Jeff Guptill, MD, Neuromuscular Clinical Development Lead at Argenx, discusses the impact of the Vyvgart (efgartigimod alfa) approval on the myasthenia gravis (MG) community to treat patients with anti-MuSK-Ab positive, anti-LRP4-Ab positive, and/or triple seronegative MG.

MG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

In May 2026, the US Food and Drug Administration (FDA) approved Vyvgart (efgartigimod alfa) and Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase) for the treatment of adult patients who have anti-MuSK-Ab positive, anti-LRP4-Ab positive, and/or triple seronegative MG. The medication was previously approved to treat patients with anti-AChR-Ab positive gMG.

Efgartigimod alfa is a first-in-class human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG autoantibodies. Vyvgart Hytrulo is a subcutaneous combination of efgartigimod alfa and recombinant human hyaluronidase PH20 (rHuPH20) that allows for subcutaneous injection delivery.

Until this approval, traditional therapy was limited to cholinesterase inhibitors, corticosteroids and immunosuppressants for these MG subpopulations. However, research has shown that these subpopulations react to treatments in different ways, highlighting the need for more treatment options and research aimed at these specific subgroups.

Dr. Guptill explains the importance of this approval, specifically for the triple seronegative patients who now have their first rigorously studied treatment with a favorable safety and efficacy profile.

For more information on this approval visit, https://checkrare.com/fda-expands-indication-of-vyvgart-efgartigimod-alfa-for-adults-with-seronegative-myasthenia-gravis/

CHAPTERS
Introduction 00:00
Vyvgart (Efgartigimod Alfa) Indication 00:17
Antibody Presence’s Impact on Symptoms 00:47
Standard Therapy for Nontraditional Patients 1:52
Importance of Treatment Options 3:08
What Physicians Should Know 4:04

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Kerrie-Anne Ho, PhD, Patient Preference Lead at UCB, discusses preferences and perceptions of acute seizure medications.

Data from interviews with people with seizures (PwS) and caregiver interviews were presented at the American Academy of Neurology (AAN) 2026 Annual Meeting.

Patient and Caregiver Perceptions of Acute Seizure Medications and the Rapid and Early Seizure Termination (REST) Approach: Qualitative Interviews

The objective of this study was to assess understanding of the awareness of the Rapid and Early Seizure Termination (REST) paradigm and perceptions around acute (on-demand) medications among PwE and caregivers. REST is essential in preventing seizures from becoming prolonged seizures and progressing in severity.

A total of 53 participants (18 PwE, 35 caregivers) participated in 60-90-minute qualitative interviews regarding experiences with auras/epilepsy concepts/experience and unmet needs of acute medications/perceptions of REST. Of 44 participants who reported experiencing auras, 68% were extremely/very confident that they could predict a seizure from auras. The most frequent description of prolonged seizures given was longer than 5 minutes. Only 13% of participants did not use/administer benzodiazepines as acute medication for prolonged seizures. Regarding acute medication, 36% of participants desired to change the mode of administration and 23% wanted improved effectiveness.

53% of respondents perceived REST medication as quick/fast if it acts within the first minute of the seizure and 15% were aware of the REST concept. Of 45 participants not currently following the REST approach, 67% perceived REST to be feasible.

Patient and Caregiver Preferences for Acute Seizure Medications: A Quantitative Survey

The objective of this study was to explore the preferences of PwE and caregivers on attributes of acute (on-demand) seizure medications.

PwE aged 18 years and older who had experienced 1 or more prolonged seizures of 2 minutes or longer in the past 12 months and caregivers of PwE aged 12 years and older were included in the survey.

A total of 135 adult PwE and 239 caregivers participated (n=374). Overall, 46% of participants reported generalized or bilateral/tonic-clonic as their most common seizure type, 52% reported 3-5 seizures/month on average, and 57% reported an average duration of 1 to 4 minutes for the most common seizure type over the past 12 months. 57% of participants reported using oral acute medication for prolonged seizures.

The survey noted that all attributes significantly influenced treatment preferences, with the most important being time to seizure cessation and mode of administration. Nasal spray and single-use inhaler were most preferred, whereas rectal was least preferred. Participants preferred treating early in the seizure and faster-acting medications. Willingness-to-wait exercise showed that 88% of participants would be willing to wait 30 seconds (the minimum time proposed) to administer acute seizure medication.

