Jonathan Strober, MD, pediatric neurologist and neuromuscular specialist at the University of California at San Francisco, discusses the use of nipocalimab in adolescent patients with generalized myasthenia gravis (gMG).

gMG 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, which is due to the presence of antibodies against acetylcholine. The exact reason this occurs is not known.

Nipocalimab is a fully human IgG monoclonal antibody that binds to the neonatal Fc receptor (FcRn) with high specificity and affinity, blocking its interaction with IgG. The treatment is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of both adult and adolescent patients 12 years and older with gMG.

The objective of the study is to evaluate the safety and efficacy of nipocalimab in adolescents aged 12 to 18 years with gMG who exhibit an insufficient clinical response to standard-of-care therapy. Vibrance-mg (NCT05265273) is a phase 2/3 global, multicenter, open-label study evaluating nipocalimab plus standard of care in adolescents and children with gMG.

In adolescents with gMG, nipocalimab demonstrated a rapid, substantial and sustained reduction in total serum IgG levels over 24 weeks, with effects maintained through week 72 in the long term extension. Clinically meaningful improvements in MG Activities of Daily Living and Quantitative MG scores were achieved over 24 weeks and sustained in most participants through week 72. Treatment was well-tolerated in adolescents with gMG, with a favorable safety profile observed throughout the study.

Chapters:
Introduction 00:00
Myasthenia Gravis Overview 00:25
Data Presented at MGFA 2025 1:57
Next Steps 3:19

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Michael A. Levine, MD, ML, Children’s Hospital of Philadelphia, discusses positive topline results from the CALIBRATE trial of encaleret in patients with autosomal dominant hypocalcemia type 1 (ADH1).

ADH1 is a rare form of hypoparathyroidism caused by variants of the calcium‐sensing receptor gene (CASR). Inherited variants of CASR alter the set point for extracellular calcium, resulting in inadequate parathyroid hormone (PTH) secretion and inappropriate renal calcium excretion leading to hypocalcemia and hypercalciuria. The most common symptoms of ADH1 include muscle spasms in the hands and feet, muscle cramping, prickling or tingling sensations, and twitching of the nerves and muscles in various parts of the body.

Positive topline results from the CALIBRATE clinical trial were recently announced. CALIBRATE is a global phase 3 study evaluating the safety and efficacy of encaleret in patients with ADH1. The trial enrolled 70 adults with ADH1 and randomized 67 participants to encaleret and standard of care. Encaleret is an investigational, orally administered small molecule designed to selectively negatively modulate the calcium sensing receptor, targeting the underlying cause of ADH1.

The study met its primary endpoint, defined as the proportion of participants randomized to receive encaleret achieving both serum calcium and urine calcium levels in the respective target ranges. This was achieved by 76% of encaleret-treated participants compared to 4% for these same participants while on conventional therapy. The pre-specified key secondary analyses comparing encaleret to standard of care included a between group comparison on the proportion of participants achieving both target albumin-corrected serum and urine calcium, and comparisons of intact PTH above the lower limit of the reference range.

Additionally, by day 3 after randomization, 71% of participants assigned to encaleret had an albumin-corrected serum calcium within the reference range. At the end of the titration period at week 20, 98% of participants receiving encaleret had an albumin-corrected serum calcium in the target range, compared with 33% of participants on conventional therapy. Among encaleret responders at week 24, none required conventional therapy during Period 3. Encaleret achieved a mean increase in change from baseline of corrected calcium by 0.82 mg/dL from week 4 to week 24.

Encaleret achieved a mean reduction in change from baseline of 200 mg/day in 24-hour urine calcium from week 4 to week 24. Encaleret was well-tolerated with safety findings generally consistent with known ADH1 biology or related to the mechanism of action of encaleret.

There are plans to submit a New Drug Application (NDA) for encaleret to the U.S. Food and Drug Administration (FDA) in the first half of 2026. Future plans also include the initiation of a registrational trial of encaleret in pediatric patients with ADH1 in quarter 1 of 2026 and a phase 3 study of encaleret in adults with chronic hypoparathyroidism in 2026.

