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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Logan Schneider, MD, Adjunct Clinical Associate Professor of Psychiatry and Behavioral Sciences at Stanford University, discusses the DUET clinical trial of Xywav (low sodium oxybate) in patients with narcolepsy.

Narcolepsy is a chronic neurological disorder characterized by an inability of the brain to control sleep-wake cycles. Patients with narcolepsy typically enter REM sleep more quickly, causing the boundaries between wakefulness and sleep to blur. This causes fragmented sleep at night as well as muscle weakness and dream activity while awake. Common symptoms include excessive daytime sleepiness, cataplexy, sleep paralysis, and hallucinations.

At the American Academy of Neurology (AAN) 2026 Annual Meeting, data was presented on the impact of low-sodium oxybate dosages greater than 9 g/night on cognitive complaints, functional impairments, work productivity, and symptom severity in participants with narcolepsy who may benefit from higher LXB dosages.

The DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment), a prospective, open-label study (NCT05875974), evaluated the safety and efficacy of low-sodium oxybate in narcolepsy or idiopathic hypersomnia.

A total of 48 patients were enrolled and treated with low-sodium oxybate greater than 9g. Total low-sodium oxybate dosage at stable-dose period (n=45) was 11.1 ± 1.0 g/night. Patient Global Impression of Severity endorsement of ‘severe’ overall disease was 61.4% (9g) versus 29.5% (greater than 9g), with 92.3% of participants reporting overall disease improvement on Patient Global Impression of Change. Mean British Columbia Cognitive Complaints Inventory total scores decreased from 6.9 ± 0.6 on 9g to 5.1 ± 0.7 on greater than 9g, with fewer participants reporting moderate-to-severe cognitive complaints (34.1% to 18.2%).

Mean Functional Outcomes of Sleep Questionnaire-10 total scores in the 9g vs greater than 9g cohorts were 13.6 ± 0.6/14.8 ± 0.6. Work Productivity and Activity Impairment scores also showed trends of improvement in the greater than 9 cohort.

Treatment-emergent adverse events were consistent with the known low-sodium oxybate safety profile.

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

CHAPTERS
Introduction 00:00
Current Management 00:29
DUET Clinical Trial Data 1:31
Clinical Implications on Dose Optimization 4:42
Addressing Unmet Needs 6:47
Take Home Message 8:52

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Omar Sinno, MD, US Medical Strategy Lead for Rare Disease at UCB Pharma, discusses data presented on myasthenia gravis (MG) at the 2026 American Academy of Neurology meeting.

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 2026 American Academy of Neurology meeting, UCB presented various datasets on MG:

Data on Zilbrysq (zilucoplan), a complement C5 inhibitor approved for the treatment of generalized MG in adult patients who are anti-AChR Ab positive. The treatment is available as a prefilled syringe and an auto-injector. Recent data shows the auto-injector has a 99.8% bioavailability similar to the prefilled syringe and patients treated showed minimal symptom expression.

Rystiggo (rozanolixizumab), a humanized monoclonal antibody designed to block FcRn in adults with anti-AChR Ab positive or anti-MuSK Ab positive MG, illustrated consistency of response after the first cycle. Additionally, in patients who did not respond well after the first cycle, a good response was observed after the second cycle of treatment.

Additional data presented focused on health equity and treatment guidance/goals. Mr. Sinno stresses the importance of giving patients options in terms of their treatment and care. Because all patients are different, establishing comprehensive treatment goals for each individual is a current focus for the company.

Another focus is addressing disparities between patient populations, including those between patients in rural versus suburban/urban areas and the longer time-to-diagnosis and more severe presentations seen in the African American population.

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

CHAPTERS
Introduction 00:00
MG Data at AAN 2026 00:14
Addressing Population Disparities 2:20
Focus on Patient Outcomes 3:15

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Mauro Cives, MD, Associate Professor of Medical Oncology at the University of Bari, Italy, discusses the upcoming regulatory decision for LNTH-2501 to improve imaging of neuroendocrine tumors (NETs).

NETs are rare tumors that usually develop in the gastrointestinal tract or lungs, but may develop in other parts of the body, such as the pancreas, testicle, or ovary. The tumor may produce hormone-like substances that spread to the body and cause symptoms of carcinoid syndrome, such as flushing of the face and chest, diarrhea, and trouble breathing. Symptoms may vary depending on where the tumor is located.NETs are also hard to diagnose due to their clinically challenging presentation.The cause of NETs is unknown.

Dr. Cives explains how imaging, both anatomical and functional, plays a key role in diagnosis and treatment. Particularly, anatomical (i.e., CT scan, MRI) scanning can give information regarding the location and burden of the tumor masses. Functional imaging (i.e., gallium PET/CT scan) can provide information on location and expression of somatostatin receptors on the surface of the tumor cells.

LNTH-2501 (Kit for Preparation of Ga 68 edotreotide Injection) is a radioactive diagnostic kit designed to support PET imaging for localization of somatostatin receptor positive NETs in adult and pediatric patients. LNTH-2501 has a US Food and Drug Administration (FDA) PDUFA date of June 29, 2026. The approval will give the ability to detect these malignancies and understand if they can be effectively treated by peptide receptor radionuclide therapy (PRRT).