CHAPTERS
Introduction 00:00
The REST Paradigm 00:25
Abstracts Presented at AAN 1:42
Theory on Waiting for Medication Administration 5:19
Next Steps 6:02

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Abigail Schwaede, MD, Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine, discusses results on intravenous efgartigimod in juvenile generalized myasthenia gravis (gMG).

gMG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. It mostly develops in adults but children can also develop this rare condition. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

The ADAPT JR (NCT04833894) clinical trial is a phase 2/3, open-label, uncontrolled study evaluating the pharmacokinetics, pharmacodynamics, safety, and activity of efgartigimod in children ages 2 to 18 years of age with acetylcholine receptor antibody–positive (AChR-Ab+) gMG. Efgartigimod is a human immunoglobulin G1 antibody Fc fragment, which blocks the neonatal Fc receptor. Phase 3 ADAPT/ADAPT+ trials demonstrated that efgartigimod IV is efficacious and well tolerated in adults with gMG.

During dose-confirmatory part A, participants received 1 efgartigimod infusion and pharmacokinetic, pharmacodynamic, and safety endpoints were monitored over 8 weeks. During treatment response–confirmatory part B, participants received 1 or 2 cycles of 4 once-weekly efgartigimod infusionsand additional endpoints, including MG Activities of Daily Living (MG-ADL) scores, were assessed over 18 weeks.

In the adolescent cohort, 6 participants enrolled in part A and continued to part B, and 5 participants enrolled directly in part B. Efgartigimod treatment resulted in IgG and AChR-Ab decreases similar to those observed in previous studies of adults with gMG. Safety profile and MG-ADL improvements were also similar to previous observations.

ADAPT JR child cohort enrollment is ongoing.

CHAPTERS
Introduction 00:00
Juvenile-Onset Myasythenia Gravis 00:14
Antibody Presence in Juvenile Disease 2:59
ADAPT JR Clinical Trial 5:15
Next Steps 8:47

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Julia Scarisbrick, MD, MBhons, ChB, FRCP, is one of the leaders of the PROCLIPI (Prospective Cutaneous Lymphoma International Prognostic Index) study, a registry of patients with cutaneous T-cell lymphoma (CTCL). Dr. Scarisbrick, Professor of Dermatology, Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom, discusses the study’s objectives, as well as challenges in the diagnosis of CTCL.

Cutaneous T-cell lymphoma (CTCL) is a rare group of skin malignancies that includes aggressive (e.g., Sézary syndrome) and nonaggressive or indolent forms (e.g, mycosis fungoides). However, advanced mycosis fungoides can be a dangerous cutaneous lymphoma.

One of the most important unmet needs in patients with CTCL has been differentiating patients at high risk for poor outcomes from those at lower risk, which can directly affect treatment choices.
The PROCLIPI (Prospective Cutaneous Lymphoma International Prognostic Index) trial, an international registry study, sought to use years of prospectively collected patient data (from 552 patients with advanced stage mycosis fungoides or Sézary syndrome) to develop a prognostic index. An implication of a successful new prognostic index would be an improvement in the existing disease staging algorithm (IA–IVB) to better reflect survival rates.

The use of this new prognostic index will allow physicians to identify the subset of patients at high risk for poor outcomes, which would directly affect treatment decision making.

Another important unmet need in CTCL is improving diagnosis. At present, diagnosis of CTCL depends on a combination of clinical findings, skin biopsies, and genetic tests. A physician who is evaluating a skin lesion may not include CTCL in the differential diagnosis, and as a result, the diagnosis delay can be 3 years or more. A singular diagnostic test would be extremely helpful for family doctors and community dermatologists in considering CTCL as a potential cause and potentially improve the diagnostic yield in the community. The data from this repository of 10 years of patient data may help lead to this diagnostic simplification. Diagnostic delay can result, over time, in T-cell cancer affecting the lymph nodes, blood, and even visceral organs.

CHAPTERS
Introduction 00:00
PROCLIPI Registry Insights 00:19
Reducing Diagnostic Challenges 2:38
Early Skin Symptoms 3:47
Implications on Patient Care 5:21
Impact on Diagnosis, Risk Stratification, and Decision Making 6:16
Take Home Message 7:14

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Carolina Barnett-Tapia, MD, Neuromuscular Neurologist and the University of Toronto, discusses the safety and efficacy of subcutaneous efgartigimod PH20 in ocular myasthenia gravis (oMG).

oMG is a neuromuscular disease characterized by autoantibody production against post-synaptic proteins in the neuromuscular junction. oMG typically presents as almost exclusively ocular symptoms and can evolve into generalized myasthenia gravis (gMG) in about 20% to 60% of cases. Common ocular manifestations include fluctuating ptosis, diplopia, and orbicularis weakness.

