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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Carla Nester, MD, Professor of Pediatrics-Nephrology at the University of Iowa, discusses the recent U.S. Food and Drug Administration (FDA) approval of iptacopan as the first and only treatment of adults with C3 glomerulopathy (C3G).

C3G is a rare kidney disease characterized by damage to kidney glomeruli due to abnormal activation of the complement system. When C3 proteins get lodged in the kidney, glomeruli get injured and buildup of toxins and reduced urine production occur. This can ultimately lead to declined kidney function. Common signs and symptoms include:

Hematuria
Proteinuria
Reduced glomerular filtration rate and increased creatinine levels
Fatigue
Edema of the hands, feet, and ankles

Iptacopan is an oral inhibitor of the alternative complement pathway that targets the underlying cause of C3G. It is the first approved treatment for C3G. This approval follows positive data from the APPEAR-C3G clinical trial.

The APPEAR-C3G clinical trial was a phase 3, multicenter, randomized, double-blind, parallel group, placebo-controlled study evaluating the safety and efficacy of twice-daily oral iptacopan in patients with C3G. The study included a 6-month randomized, double-blind treatment period with iptacopan compared to placebo and was followed by an additional 6-month, open-label treatment period where all participants received iptacopan. The primary endpoint of the first period was proteinuria reduction from baseline at 6 months compared to placebo, measured by 24-hour urine protein-creatinine ratio.

Results observed in the study included a clinically meaningful reduction in proteinuria with iptacopan. This reduction was seen as early as 14 days into treatment and was sustained at 12 months. In the open-label period, proteinuria reduction was also seen in participants who had switched from placebo to iptacopan.

Additionally, a favorable safety profile was observed. The most common adverse reactions included nasopharyngitis and viral infections.

Chapters:
Introduction 00:00
C3G Overview 00:37
Fabhalta Overview 2:12
APPEAR-C3G Clinical Trial 4:19
Take Home Message 6:55
Treatment Safety 8:08

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Richard J. Nowak, MD, Director of the Myasthenia Gravis Clinic at Yale University, discusses positive data from the MINT clinical trial evaluating Uplizna (inebilizumab-cdon) in adults with generalized myasthenia gravis (gMG).

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

The MINT study (NCT04524273) is a phase 3, randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluating the safety and efficacy of inebilizumab in adults with gMG. Inebilizumab is an anti-CD-19 antibody that causes targeted and sustained depletion of CD19+ B cells that contribute to underlying disease progression.

The trial enrolled 238 patients with gMG, with 190 patients who are acetylcholine receptor autoantibody-positive (AChR+), and 48 who are muscle-specific kinase autoantibody-positive (MuSK+). The primary endpoint of this study is change from baseline in MG Activities of Daily Life (MG-ADL) score at week 26 in the combined population.

Results demonstrated a durable efficacy over the 52-week period in patients with AChR+ gMG with two doses per year after initial loading dose. Among the AChR+ population treated with inebilizumab, 72.3% had a 3 point or greater improvement in MG-ADL score, compared to 45.2% in the placebo group. Change from baseline in Quantitative MG score was also greater for patients treated with inebilizumab compared to placebo, with 69.2% of AChR+ patients improving by 3 or more points, compared to 41.8% in the placebo group.

Sustained efficacy was also observed with protocol-specified steroid taper. Starting at week4, all patients reduced prednisone use to 5 mg per day by week 24. Additionally, no new safety signals were identified. The most common adverse events were infusion-related reactions, nasopharyngitis, and urinary tract infections.

Chapters:
Introduction 00:00
Inebilizumab Overview 00:20
MINT Clinical Trial 1:53
Importance of Treatment Options 4:26

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Ashley Shoemaker, MD, Associate Professor of Pediatrics and Pediatric Endocrinology at Vanderbilt University, discusses the approval of Vykat XR (diazoxide choline) for the treatment of hyperphagia in patients ages 4 years and older with Prader-Willi syndrome (PWS).

PWS is a rare genetic condition that affects many parts of the body but its most dominant symptom is overwhelming hyperphagia. Infants with PWS also have severe hypotonia, feeding difficulties, slow growth, short stature, hypogonadism, developmental delays, cognitive impairment, and distinctive behavioral characteristics such as temper tantrums, stubbornness, and obsessive-compulsive tendencies. PWS is caused by gene mutations on chromosome 15.

Diazoxide choline is a once-daily oral treatment that is capable of activating the adenosine triphosphate-sensitive potassium channel and crossing the blood-brain barrier. It is the first therapy to be approved for the treatment of hyperphagia in PWS.

The approval follows positive data from the phase 3, multienter, randomized withdrawal, double-blind, placebo-controlled clinical trial. Results demonstrated a statistically significant increase in hyperphagia for those randomized to switch to placebo compared to those who remained on diazoxide choline. Prior to this randomized withdrawal period, participants received double-blind and/or open-label diazoxide choline for a mean duration of 3.3 years.

Additionally, the safety profile of the therapy is favorable with the most common adverse events being hypertrichosis, edema, hyperglycemia, and rash. These occurred in greater than or equal to 10% of participants.

The treatment is expected to be available to patients in the U.S. in early April 2025.

Chapters:
Introduction 00:00
Prader-Willi Syndrome Overview 00:34
Current Management 1:48
Vykat (Diazoxide Choline) Overview 2:38
Phase 3 Clinical Trial 4:06
Take Home Message 7:37

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Aravindhan Veerapandiyan, MD, Assistant Professor of Pediatrics, University of Arkansas and Arkansas Children’s Hospital, discusses results from the phase 1/2 EXPLORE44 clinical trial for Duchenne muscular dystrophy (DMD).

DMD affects the muscles, leading to progressive muscle wasting. 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 muscle. 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.

Del-zota is a part of a new class of RNA therapeutics called antibody oligonucleotide conjugates (AOCs). It is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal and cardiac muscle tissues. This targets the skipping of exon 44 of the dystrophin gene and enables production of near-full length dystrophin.

The phase 1/2 EXPLORE44 clinical trial is a randomized, double-blind, placebo-controlled, study evaluating the efficacy, safety, and tolerability of del-zota in two dose levels of 5 mg/kg and 10 mg/kg.

From the recent data, targeted delivery of PMOs resulting in approximately 200nM tissue concentrations in skeletal muscle were observed. There was also a statistically significant increase of about 40% in exon 44 skipping, and an increase of about 25% of normal dystrophin production and restored total dystrophin up to 58% of normal. Additionally, a reduction in creatine kinase levels to near normal with greater than 80% reductions compared to baseline were observed.

Additionally, patients originally treated with placebo demonstrated a reduction of creatine kinase levels to near normal upon treatment with del-zota. Significant reductions were also seen in the EXPLORE 44 open label expansion with continued treatment up to one year.

Finally, del-zota illustrated a favorable safety and tolerability profile with the majority of treatment emergent adverse events being mild or moderate. The results from this study were consistent in all parameters for both the 5 mg/kg and 10 mg/kg groups.

Chapters:
Introduction
DMD Overview and Exon Skipping
EXPLORE44 Clinical Trial
Take Home Message
Next Steps
What Physicians Should Know
Addressing Unmet Needs

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