Gavin Lindberg discusses the EVAN Foundation and their initiatives to help patients and families with neuroblastoma.

Neuroblastoma is a rare neuroendocrine tumor that develops from neuroblasts, or immature nerve tissue. It most often develops in infancy and may be diagnosed in the first month of life. Most cases present before the age of 5.

The tumor most often develops in the adrenal gland, but may develop in the neck, chest, or spinal cord. It is considered an aggressive tumor because it often spreads to other parts of the body, frequently before it is diagnosed. Neuroblastoma can cause a variety of signs and symptoms, including a lump where the tumor is growing, bone pain, diarrhea, and various neurological symptoms.

The cause of most neuroblastomas is not known. Rarely, a neuroblastoma is caused by an inherited genetic change in a gene, such as the ALK gene or PHOX2B gene. However, many biological markers of neuroblastoma have been discovered, of which the most important is MYCN. This oncogene is overexpressed in nearly 25% of patients with neuroblastoma

Diagnosing neuroblastoma may rely on a physical examination, blood tests, imaging tests (such as MRI or CT scan) and ultimately, a biopsy. Studies are typically done on CBC, renal function, liver function, electrolytes, and LDH.

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Gavin Lindberg provides advice to families of patients with neuroblastoma.

Neuroblastoma is a rare neuroendocrine tumor that develops from neuroblasts, or immature nerve tissue. It most often develops in infancy and may be diagnosed in the first month of life. Most cases present before the age of 5.

The tumor most often develops in the adrenal gland, but may develop in the neck, chest, or spinal cord. It is considered an aggressive tumor because it often spreads to other parts of the body, frequently before it is diagnosed. Neuroblastoma can cause a variety of signs and symptoms, including a lump where the tumor is growing, bone pain, diarrhea, and various neurological symptoms.

The cause of most neuroblastomas is not known. Rarely, a neuroblastoma is caused by an inherited genetic change in a gene, such as the ALK gene or PHOX2B gene. However, many biological markers of neuroblastoma have been discovered, of which the most important is MYCN. This oncogene is overexpressed in nearly 25% of patients with neuroblastoma

Diagnosing neuroblastoma may rely on a physical examination, blood tests, imaging tests (such as MRI or CT scan) and ultimately, a biopsy. Studies are typically done on CBC, renal function, liver function, electrolytes, and LDH.

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Gavin Lindberg details his family’s experience with neuroblastoma and navigating a rare disease diagnosis.

Neuroblastoma is a rare neuroendocrine tumor that develops from neuroblasts, or immature nerve tissue. It most often develops in infancy and may be diagnosed in the first month of life. Most cases present before the age of 5.

The tumor most often develops in the adrenal gland, but may develop in the neck, chest, or spinal cord. It is considered an aggressive tumor because it often spreads to other parts of the body, frequently before it is diagnosed. Neuroblastoma can cause a variety of signs and symptoms, including a lump where the tumor is growing, bone pain, diarrhea, and various neurological symptoms.

The cause of most neuroblastomas is not known. Rarely, a neuroblastoma is caused by an inherited genetic change in a gene, such as the ALK gene or PHOX2B gene. However, many biological markers of neuroblastoma have been discovered, of which the most important is MYCN. This oncogene is overexpressed in nearly 25% of patients with neuroblastoma

Diagnosing neuroblastoma may rely on a physical examination, blood tests, imaging tests (such as MRI or CT scan) and ultimately, a biopsy. Studies are typically done on CBC, renal function, liver function, electrolytes, and LDH.

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Gavin Lindberg details his family’s experience with neuroblastoma, provides advice to families, and discusses the EVAN Foundation.

Neuroblastoma is a rare neuroendocrine tumor that develops from neuroblasts, or immature nerve tissue. It most often develops in infancy and may be diagnosed in the first month of life. Most cases present before the age of 5.

The tumor most often develops in the adrenal gland, but may develop in the neck, chest, or spinal cord. It is considered an aggressive tumor because it often spreads to other parts of the body, frequently before it is diagnosed. Neuroblastoma can cause a variety of signs and symptoms, including a lump where the tumor is growing, bone pain, diarrhea, and various neurological symptoms.

The cause of most neuroblastomas is not known. Rarely, a neuroblastoma is caused by an inherited genetic change in a gene, such as the ALK gene or PHOX2B gene. However, many biological markers of neuroblastoma have been discovered, of which the most important is MYCN. This oncogene is overexpressed in nearly 25% of patients with neuroblastoma

Diagnosing neuroblastoma may rely on a physical examination, blood tests, imaging tests (such as MRI or CT scan) and ultimately, a biopsy. Studies are typically done on CBC, renal function, liver function, electrolytes, and LDH.

