Lena Specht, MD, DMSc, Professor of Clinical Oncology, and Chief Oncologist at Rigshopitalet, University of Copenhagen, Denmark, discusses her Danish study supporting the use of mogamulizumab in Danish patients with CTCL.

Mogamulizumab was approved in 2018 in Europe based on the results of the MAVORIC trial, which was a randomized study comparing progression-free survival outcomes against vorinostat, an FDA-approved treatment, in patients with CTCL.

Vorinostat was never approved in Europe, because it was associated with data issues and was not considered a valid study comparator. As a result, the Danish regulatory authorities approved mogamulizumab for use only after a trial of one prior line of systemic chemotherapy. In comparison, the US FDA approved mogamulizumab for use as first-line treatment of CTCL.

Dr. Specht’s group of researchers attempted to compare the randomized phase 3 trial comparing mogamulizumab and the Danish standard of care by utilizing the MAVORIC study data along with data from a real-world registry of Danish patients with CTCL from 1996 to 2024. They selected comparator patients from the registry according to MAVORIC inclusion criteria (including patients with either myocosis fungoides or Sézary syndrome who failed at least one line of systemic therapy). In addition, they evaluated data from the vorinostat arm in MAVORIC (i.e., those patients who did not switch over to mogamulizumab therapy).

The main outcome of interest was overall survival. They found overall survival to be longer (with a statistically significant difference) for those receiving mogamulizumab first line compared with the Danish patients with CTCL in the real-world registry. Although making treatment comparisons using nonrandomized patient data is problematic, Dr. Specht and her researchers were reassured that there was not any significant difference in the outcomes of those in the vorinostat treatment arm of MAVORIC and in the Danish registry population receiving standard of care.

Normally, Sézary syndrome is very difficult to treat, but mogamulizumab seems to work better in these patients than in those with mycosis fungoides, which is generally considered a less-aggressive cancer. According to Dr. Specht, this is a strong argument for first-line access to mogamulizumab in patients with Sézary syndrome.

CHAPTERS
Introduction 00:00
Mogamulizumab Clinical Trial 00:58
Key Findings in Overall Survival 3:15
Patient Subgroup Analysis 4:29
Key Takeaway 6:11

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This educational program, hosted by Dawn Laney, MS, CGC, CCRC, Genetic Counselor and Program Leader for the Lysosomal Storage Disease Center at Emory University, and Staci Kallish, DO, Associate Professor of Clinical Medicine in the Division of Translational Medicine and Human Genetics at the University of Pennsylvania, examines how best to respond to patients concerns about how their Fabry disease, and its comorbidities, are managed. This program features a dialogue between patients who express their unmet needs, while two renowned Fabry disease experts translate these challenges into actionable clinical strategies.

Topics covered include 1) symptoms that patients believe are not being well managed by their medical team, 2) whether the risk of stroke or heart failure is being properly addressed by medical teams, 3) whether the risk of kidney failure is being properly addressed by medical teams, and 4) how well the medical team works together and understands Fabry disease.

This educational program is a non-CME activity made possible by an unrestricted grant from Amicus Therapeutics


Faculty
Dawn Laney, MS, CGC, CCRC
Genetic Counselor, Division of Medical Genetics
Program Leader, Lysosomal Storage Disease Center
Emory University School of Medicine
Disclosures
Consulting agreements: Amicus Therapeutics, Chiesi, Sanofi
Member: North American and International Fabry Registry Boards

Staci Kallish, DO
Associate Professor of Clinical Medicine
Division of Translational Medicine and Human Genetics
Perelman School of Medicine, University of Pennsylvania
Disclosures
Research grants: ashibio, Astellas Pharma, , Amicus Therapeutics
Idorsia Therapeutics, Incyte , Ipsen, and Sanofi
Consulting: Amicus Therapeutics, Sanofi
Advisory board: Amicus Therapeutics, Intrabio, Sanofi
Speaking honoraria: Amicus Therapeutics, Astellas, Sanofi

Learning Objectives
Upon completion of this program, participants will be able to:
• Recognize the real-world burdens facing Fabry patients and implement strategies to alleviate them.
• Identify and overcome barriers to managing heart concerns in patients with Fabry disease.
• Identify and overcome barriers to managing kidney concerns in patients with Fabry disease.
• Orchestrate a cohesive, multidisciplinary team approach to care.