Chapters:
Introduction 00:00
ADH1 Overview 1:14
Current Management 4:21
Encaleret Overview 7:32
CALIBRATE Clinical Trial 9:42
Next Steps 14:03

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Nolan Campbell, PhD, U.S. Medical Director at Johnson & Johnson, discusses the EPIC clinical trial design that will evaluate the efficacy of nipocalimab versus efgartigimod in patients with generalized myasthenia gravis (gMG).

gMG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles due to antibodies attacking the acetylcholine receptors in the neuromuscular junction. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. Weakness tends to increase during periods of activity and improve after periods of rest. The condition results from a defect in the transmission of nerve impulses to muscles, which is due to the presence of antibodies against acetylcholine. The exact reason this occurs is not known. Some cases have been linked to tumors in the thymus gland. Some cases may go into remission temporarily, and muscle weakness may disappear so that medications can be discontinued.

Nipocalimab is a fully human neonatal FcRn inhibitor that enables the reduction of circulating IgG levels. It was approved earlier this year for the treatment of gMG following positive data from the Vibrance-MG clinical trial.

New data addressing unmet medical needs within the indication of nipocalimab was recently presented at the 2025 American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) meeting and the Myasthenia Gravis Foundation of America (MGFA) Scientific Session.

EPIC Clinical Trial Design

Efgartigimod is another FDA-approved FcRn-targeting treatment for gMG with differing molecular structures, binding affinities, and dosing to nipocalimab. EPIC (NCT07217587) is a phase 3b, multicenter, randomized, open-label, active-controlled interventional study with parallel-group design including treatment switching in adult participants with gMG.

The objective of EPIC aims to evaluate the efficacy of nipocalimab versus efgartigimod in participants initiating FcRn targeted therapy for gMG and to evaluate efficacy and safety of nipocalimab in participants switching from efgartigimod to nipocalimab. The study will consist of a screening phase of up to 32 days, a 12-week randomized open-label head-to-head phase (Arms 1 and 2) or an up to 12-week run-in phase and a 12-week open-label treatment switch phase (Arm 3), and an 8-week safety follow-up phase.

The study’s key primary and secondary endpoints are change from baseline in total immunoglobulin G (IgG) levels and sustained disease control measured by MG Activities of Daily Living and Quantitative MG scores 8-12 weeks post-initiation of treatment, respectively.

Insights and Challenges From Mapping Out the Patient Journey of gMG

Another study discussed at AANEM 2025 looked at the patient journey and further characterized the experience of living with gMG using key patient and caregiver insights from a pre-session survey and focus group discussions. There was a total of 16 participants, with 12 being patients and 4 caregivers.

Common challenges participants faced in the gMG patient journey included misdiagnosis or delayed diagnosis, insurance barriers, and the trial-and-error nature of finding effective treatments. Most participants described gMG as an emotionally challenging disease, due in part to self-doubt caused by HCPs not believing them, grief for lost abilities, and the emotional toll on caregivers of patients with gMG. Implementing self-care practices, finding support groups, and learning to identify limitations and triggers and express them to others were strategies participants utilized to improve their patient journey and protect their mental health. Leveraging these insights may help to improve gMG management and patient outcomes, as US patients with gMG continue to experience substantial disease instability despite currently available treatment options.

Chapters:
Introduction 00:00
Nipocalimab Overview 1:01
MGFA Poster Presentations 2:00
EPIC Clinical Trial 5:01
MG Patient Journey 7:00
Take Home Message 9:32

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Sindhu Ramchandren, MD, Executive Medical Director of Neuroscience at Johnson & Johnson, discusses long-term efficacy of nipocalimab in patients with generalized myasthenia gravis (gMG).

gMG 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, which is due to the presence of antibodies against acetylcholine. The exact reason this occurs is not known.

Nipocalimab is a neonatal Fc receptor-binding monoclonal antibody that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of gMG in adult and pediatric patients 12 years of age and older who are anti-AChR or anti-MuSK antibody positive.