The Phase 3 ADAPT OCULUS trial (NCT06558279) is a randomized, double-blind, placebo-controlled, parallel-group design study evaluating the efficacy and safety of efgartigimod PH20 subcutaneous administered by a prefilled syringe in adults with oMG. Efgartigimod PH20 is a human immunoglobulin G1 (IgG1) antibody Fc fragment coformulated with recombinant human hyaluronidase PH20 that selectively reduces IgG levels by blocking neonatal Fc receptor–mediated IgG recycling.

In Part A of this trial, adults with confirmed oMG and a Myasthenia Gravis Impairment Index (MGII) patient-reported outcome subcomponent ocular score of 6 or greater are randomized to receive 4 once-weekly efgartigimod PH20 1000 mg or placebo, followed by 4 weeks of follow-up.

The primary endpoint is change in MGII patient-reported outcome ocular score from baseline to week 4. Key secondary endpoints include changes from baseline to week 4 in MGII ocular score (patient-reported outcome plus physical examination) and MGII total score. Safety assessments include adverse event incidence and severity. Topline results highlighted that the primary endpoint was met.

CHAPTERS
Introduction 00:00
Ocular Myasthenia Gravis 00:13
Susceptibility of Ocular Manifestations 1:53
ADAPT OCULUS Clinical Trial 3:05
Access to Treatment 5:43
Patient Burden 6:48

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John Day, PhD, MD, Director of Neuromuscular Medicine at Stanford University, discusses the development of Itvisma gene therapy for patients with spinal muscular atrophy (SMA).

SMA is a group of genetic neuromuscular disorders that affect the motor neurons, causing progressive muscle weakness and loss of movement due to atrophy. Many types of SMA mainly affect the muscles involved in walking, sitting, arm movement, and head control. Breathing and swallowing may also become difficult as the disease progresses in many types of SMA. SMA type 1, 2, 3, and 4 are caused by mutations in the SMN1 gene. Extra copies of the nearby related gene, SMN2, modify the severity of SMA. There are other rarer types of SMA caused by changes in different genes.

In the last decade, there has been growing development in gene therapy for SMA. In 2017, an intravenous adeno-associated virus (AAV) vector-based gene therapy, Zolgensma (onasemnogene abeparvovec), was developed. Later approved in 2019, the therapy was indicated for patients less than 2 years of age with SMA due to weight-based dosing limitations. As Dr. Day explains, the treatment’s intravenous administration and large viral load caused concerns on reactions and side effects.

To address these limitations, researchers began the development of a spinal injection administration. Dr. Day explains how this allows for a more targeted approach that can be dosed in lower amounts, thus decreasing concerns on reactions.

Itvisma (onasemnogene abeparvovec), approved in November 2025, is a one-time intrathecal injection for patients with SMA. It is the first gene therapy licensed to be given via spinal injection, which Dr. Day highlights will change the landscape for other genetic central nervous system disorders.

The approval of Itvisma was based on data from the registrational phase 3 STEER clinical trial and supported by the open-label phase 3b STRENGTH study. Itvisma was observed to significantly improve motor function and stabilization of motor abilities typically not seen in the natural history of the disease, with effects sustained over 52 weeks of follow-up. Additionally, the safety profile of Itvisma was consistent across both studies. The most common adverse events in the STEER study were upper respiratory tract infection and pyrexia, and the most common adverse events in the STRENGTH study were common cold, pyrexia, and vomiting.

CHAPTERS
Introduction 00:00
SMA Overview 00:25
Current Management 1:46
The Development of Itvisma Gene Therapy 2:38
Status of Nerves at Treatment 7:06
Advice to Newly Diagnosed Families 10:37
Take Home Message 13:00

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Michael Levy, MD, PhD, Neuroimmunologist and Associate Professor at Harvard Medical School, discusses results from the METEOROID clinical trial of Enspryng (satralizumab) in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

MOGAD is a rare autoimmune condition characterized by antibodies attacking the central nervous system; specifically the MOG protein that makes up myelin in the optic nerves, brain, and spinal cord. Common symptoms include vision loss, pain, fatigue, numbness, muscle weakness and loss of coordination, and cognitive dysfunction. Currently, there are no approved treatment options available for MOGAD.

At the 2026 American Academy of Neurology (AAN) annual meeting, new data was presented from the METEOROID clinical trial. METEOROID is a phase 3, randomized, double-blind, placebo-controlled, multicenter study of satralizumab in adults and adolescents 12 years and older with MOGAD. Satralizumab is a humanized monoclonal antibody that targets interleukin-6 (IL-6) receptor activity designed to lower disease-related antibody production, suppress inflammatory T cells and restore the integrity of the blood-brain barrier.