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My name is Dr. Joshua Zeidner, and I’m a Professor of Medicine and Chief of Leukemia Research at the University of North Carolina Lineberger Cancer Center. I’m here today to raise awareness around an active global, phase 3, double-blind trial evaluating a combination regimen for participants with a specific type of acute myeloid leukemia or AML.

Disclaimer: This material is intended for healthcare practitioners only. This use of Revumenib is under investigation and has not been approved by the FDA or any other regulatory agency worldwide. No conclusions of safety or efficacy can be drawn. Patient eligibility criteria apply.

1. Can you describe the REVEAL-Newly Diagnosed NPM1m trial?
The REVEAL-ND NPM1m trial is evaluating whether the addition of revumenib, a menin inhibitor, to standard chemotherapy improves outcomes in newly diagnosed patients with NPM1-mutated AML compared with chemotherapy alone. It is a global, phase 3, double-blind, trial in which participants will be randomized to receive standard intravenous chemotherapy with either oral revumenib or placebo.

2. What is the trial evaluating?
The trial is designed to assess whether this combination improves key clinical outcomes. The dual primary endpoints are event-free survival and measurable residual disease -negative complete response rate in the bone marrow. A key secondary endpoint is overall survival. Other secondary endpoints include overall response rate, complete response rate, composite complete remission, duration of response, safety and tolerability, and patient-reported fatigue.

3. What is the study design?
Participants are randomized 1:1 to receive oral revumenib 270 mg Q12 without a strong CYP3A4 inhibitor or revumenib 160 mg Q12 with a strong CYP3A4 inhibitor or placebo in combination with intensive chemotherapy during Induction and Consolidation followed by Maintenance. Intensive chemotherapy consists of cytarabine and daunorubicin or idarubicin in the Induction Phase and cytarabine alone in the Consolidation Phase. The Maintenance Phase will consist of revumenib or placebo given twice daily as monotherapy. Oral revumenib or placebo administration will continue for up to 2 years from Induction Cycle 1 Day 1. Bone marrow aspirates/biopsies will be collected to assess response. Participants may undergo hematopoietic stem cell transplant after initial induction chemotherapy or after consolidation and may resume maintenance thereafter.

4. Who is eligible for the trial?
Individuals from all backgrounds and communities are welcome to take part in the trial. Participants may be eligible if they have newly diagnosed, previously untreated, centrally confirmed NPM1 mutated AML and are eligible to receive intensive chemotherapy. Adolescents and adults ≥12 years of age are eligible. Participants must have adequate liver, kidney, and cardiac function.
Key exclusions include pregnancy or breastfeeding, active acute promyelocytic leukemia, active central nervous system (CNS) disease, gastrointestinal (GI) disease that affects drug absorption or indigestion, AML with FLT3-ITD mutation with a variant allele frequency of ≥5%, or if FLT3 inhibitor use is indicated.

5. Where is REVEAL-ND NPM1m enrolling?
The trial plans to enroll approximately 468 patients globally. Recruitment is planned across North America, Latin America, Europe, the Middle East, and the Asia-Pacific region.

6. If our viewers have participants who would potentially benefit from participating in the REVEAL-ND trial, how should they inquire about study enrollment?
The study has an Email address for potential participant enrollment: [email protected].

7. How about if a hospital/healthcare organization would like to participate in the REVEAL-ND trial?
The center should contact the study managers, through the same Email address: [email protected].

Use of revumenib in this setting is investigational and is not approved for this use by the FDA or any health authority worldwide.

References:
https://clinicaltrials.gov/study/NCT07211958#study-plan
Stein E, Issa G, Rego E, et al. A Phase 3 Study of Revumenib in Combination With Intensive Chemotherapy in Patients With Newly Diagnosed NPM1-Mutated Acute Myeloid Leukemia (REVEAL- ND NPM1): Trial in Progress. TPS6602 Poster presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL

Disclaimer: This presentation is sponsored by Syndax. The speaker is being compensated by Syndax for his time and participation in this presentation. The information contained herein is intended solely for educational and informational purposes © 2026 Syndax Pharmaceuticals, Inc. All rights reserved. MED-REV-260086 09/2026.