Analysis of Long-Term Efficacy of Nipocalimab in Myasthenia Gravis: Open-Label Extension of the Vivacity-MG3 Trial

The Vivacity-MG3 (NCT04951622) clinical trial was a phase 3 double-blind, 24-week study that demonstrated statistically significant and clinically meaningful improvements in MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores with nipocalimab plus standard of care. Patients on nipocalimab plus standard of care in the double-blind phase had the option of continuing treatment in the open-label extension phase assessing long-term efficacy.

A total of 98 patients rolled over into the extension phase where data was collected up to week 48. At Week 48, 84.6% of patients achieved minimal clinical improvement (MCI) in MG-ADL. Mean time to earliest MCI was 4.0 weeks and sustained MCI for 8 weeks or greater was observed in 77.6% of patients. The mean percentage of time with MCI up to Week 48 was 71.6% and 50% or greater study time with MCI was observed in 73.9% of patients. 75% or greater study time with MCI was observed in 67.0% of patients.

At Week 48, 26.9% of patients achieved minimal symptom expression (MSE) in MG-ADL. Mean time to earliest MSE was 14.5 weeks and sustained MSE for 8 weeks or greater was observed in 23.5% of patients. Mean percentage of time with MSE up to Week 48 was 30.21% and 50% or greater study time with MSE was observed in 17.0% of patients while 75% or greater study time with MSE was observed in 12.5% of patients.

Efficacy of Nipocalimab in Adult Patients with Moderate-to-Severe Ocular Manifestations of gMG in Phase 3 VIVACITY-MG3

In gMG, 15–50% of patients present with ocular manifestations such as ptosis or diplopia. The objective of this post-hoc analysis was to evaluate the efficacy of nipocalimab versus placebo in the subgroup of patients with moderate-to-severe ocular manifestations (MSOM).

At baseline, within the MSOM subgroup, nipocalimab and placebo arms were comparable in mean age, BMI and mean (SD) MG-ADL-ocular and MG-ADL-total scores. At week 24, the change from baseline LS mean difference in MG-ADL scores was significantly greater with nipocalimab than placebo. The mean difference MG-ADL-total for nipocalimab vs placebo was −1.35. Additionally, at week 24, the change from baseline LS mean difference in MG-ADL-ocular scores was greater with nipocalimab than placebo. 51% of participants achieved meaningful within-person improvement at week 24 on MG-ADL-ocular domain with nipocalimab, comnpared to 24% in the placebo group.

Chapters:
Introduction 00:00
Myasthenia Gravis Overview 00:57
AANEM Poster Presentations 2:03
Take Home Message 7:35

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This accredited continuing education program is supported by an educational grant from Sanofi. Credit for the program can be obtained by visiting https://checkrare.com/learning/p-consider-rare-suspecting-and-diagnosing-cidp/ . 

This program, led by Jeffrey Allen, MD, Professor of Neurology at the University of Minnesota provides an overview on the diagnostic delays that often occur in patients with CIDP as well as best practices to suspect and diagnose this rare condition more efficiently. 

This activity has been designed to meet the educational needs of physicians specializing in family medicine, pediatrics, and neurology. 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 CIDP.
List best practices which can be used to diagnose CIDP more efficiently.

Faculty 
Jeffrey Allen, MD
Professor of Neurology
Department of Neurology
Division of Neuromuscular Medicine
University of Minnesota
Minneapolis, MN

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. Scott discloses 
Consultant/Educational talks: Annexon, Alexion, Amgen, CSL Behring, Takeda,
BioCryst, Grifols, Argenx, Sanofi, Immunovant, ImmunoAbs, Octapharma, Alnylam, AstraZeneca, Dianthus, Johnson & Johnson, Laboratoire Français du Fractionnement et des Biotechnologies, Nuvig, Akcea Therapeutics, ImmunoPharma,
Pfizer.

Community Faculty/Patient (Christine Eleeson): No relevant financial relationships with any ineligible companies.

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 0.5 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 any questions, please contact: [email protected]

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© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

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Philip Molyneaux, MD, PhD, a Professor of Interstitial Lung Disease (ILD) at Imperial College London and the Asthma+Lung UK Chair of Respiratory Research at Royal Brompton Hospital, where is also the Director of the UK National Institute for Health and Care Research (NIHR) Clinical Research Facility, discusses the results of the CORAL study.