Dr. Cives also highlights the importance of referring patients to Centers of Excellence to get the specific care they need and have access to all technology and treatments available for NETs.

To learn more about NETs and other rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/

CHAPTERS
Introduction 00:00
Diagnostic Challenges 00:22
Role of Imaging 1:45
LNTH-2501 Impact on Diagnosis and Management 3:05
Improving Care in NETs 4:08

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Pablo Villoslada, MD, PhD, Founder and Medical Director of Accure Therapeutics and Head of Pathogenesis and New Therapies MS at IDIBAPS in Hospital Clínic in Barcelona, discusses results from the ACUITY clinical trial testing privosegtor to treat patients with acute optic neuritis (AON). The data was recently presented at the American Academy of Neurology Annual Meeting (AAN 2026) in Chicago, IL.

AON is an inflammation of the optic nerve that can be caused by different systemic and neurological disorders. It is commonly presented as a subacute unilateral painful vision loss. It may also present in the setting of different systemic and neurological disorders such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin-oligodendrocyte glycoprotein antibody-associated disease. The exact underlying cause of AON is unknown but it is believed to have autoimmune involvement.

The ACUITY phase 2 multi-center, randomized, double-masked, placebo-controlled clinical trial evaluated the efficacy, safety, and tolerability of privosegtor in AON. Privosegtor is a peptoid small molecule that has demonstrated neuroprotective activity.

A total of 33 patients were included in the modified intention-to-treat analysis. Improvement in low contrast visual acuity (LCVA) compared to placebo with privosegtor 3 mg/kg/day was 18.2 letters at month 3, and 14.8 letters at month 6. There was a 43% reduction in ganglion cell/inner plexiform layer (GCIPL) thinning compared to placebo at months 3 and 6, and a 28% and 30% reduction in retinal nerve fiber layer (RNFL) thinning at month 3 and month 6, respectively.

Mean plasma neurofilament-light (NfL) concentrations remained stable from baseline to month 1 at 7.6 µg/ml and month 6 at 5.8 µg/ml with privosegtor. The placebo group showed a significant increase from baseline (8.6 µg/ml) at month 1 (14.6 µg/ml), followed by a steady decline to month 6 (9.3 µg/ml).

Privosegtor was generally well-tolerated and adverse events showed no differences in incidence between groups, with no drug-related serious adverse events.

For more information on AON and other rare ophthalmology conditions, visit https://checkrare.com/diseases/ophthalmology-eye-diseases/

CHAPTERS
Introduction 00:00
AON Overview 00:14
ACUITY Clinical Trial 1:05
Privosegtor Mechanism of Action 4:45
Next Steps: PIONEER Clinical Program 6:32

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This accredited continuing education program is supported by an educational grant from Blueprint Medicine. 

It provides timely and practical education on systemic mastocytosis (SM). To obtain CME credit, visit https://checkrare.com/learning/p-systemic-mastocytosis-recognition-diagnosis-and-clinical-management/

SM is a rare, chronic disorder driven by aberrant mast cell accumulation across multiple organ systems. Although diagnostic criteria are well established, a recent natural history study found that the average time to diagnosis is nearly five years. This prolonged delay—largely due to limited awareness of SM and its early symptoms—often results in unnecessary disease progression and inappropriate treatment. To address this clinical gap, this activity, led by Daniel J. DeAngelo, MD, PhD, Chief, Division of Leukemia at the Dana-Farber Cancer Institute, Harvard Medical School, in Boston, MA, provides an overview of the early signs and symptoms of SM, outlines the appropriate diagnostic criteria and tools, and reinforces the importance of timely referral and testing for these patients to be properly managed. 

Led by a clinical expert with experience diagnosing and treating patients with SM, this 45-minute CME program will highlight early signs of SM, outline diagnostic criteria and tools, and reinforce the importance of timely referral/testing. 

Target Audience
This activity has been designed to meet the educational needs of physicians specializing in hematology, dermatology, gastroenterology, immunology, and family practice. Other members of the care team may also participate.

Learning Objectives
After participating in the activity, learners should be better able to:
Describe the early symptoms of systemic mastocytosis and its clinical relevance.
Apply best practices to diagnose systemic mastocytosis more efficiently.

Faculty
Daniel J. DeAngelo, MD, PhD
Chief, Division of Leukemia
Dana-Farber Cancer Institute,
Harvard Medical School
Boston, MA

Disclosure Statement
According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.

Disclosure of relevant financial relationships are as follows:

Faculty Educator/Planner
Dr. DeAngelo discloses the following relevant financial relationships with ineligible companies:
Consultant: Amgen, Autolos, Blueprint Medicines, Incyte, Jazz, Novartis, Pfizer, and Takeda 
Research Support: AbbVie, Glycomimetics, Novartis, and Blueprint Medicines
Data Safety Monitoring Board: Daiichi-Sankyo

Other Planners for this activity have no relevant financial relationships with any ineligible companies.

This activity will review off-label or investigational information.

The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.
Accreditation and Credit Designation

In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physicians
American Academy of CME, Inc., designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. 

Other HCPs
Other members of the care team will receive a certificate of participation.
There are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days.

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For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare’s privacy policy, please access https://checkrare.com/privacy/

Contact
For any questions, please contact: [email protected]

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