (CD/LD IR), along with a 52-week, open-label M15-741 study (NCT03781167) which investigated the long-term safety and efficacy of the treatment. Results from the M15-736 study revealed that patients who received foscarbidopa/foslevodopa reported superior improvement in motor fluctuations, with increased ON time without troublesome dyskinesia and decreased OFF time, compared with oral CD/LD IR.

October 7 — FDA Approves Avadel's Sodium Oxybate for Cataplexy or Excessive Daytime Sleepiness in Pedatric Narcolepsy

• Avadel Pharmaceuticals PLC 's supplemental new drug application for sodium oxybate (Lumryz) was approved for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. With this approval, the therapy could reduce the burden on families and caregivers of pediatric patients with narcolepsy who must wake up at night to administer a second dose. The initial approval was supported by data from the phase 3 REST-ON trial (NCT02720744), which was held under a special protocol assessment agreement with the FDA. The study featured 222 patients with narcolepsy type 1 or 2, all aged 16 years or older, who received uptitration doses of 4.5 g, 6 g, 7.5 g, and 9 g of Lumryz or placebo over the course of a 3-week screening period, 13-week treatment period, and 1-week follow-up period. All told, the study met all 3 of its primary end points of change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression Improvement, and weekly cataplexy attacks within the 6-, 7.5-, and 9-g groups.
• Following the approval for sodium oxybate, we sat down with Anne Marie Morse , DO, FAASM, a pediatric sleep disorders expert who is the director of Child Neurology and Pediatric Sleep Medicine at Geisinger 's Janet Weis Children's Hospital, for a special episode of Mind Moments in which she offered commentary on the clinical considerations behind this once-nightly formulation of sodium oxybate, and how it should be used going forward. Check that out here:

CTAD 2024

The final days of October were spent with our team heading across the Atlantic to Madrid, Spain, for the annual Clinical Trials on Alzheimer's Disease Conference. The field of dementia, and specifically Alzheimer, has been full of updates and new clinical developments over the past 5 years, with huge strides being taken in research and treatment development.

Thus far, just some of the many experts we'll be posting interview clips of from the meeting include:

• Howard Fillit, MD , the chief science officer of the Alzheimer's Drug Discovery Foundation
• Margherita Carboni , PhD, the indication lead for neurology at Roche Diagnostics USA
• Sandi See Tai , MD, the chief development officer at Lexeo Therapeutics
• Kimberly Johnson , MD, the division chief of memory disorders at 美国杜克大学
• Ralph Kern , MD, MHSc, the chief medical officer at Cognito Therapeutics, Inc.

While in Madrid, we covered a number of major updates from ongoing trials, including new data from a placebo-controlled phase 2 trial (NCT05081219) showed that a combination treatment approach with intranasal insulin (INI) and empagliflozin (empa), which had positive effects on cognition and several other immune/inflammatory biomarkers in patients with mild cognitive impairment (MCI) or early Alzheimer disease (AD), and overall support the continued investigation of this combination method for AD.

We also covered the announcement of the trial design of a phase 3 study assessing remternetug ( 礼来 ), which should begin enrollment in October 2024 to test the effects of the agent, an IgG1 monoclonal antibody directed at deposited brain amyloid plaque; and data from the phase 2 Autonomy trial (NCT04619420), a study assessing an anti-phosphorylated tau agent posdinemab ( The Janssen Pharmaceutical Companies of Johnson & Johnson ) in early AD, and the first to employ a plasma biomarker as a prescreening tool. Baseline tau PET standardized uptake value ratio was linked to clinical outcomes across multiple brain areas, especially impacting immediate memory, language, and delayed memory in that trial.

The team was also on top of data on therapies, namely from the phase 3b TRAILBLAZER-ALZ-6 trial (NCT05738486), a study of the recently approved antiamyloid treatment donanemab (Kisulna; Eli Lilly), that showed that an enhanced titration dosing regimen of the treatment led to significant reductions in the frequency and severity of amyloid-related imaging abnormalities-edema (ARIA-E). In addition to numerically lower ARIA-E at 24 weeks, those on the titrated dosing regimen also maintained sufficient amyloid reduction. Additonally, there was new data from E2814-G000-103, an open-label, phase 1b/2 study (NCT04971733) of patients with dominantly inherited AD that showed that treatment with E2814 ( 卫材 ), an investigational anti-tau therapeutic antibody, resulted in significant effect on both early and late tau biomarkers in treated patients. Notably, E2814 did not affect phosphorylated tau217 or MTBR-tau243 levels in healthy volunteers, suggesting its effects are specific to those with tau pathology and thus further supporting its clinical development.

The meeting is still going on as of today, November 1, so we'll be providing more updates on our website in the coming week—and we'll likely sneak some into next month's newsletter. But, if you can't wait, you can check in on all of our coverage here: CTAD 2024.

That wraps up this month's issue of The Axon—thanks for reading! Remember to subscribe to get alerts each time a new issue goes live!

Do you have a lead on a story you want to share? Let us know by emailing Matt Hoffman, our editorial director, at [email protected].

We'll see you here next month!