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Shellye Horowitz, a patient with hemophilia and advocate, discusses the impact of hemophilia on women and girls.

Hemophilia is a bleeding disorder that slows the blood clotting process. People with this disorder experience prolonged bleeding following an injury or surgery. In severe cases, heavy bleeding occurs after minor trauma or in the absence of injury.

Historically, hemophilia was thought to be a “male” disease. This belief has caused prolonged effects on women and girls with the disorder. Significant delays in diagnosis and misdiagnosis are common and cause great impact on physical and mental health. Undiagnosed hemophilia can lead to heavy menstrual bleeding, prolonged bleeding following surgery, anemia, easy bruising, joint damage, and severe discomfort.

A recent article published in The Journal of Haemophilia predicted that there are over 1 million women with hemophilia in the world. However, it is likely that the majority of these patients are not receiving proper care. Shellye’s diagnostic journey is proof of this unmet need in the hemophilia community. Although she exhibited signs of hemophilia from an early age and had a family history of the disease, a proper diagnosis was not given until her 40s. Because of this, she is now an advocate for hemophilia awareness and improvement to care, especially for girls and women.

To better understand the impact of hemophilia on women and girls, the Hemophilia Life Stages and Changes Global Survey was conducted. This survey assessed how hemophilia affects women's lives in areas including challenges with family planning, physical activity, and mental health. Key findings included that 59% of women were over the age of 25 when they first received their diagnosis. Further, 65% of women stated they experienced a negative impact on their ability to start a family and over 70% said travel and level of physical activity were negatively impacted. The impact of mental health was also significant, with 30% being diagnosed with anxiety and 23% with depression.

In addition to this survey, the Hemophilia Through My Eyes Video Series sheds light on patient stories, including Shellye’s, by giving a personal look at the realities of living with this disease.

Chapters:
Introduction 00:00
Misconceptions of Hemophilia 00:57
Diagnostic Journey 2:44
Importance of Early Diagnosis 4:47
Newborn Screening 7:13
Message to Physicians 8:49
Hemophilia Life Stages and Changes Global Survey 10:15
Through My Eyes Video Series 14:12

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Sindhu Ramchandren, MD, Executive Medical Director, Neuroscience and Disease Cluster Lead for Neuroimmunology and Neuromuscular Disorders at Johnson & Johnson, discusses updated results from the Vivacity-MG3 clinical trial in patients with generalized 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. 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 receptors. The etiology of MG is not known.

The Vivacity-MG3 clinical trial (NCT04951622) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of nipocalimab in patients with antibody-positive generalized MG. There is also an ongoing open-label extension evaluating the long-term safety and efficacy of nipocalimab in patients with MG. Nipocalimab is an investigational monoclonal antibody designed to block FcRn and reduce levels of circulation immunoglobulin G (IgG) antibodies.

Results of the study showed that patients treated with nipocalimab plus standard of care maintained improvements in their MG-ADL and QMG scores over 84 weeks with sustained reductions in total IgG. The mean change in MG-ADL score was -5.64 from baseline after 60 weeks in the open-label extension participants receiving nipocalimab plus standard of care. The mean change in MG-ADL score for participants who transitioned from placebo and standard of care to nipocalimab plus standard of care was -6.01. 45% of patients in the antibody-positive population receiving steroids at baseline were able to decrease or discontinue use. The safety profile of nipocalimab was consistent and tolerable throughout the open-label extension.

Additionally, patients treated with nipocalimab plus standard of care achieved statistically significant improvements in QMG scores by -4.9 compared to placebo plus standard of care. Patients in the nipocalimab plus standard of care group were also four times more likely to sustain symptom improvement at 20 weeks compared to the placebo plus standard of care group. 36.4% of patients treated with nipocalimab versus 10.5% of patients on placebo spent greater than 75% of the study duration demonstrating improvements in QMG score.

Chapters:
Introduction 00:00
Myasthenia Gravis Overview 0:33
Nipocalimab Overview 2:21
Vivacity-MG3 Study 3:19
Take Home Message 7:45

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Michael Weiss, MD, Department of Neurology, University of Washington Medical Center, discusses results from the RAISE clinical trial in patients with 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. 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.

The RAISE clinical trial (NCT04115293) is a phase 3, multicenter, double-blind, placebo-controlled study evaluating zilucoplan in adult patients with MG. The primary objectives of the study were to evaluate the effect of zilucoplan on the Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores in patients with generalized MG. Zilucoplan is a macrocyclic peptide complement component 5 inhibitor and was administered as a daily subcutaneous injection at a dose of 0.3 mg/kg for 12 weeks.

