Phioanh Leia Nghiemphu, MD, Professor of Clinical Neurology at University of California Los Angeles, discusses the use of mirdametinib for neurofibromatosis type 1 with symptomatic plexiform neurofibromas (NF1-PN).


NF1 is a genetic condition that affects the skin, skeleton, and peripheral nervous system. The main signs and symptoms of NF1 include dark colored spots on the skin, neurofibromas, and freckles in the underarm and groin. Other symptoms may include colored spots in the eye, curvature of the spine, learning disabilities, and an increased risk for cancer. Plexiform neurofibromas are benign tumors that develop on or around neurons. The number of neurofibromas typically increases over time, and some can get large or turn cancerous and need to be removed. This condition is caused by genetic changes in the NF1 gene.

Earlier this year, the U.S. Food and Drug Administration (FDA) approved mirdametinib for the treatment of adult and pediatric patients ages 2 years and older with NF1 who have symptomatic plexiform neurofibromas (PN). Mirdametinib is an oral, small molecule, MEK inhibitor. It is the first and only FDA-approved therapy for this indication. Miradametinib received an accelerated approval based on results from the phase 2b ReNeu trial.

The study enrolled 114 patients with NF1-PN two years of age and older. Dr. Nghiemphu explains that the primary endpoint of the study, confirmed objective response rate (ORR), was met with a 41% ORR in adults and 52% in children. Tumor volume reductions were also significant and durable. Additionally, patients experienced reductions from baseline in pain and quality of life.

The safety and tolerability profile of mirdametinib was favorable with the most common adverse events in adults including rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. The most common adverse events in pediatric patients included rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.

Chapters:
Introduction 00:00
NF1-PN Overview 00:31
Presentation and Diagnosis 3:04
Mirdametinib Overview 4:04
Similarity to RASopathies 4:59
ReNeu Clinical Trial 5:24
Specialty Clinics 7:50
What Physicians Should Know 10:06

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Shaishav Dhage, MD, Endocrinologist at The Christie Hospital, discusses a case report on a patient with alemtuzumab-induced thyroid eye disease (TED).

TED is a rare autoimmune disease that can dramatically impact a person’s vision. The condition often occurs in people with hyperthyroidism or Graves’ disease (GD), but also can occur in association with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis. GD affects approximately 1% to 2% of the adult population, with an estimated 40% of GD patients subsequently developing TED over the course of their lifetime. The onset of TED typically occurs between 30 and 50 years of age, with the disease course more severe after age 50. Common symptoms can include upper eyelid retraction, dry eyes, inflammation, light sensitivity, as well as the sensation of a foreign body present in the eye.

Alemtuzumab is a humanized monoclonal antibody that targets CD52 glycoprotein found on most mature leukocytes. The treatment is used in patients with relapsing/remitting multiple sclerosis. Due to its immunomodulatory effects, however, it is commonly associated with secondary autoimmunity. Although not frequently observed, alemtuzumab-induced TED (AI-TED) is a possible secondary autoimmunity. It is caused by antibody-mediated activation of the thyroid-stimulating hormone receptor in orbital tissues.

Two patients were reviewed who developed AI-TED between one to three years after treatment. The average clinical activity score on presentation was 3/7, which was also the peak score during the active phase of disease. Both patients were treated with lubricant eye drops, selenium, and intravenous methylprednisolone. One patient also required mycophenolate mofetil and azathioprine as second-line therapy before remission was achieved.

The review highlights that as the use of alemtuzumab increases in the management of MS, the incidence of AI-TED is likely to also increase. AI-TED can develop several years following treatment, requiring careful attention for timely diagnosis, especially in mild cases. The potential for significant morbidity in moderate to severe TED emphasizes the importance of early recognition, diagnosis, and appropriate treatment.

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Jui-En Lo, MD, Resident of Internal Medicine at MetroHealth, discusses trends and social determinants of teprotumumab in thyroid eye disease (TED).

TED is a rare autoimmune disease that can dramatically impact a person’s vision. The condition often occurs in people with hyperthyroidism or Graves’ disease (GD), but also can occur in association with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis. GD affects approximately 1% to 2% of the adult population, with an estimated 40% of GD patients subsequently developing TED over the course of their lifetime. The onset of TED typically occurs between 30 and 50 years of age, with the disease course more severe after age 50. Common symptoms can include upper eyelid retraction, dry eyes, inflammation, light sensitivity, as well as the sensation of a foreign body present in the eye.

Teprotumumab is a monoclonal antibody that targets the insulin-like growth factor-1 receptor (IGF-1R), inhibiting orbital fibroblast activation. It was approved for treatment of TED by the U.S. Food and Drug Administration (FDA) in 2020. A study presented at the ENDO 2025 meeting examined treatment trends for TED and explored clinical and demographic factors of prescribing teprotumumab. The study was retrospective and observational and included 100,000 patients with hyperthyroidism between 2018 and 2024.

Of these 100,000 patients, over 200 received teprotumumab annually, with a peak in 2021 following the FDA approval. Additionally, the number of patients undergoing orbital decompression significantly dropped after 2020. Glucocorticoid use remained relatively stable compared to the number of patients with hyperthyroidism.

Multivariable Cox regression showed that White patients were significantly more likely to receive teprotumumab than non-White patients. Specifically, Black and Asian patients were significantly less likely to receive the treatment compared to White patients but Hispanic or Latino ethnicity was not significantly associated with use of teprotumumab. Additionally, patients with low socioeconomic status were significantly less likely to receive teprotumumab.