Dr. Molyneaux, chief investigator of the CORAL phase 2b study, presented the results at CHEST 2025, held October 18-21, 2025 in Phoenix. He reported that up to 80% of patients with ILD have frequent, chronic cough. In CORAL, a randomized, double-blind, parallel-group study of 165 patients with idiopathic pulmonary fibrosis (the most common form of ILD) and a history of chronic cough, nalbuphine extended-release tablets were tested against placebo in reducing 24-hour cough frequency. All patients had a cough severity score of ≥ 4 on the Cough Severity Numerical Rating Scale at baseline.

Patients were randomly assigned to receive placebo or nalbuphine in one of three doses: 27-mg, 54-mg, or 108-mg tablets bid. The primary endpoint of the study was reduction in cough frequency at 6 weeks, measured via a digital cough monitor. Secondary endpoints included safety, and changes in several patient-reported questionnaires and scoring indexes.

All doses produced statistically significant decreases in 24-hour cough frequency, but the higher doses produced greater reductions from baseline at 6 weeks compared with placebo (placebo, –17%; nalbuphine 27 mg, –48%, nalbuphine 54 mg, –53%; nalbuphine 108 mg, –60%). Furthermore, a reduction in cough was seen by week 2.

For patients receiving active therapy, the most common adverse events were nausea, vomiting, constipation, and dizziness. There was no difference in discontinuation rates in patients receiving placebo or any nalbuphine doses.

Dr. Molyneaux stated that not only did objectively measured cough frequency decrease, but patients also gained additional benefits within 2 weeks of taking nalbuphine, as determined by patient-reported outcomes data.

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Aman Chauhan, MD, Oncologist at the University of Miami, discusses details of a phase 3 study testing paltusotine in patients with carcinoid syndrome due to neuroendocrine tumors (NETs).

NETs are rare tumors that usually develop in the GI tract or lungs, but may develop in other parts of the body, such as the pancreas, testicle, or ovary. In later stages, symptoms may vary depending on where the tumor is located. 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. The cause of neuroendocrine neoplasms is unknown.

Paltusotine is a selectively-targeted somatostatin receptor type 2(SST2) nonpeptide. The treatment is currently approved by the U.S. Food and Drug Administration (FDA) for patients with acromegaly.

The phase 3 CAREFNDR (NCT07087054) clinical trial is a randomized, international, multicenter, placebo-controlled, double-blind study evaluating paltusotine in carcinoid syndrome due to NET. Patients will be treated for 16 weeks with a primary endpoint of change from baseline in flushing frequency at week 12. A second phase 3 trial is also in development, testing the nonpeptide drug candidate, CRN09682, in patients with somatostatin receptor 2-expressing tumors. The CAREFNDR study is currently enrolling patients. For more information, visit carefndr.com.

This study builds on a phase 2 study previously presented. Results from this study in carcinoid syndrome demonstrated rapid and sustained reductions in flushing episodes and bowel movement frequency. A preliminary analysis of phase 2 data from the open-label trial of paltusotine in the treatment of patients with carcinoid syndrome due to NETs showed an overall investigator-assessed progression free survival rate of 74% following one year of treatment.

Chapters:
Introduction 00:00
Carcinoid Syndrome 00:58
Current Management 2:49
Ongoing Phase 3 Clinical Trials 4:52
Next Steps 7:57

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Alexandra C. Bayer Wildberger, PhD, Post-Doctoral Associate at Yale School of Medicine, discusses the shift to precision medicine in myasthenia gravis (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, which in the majority of patients is due to the presence of antibodies against acetylcholine receptor (AChR). The exact reason this occurs is not known.

As Dr. Bayer explains, the therapeutic landscape for MG has greatly evolved past traditional immunosuppressants over the last few years. The advent of mechanism-based therapies, such as FcRn inhibitors, complement inhibitors, and the potential for isotype-specific proteases, are providing patients with more tailored treatment options.