The primary endpoint showed 87% of patients on satralizumab were relapse free, compared to 67% on placebo at 48 weeks. Onset of response was observed at as early as 8 weeks. A generally consistent efficacy was observed across subgroups, including age, sex, race and background therapy use. Satralizumab also reduced the annualized relapse rate (ARR) by 66%.

Satralizumab was also observed to have the potential to reduce central nervous system inflammation and use of rescue therapies such as steroids, plasma exchange or intravenous immunoglobulins. There was a 79% reduction in the annualized rate of active lesions on MRI across the optic nerves, brain and spinal cord and a 73% lower proportion of patients receiving rescue therapy compared to placebo. In addition, a 17% reduction in the annualized rate of inpatient hospitalizations was observed with satralizumab compared to placebo.

Additionally, no new safety signals were reported and the safety profile was consistent with established data. The most common adverse events included injection-related reactions, influenza, arthralgia, back pain, sinusitis, and diarrhea.

To learn more about MOGAD and other rare ophthalmology conditions, visit https://checkrare.com/diseases/ophthalmology-eye-diseases/

CHAPTERS
Introduction 00:00
NMOSD Versus MOGAD 00:14
Current Management 2:09
METEOROID Clinical Trial 3:51

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Sumaira Ahmed, Founder and Executive Director of The Sumaira Foundation, discusses her organization and the BEST-NMOSD clinical trial for patients with neuromyelitis optica spectrum disorder (NMOSD).

NMOSD is a rare autoimmune disorder that largely affects the spinal cord and optic nerves. Symptoms include pain, weakness, bowel and bladder problems, and temporary vision loss. NMOSD usually occurs in adulthood, but symptoms may start at any age. Some people have a single attack of symptoms lasting months, but in most people the symptoms come and go over time. People with NMOSD may develop permanent muscle weakness and vision loss.

The Sumaira Foundation is an international patient-led advocacy organization focused on rare neuroinflammatory and related disorders. Starting in NMOSD, the foundation now also works in MOGAD, autoimmune encephalitis, stiff person syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), neurosarcoidosis, and CNS vasculitis. The organization aims to raise awareness, educate patients, lead clinical research, build community, and advocate for patients.

Ms. Ahmed describes the excitement around the BEST-NMOSD multicenter, phase 4 trial that is enrolling 540 patients internationally, comparing rituxamab to complement inhibitors, inebilizumab and satralizumab (CIS) in patients with AQP4-IgG-positive NMOSD.

Adults with seropositive NMOSD meeting 2015 IPND criteria are randomised to rituximab or pooled CIS, then to complement inhibitors (ravulizumab, eculizumab), inebilizumab, or satralizumab. The primary endpoint is time to adjudicated relapse and time to protocol-defined safety or tolerability failure. Secondary outcomes include Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), treatment satisfaction, vision-related quality of life, pain, depression and fatigue.

The first patient was enrolled March 1st, 2025. No clinical outcome data are yet available. More data is expected to be presented at other conferences this year.

To learn more about NMOSD and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
NMOSD Overview 00:15
Personal Treatment Experience 00:44
The Sumaira Foundation 1:23
Upcoming Clinical Trial 3:06

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James Howard Jr., MD, Professor of Neurology at the University of North Carolina at Chapel Hill, discusses results from the ADAPT SERON clinical trial of efgartigimod IV in patients with seronegative generalized myasthenia gravis (gMG). Data from this trial was pivotal in efgartigimod's recent FDA approval.

MG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

At the American Academy of Neurology (AAN) 2026 meeting, data was presented on the phase 3 ADAPT SERON clinical trial evaluating the safety and efficacy of efgartigimod IV in adults with anti-MuSK-Ab positive, anti-LRP4-Ab positive, and/or triple seronegative gMG. Efgartigimod alfa is a first-in-class human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG autoantibodies.

In the double-blinded, placebo-controlled part A, adult patients were randomized to receive 4 once-weekly infusions of 10 mg/kg efgartigimod IV or placebo followed by a 5-week follow-up period. Part B included an open-label extension.

Topline results included 119 participants, 58 of whom received efgartigimod IV and 61 received placebo. The change in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score from baseline to week 4 was significantly different between efgartigimod IV (−3.35) and placebo (−1.90) groups. Incremental improvements in MG-ADL total scores were observed during part B over subsequent treatment cycles across all three subgroups. Efgartigimod IV was well tolerated, with no new safety signals observed.

To learn more about MG and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
Seronegative MG Overview 00:26
Diagnostic Challenges 00:54
ADAPT SERON Clinical Trial 2:08
Treatment Delay in Response 4:01
The Future of Treatment 4:43
Comparison to Rituximab 8:20

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