At week 12, least-squares mean (LSM) change from baseline in MG-ADL total score was -4.39 for the zilucoplan treated group comopare to -2.30 for placebo. LSM change from baeline for QMG total score was -6.19 for zilucoplan and -3.25 for placebo. Mean change from baseline in AG-ADL subdomain scores in the zilucoplan versus placebo groups were: ocular, –1.5 vs –0.8 ; bulbar, –1.9 vs –1.1; respiratory, –0.4 vs –0.3; limb/axial, −1.2 vs –0.8. Mean CFB in QMG subdomain scores were: ocular, −2.0 vs −1.3; bulbar, −1.6 vs −1.1; respiratory, −0.6 vs −0.3; limb/axial, −2.9 vs −1.2.

These results further support zilucoplan’s ability to provide rapid and clinically meaningful improvements in MG-ADL and QMG scores compared to placebo.

Chapters:
Introduction 00:00
RAISE Clinical Trial 2:24
Choosing Treatment Options 4:02
AAN 2025 Talk 5:19

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Richard Lafayette, MD, Professor of Medicine, Nephrology and Director of the Glomerular Disease Center at Stanford University Medical Center, discusses the recent approval of Vanrafia (atrasentan) for patients with IgA nephropathy (IgAN).

IgAN is a rare disorder that occurs when IgA accumulates in the kidneys. In the early stages, IgAN has no symptoms. The first sign of this condition may be blood in the urine. If left untreated, end-stage kidney disease may develop. In most instances, the cause of this condition is unknown; however, certain disorders have been linked with IgAN, such as cirrhosis of the liver, celiac disease, and HIV infection.

Atrasentan is a potent, selective endothelin A (ETA) receptor antagonist that targets the reduction of proteinuria in adults with IgAN that are at risk of rapid disease progression. It is administered as a once-daily oral treatment that can be added on to supportive care.

The accelerated approval follows an interim analysis of the phase 3 ALIGN study (NCT04573478), a global, randomized, multicenter, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of atrasentan. The primary efficacy endpoint was change in proteinuria as measured by 24-hour urine protein-to-creatinine ratio (UPCR) from baseline to week 36. Secondary endpoints included change in kidney function from baseline to week 36 as well as safety and tolerability.

Based on data from the interim analysis, atrasentan has achieved statistically significant reductions of 36% in proteinuria at week 36 compared to placebo. These results were observed as early as week 6 and sustained through week 36. This effect was consistent across patient subgroups including age, sex, race, and baseline disease characteristics in the main study cohort. Additionally, similar effects were observed in a group of patients treated with both a RAS inhibitor and an SGLT2 inhibitor, with a 37.4% reduction in proteinuria at week 36 versus placebo.

Study results have also illustrated a favorable safety profile for atrasentan with adverse events reported in 2% or greater of patients. The most common adverse events include peripheral edema, anemia, and liver transaminase elevation.

Chapters:
Introduction 00:00
IgA Nephropathy Overview 00:24
Common Symptoms 1:35
Current Management 2:18
Atrasentan Overview 3:16
ALIGN Clinical Trial 4:24

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Paul Bolno, MD, President and Chief Executive Officer of Wave Life Sciences, discusses positive results from the FORWARD-53 clinical trial evaluating WVE-N531 in patients with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping.


DMD affects the muscles, leading to muscle wasting that gets worse over time. DMD occurs primarily in males, though in rare cases may affect females. The symptoms of DMD include progressive weakness and atrophy of both skeletal and heart muscles. Early signs may include delayed ability to sit, stand, or walk and difficulties learning to speak. DMD is caused by genetic changes in the Dystrophin gene.


The FORWARD-53 study is a phase 2 clinical trial evaluating WVE-N531 in patients with DMD who are amenable to exon 53 skipping. WVE-N631 is an exon skipping oligonucleotide. The analysis of the study was conducted after 48 weeks of treatment with a 10 mg/kg dose of WVE-N531 every two weeks.


Observations from this study revealed significant improvements in muscle health with exon skipping, with a 28.6% reduction in fibrosis and transition from regenerative to mature muscle. A statistically significant and clinically meaningful improvement of 3.8 seconds in Time-to-Rise vs natural history was also observed. Additional functional benefits were observed on the North Star Ambulatory Assessment (NSAA) versus natural history, and in hand grip strength versus baseline.

Dystrophin expression was stabilized between 24 and 48 weeks and averaged 7.8%, with 88% of participants above 5% average dystrophin. A 50% decline in creatine kinase, as well as decreases in IL-6 and MCP-1, were also observed. Additionally, the safety and tolerability profile of WVE-N531 was favorable with no serious adverse events

A New Drug Application for accelerated approval is expected to be filed in 2026.

Chapters:
Introduction 00:00
DMD Overview 1:14
FORWARD-53 Clinical Trial 3:48
Next Steps 11:06
What Physicians Should Know 11:36

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