Due to the heterogeneity of MG, the biggest challenge at present is identifying the most effective treatment for a patient’s specific underlying mechanism of disease. Dr. Bayer explains how this will help to optimize the usage of resources in disease treatment and reduce unnecessary side effects and exposure to treatments that are not beneficial to individual patients.

Current research is striving to better understand the complexities behind MG, such as the exact presence of immunoglobulin classes and the roles they play in the disease, to move towards a precision medicine approach. Recently, Yale has published work describing a previously unrecognized subset of patients with IgM-AChR specific autoantibodies. Next steps involve understanding the role of these autoantibodies in vivo.

Dr. Bayer notes the key role that the RDCRN’s MGNet has played in their research. Through scientific and clinical resources, such as clinical samples and data from the network’s biorepository and funding for further research, the consortium is helping to accelerate the understanding and more effective treatment of MG.

Chapters:
Introduction 00:00
AChR-Positive Myasthenia Gravis 00:26
Need for Tailored Therapeutics 1:37
Ongoing Research 3:23
RDCRN MG Consortium 4:38

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Naomi Patel, MD, MPH, Rheumatologist at Massachusetts General Hospital, discusses long-term data from the AQUARIUS study of avacopan in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

GPA is a type of vasculitis causing swelling of the blood vessels anywhere in the body. The condition mainly impacts the sinuses, nose, trachea, lungs, and kidneys. The swelling can limit the flow of blood to these body parts, causing damage. Symptoms of the disease can include sinus pain, recurrent respiratory infections, joint pain, fatigue, and skin lesions. The exact cause of GPA is unknown, but it is a type of autoimmune disease. MPA is also a type of vasculitis. The kidneys, lungs, nerves, skin, and joints are the most commonly affected areas of the body. The cause of this disorder is unknown.

Avacopan is a selective oral C5a receptor antagonist that was approved by the U.S. Food and Drug Administration (FDA) for the treatment of GPA/MPA in 2021. Data was recently presented at ACR and Kidney Week (ASN) from the AQUARIUS clinical trial of avacopan in patients with GPA/MPA.

Data From ACR Presentation (AQUARIUS Part 1) One-Year Real-World Effectiveness with Avacopan in GPA and MPA

This ongoing retrospective cohort study describes 12-month effectiveness and safety outcomes for avacopan in patients with GPA/MPA.

Among the 95 patients with available 12 month follow-up data, 64% were in remission at month 6, while at month 12, 95% had a BVAS v3 equal to zero, 87% were glucocorticoid-free, and 61% had sustained remission. The median discontinuation time was three months and the majority of patients experienced no worsening of glucocorticoid toxicity.

Sustained remission was similar in those with baseline kidney, lung, or ENT involvement. The most common GTI-MD domain with net worsening was blood pressure, followed by body mass index, lipid metabolism, and glucose tolerance. The majority had no net worsening of metabolic GC toxicity over 12 months, indicating either net improvement or no change.

Data From ASN Presentation of AQUARIUS Real-World Clinical Outcomes in a Large Health Care System After Avacopan Initiation for Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA) Involving the Kidneys

This is a retrospective cohort study of patients prescribed avacopan for GPA/MPA from December 1, 2021 to April 1, 2024, reporting 12-month outcomes in those with baseline kidney involvement.

Among 58 patients with kidney involvement treated with avacopan, 16% received dialysis less than or equal to 1 month following initiation. Of 54 patients with 12 month follow-up, 69% had sustained remission. Median estimated glomerular filtration rate (eGFR) among those not on dialysis at baseline and 12 months was 35 and 44, respectively. 4% of patients newly initiated dialysis greater than 1 month after avacopan initiation. Of 7 patients on dialysis at baseline with complete follow-up, 86% discontinued dialysis by 12 months. Among those with baseline urine protein:creatinine ratio (UPCR) greater than 2 g/g, median UPCR declined from 1.4 at baseline to 0.3 g/g at 12 months.

Chapters:
Introduction 00:00
GPA/MPA Overview 00:16
AQUARIUS Clinical Trial 1:01
Prior Treatment 2:54
Results of Trial 4:24
Take Home Message 9:00

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