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Margarita Ochoa-Maya, MD, Medical Director of the Rare Disease Business Unit at Amgen, discusses the TEDucation campaign for thyroid eye disease (TED).

TED is a rare autoimmune disease that can dramatically impact a person’s vision. The condition often occurs in people with hyperthyroidism or Graves’ disease (GD), but also can occur in association with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis. GD affects approximately 1% to 2% of the adult population, with an estimated 40% of GD patients subsequently developing TED over the course of their lifetime. The onset of TED typically occurs between 30 and 50 years of age, with the disease course more severe after age 50. Common symptoms can include upper eyelid retraction, dry eyes, inflammation, light sensitivity, as well as the sensation of a foreign body present in the eye.

The Amgen TEDucation campaign is an educational initiative for endocrinologists to learn more about TED so that it can be better identified, diagnosed, and treated proactively. The campaign utilizes games and guest speakers to engage endocrinologists while identifying gaps in care and giving physicians the tools they need to open up conversation with their patients.

Dr. Ochoa-Maya explains how the recent meeting identified the need for educating endocrinologists in their understanding of the American Thyroid Association and European Thyroid Association consensus of their role in identifying TED.

Chapters:
Introduction 00:00
Thyroid Eye Disease Overview 00:23
Diagnosis 1:04
Amgen Campaign Overview 2:08
Red Flags of Thyroid Eye Disease 4:05

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Jack Johnson, Co-Founder and Executive Director of FSIG, discusses symptom and treatment burden in Fabry disease.

Fabry disease is a rare lysosomal storage disease characterized by a deficiency in the enzyme alpha-galactosidase (alpha-GAL). Alpha-GAL helps break down a fatty acid called globotriaosylceramide (GL3). Symptoms of Fabry disease may include episodes of pain, especially in the hands and feet, clusters of small angiokeratomas, hypohidrosis, corneal opacity, and hearing loss. Internal organs, such as the kidney, heart or brain, may also be affected, leading to progressive kidney damage, heart attacks, and strokes. Fabry disease is caused by changes in the GLA gene.

Mr. Johnson explains that the most burdensome symptoms for patients with Fabry disease are typically those that are difficult to measure, and therefore manage. This most notably includes pain, fatigue, inadequate temperature regulation, and gastrointestinal issues. While these symptoms cannot be measured through medical tests, they are often measured via patient reported outcome surveys.

Alternatively, health care practitioners tend to focus on symptoms that can be measured through imaging or blood and urine testing. The focus on these components of Fabry disease can be frustrating to patients who may not experience effect on daily life due to these symptoms. However, Mr. Johnson notes the importance of these tests in addressing issues early on before they become bigger problems that do affect a patient’s daily life.

An additional burden for patients with Fabry disease is the burden of treatment with enzyme replacement therapy. Many patients with Fabry disease receive transfusions once every two weeks, greatly impacting daily activities such as school and work. This can also make travel difficult as patients have to plan around their transfusion appointments, with some patients noticing changes in symptoms if an appointment is off by even just one day. Initiation of therapy can also pose challenges such as not noticing any effects up to 6 months to one year after. This causes many patients to discontinue treatment and only return when medically necessary.

Because of such great burdens of symptoms and treatment in Fabry disease, patients are hopeful for advancements that address these unmet needs. Mr. Johnson discusses the hopes of patients for a new therapy that would reduce the number of infusions per year or even for a one-time gene therapy.

Chapters:
Introduction 00:00
Fabry Disease Overview 00:22
Most Burdensome Symptoms 00:51
Symptoms That Physicians Focus On 4:10
Tracking Patient Reported Outcomes 5:38
Treatment Burden 6:07
Emerging Clinical Trials and Treatment 9:04
FSIG Meetings 10:23

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Jonathan Strober, MD, Director of the Neuromuscular Clinic and Professor of Pediatrics and Neurology at the University of California at San Francisco, discusses the implications of nipocalimab's approval to treat pediatric 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 U.S. Food and Drug Administration (FDA) recently approved Imaavy (nipocalimab) for the treatment of generalized MG in patients ages 12 years and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibody positive. Nipocalimab is a human monoclonal antibody FcRn-inhibitor designed to reduce immunoglobulin G (IgG) autoantibodies.

The approval was supported by data from the Vivacity-MG3 clinical trial (NCT04951622). The study illustrated superior disease control through 24 weeks, measured by MG Activities of Daily Living score, in patients treated with nipocalimab plus standard of care versus those treated with placebo plus standard of care. A rapid and sustained reduction in autoantibody levels by up to 75% from the first dose and throughout a 24-week period of monitoring was also observed. Additionally, improvements in patients treated with nipocalimab plus standard of care were maintained out to 20 months of follow-up in the open-label extension.

In addition to the above study, nipocalimab is also being tested in patients as young as 2 years of age. Results from the ongoing Vibrance phase 2/3 pediatric study (NCT05265273), patients aged 2 to 17 years, showed that nipocalimab plus standard of care met its primary endpoint with a 69% reduction in total serum IgG over 24 weeks. Improvements were also seen in MG Activities of Daily Living and Quantitative MG scores. The safety profile of nipocalimab has been favorable and consistent across both studies.

Chapters:
Introduction 00:00
MG Treatment Landscape 00:42
Nipocalimab Overview 2:48
Vivacity-MG3 Clinical Trial 3:38
Implications for Physicians 4:07

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