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Spinal muscular atrophy (SMA) has undergone a remarkable transformation over the past decade. Drs. Nancy Kuntz, Alicia Henriquez, and Angela Lek discuss how advances in disease-modifying therapies have fundamentally changed the outlook for children living with SMA, leading clinicians to rethink what constitutes a successful outcome in SMA care.

Over the past decade, the management and treatment of spinal muscular atrophy (SMA) have been transformed, resulting in remarkable effects on young patients’ neuromuscular function status, mobility, and quality of life. These improvements would have been difficult to imagine just a few years ago and challenge clinicians, researchers, patients, and families to rethink what is defined as a successful outcome in SMA care.

According to Nancy Kuntz, MD, a child neuromuscular specialist from Lurie Children’s Hospital, Chicago, when before the use of newborn screening and the latest treatments, the main outcome of interest was prolonged patient survival. Today, achievable patient outcomes include sitting upright, and walking independently. This is a long way from the palliative view of SMA care. The use of standard measurement scales of patient outcomes need to keep up with evolving expectations of caregivers and patients.

This will require objective data, like biomarkers, x-ray changes, and the ability to see significant changes in motor scale scores, focused on types of motor function that is important to patients. Alicia Henriquez, MD, a pediatric neuromuscular specialist from Seattle Children’s Hospital, pointed to one of the standard functional scales used in therapeutic clinical trials, the Hammersmith Functional Motor Scale Expanded (HFMSE). It is based on 33 distinct functional domains, but not all of those domains are of equal importance to patients and caregivers. And a change in HFMSE scale measurement may not be statistically significant for the purposes of clinical trials, but that incremental change in one domain may be highly important for the individual. The scales do a better job of detecting major changes in function but not what those changes mean for patients.

The Muscular Dystrophy Association (MDA) is helping to bring more light to this issue. Angela Lek, PhD, Chief Research Officer at the Association, described how MDA is sponsoring registry studies to collect real-world outcomes of individuals with SMA. This may result in patient-reported measures that may more-directly reflect improvements that patients believe are important.

CHAPTERS
Introduction 00:00
Can Current Outcome Measures Keep Up? 1:10
The Functional Improvements That Matter Most 22:16
The Patient Perspective and Road Ahead 34:19

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Stacey Kallish, MD, Clinical Geneticist at Penn Medicine in Philadelphia, is helping to lead a new wave of innovation at the intersection of artificial intelligence (AI) and rare disease care. With a clinical focus on lysosomal storage diseases (LSDs)—including Fabry disease, Gaucher disease, and Pompe disease—Dr. Kallish is exploring how emerging technologies can improve diagnosis, risk prediction, and long-term management for patients with complex genetic conditions.

AI is increasingly becoming a topic of discussion across healthcare, but in rare diseases, its potential impact may be especially significant. These conditions are often difficult to recognize due to their rarity, variability, and overlap with more common disorders. As a result, patients frequently experience delayed or missed diagnoses. AI offers a powerful opportunity to change that.

By training machine learning models on datasets of patients with confirmed rare diseases, researchers can teach these systems to recognize patterns that distinguish affected individuals from those without disease. These models can then be applied to large-scale datasets, such as electronic health records (EHRs), to flag patients who may otherwise go undiagnosed.
Dr. Kallish explains that one of AI’s greatest strengths lies in its ability to synthesize vast amounts of information. “These models can evaluate countless small data points simultaneously—far more than we can realistically process as clinicians,” she notes. This allows AI to detect subtle signals that may not be immediately apparent, particularly in early or atypical cases.

Beyond diagnosis, AI is also being investigated as a tool for predicting disease progression and guiding treatment decisions. In conditions like Fabry disease, clinicians must often determine when to initiate therapy and how to assess a patient’s risk for complications such as stroke or organ damage. AI-driven models have the potential to analyze longitudinal patient data and generate individualized risk profiles, offering more precise and personalized insights.
However, while these applications are promising, Dr. Kallish emphasizes that the field is still evolving. Diagnostic use cases—such as identifying patients through EHR screening or interpreting genetic variants—are likely to reach clinical utility sooner. More complex applications, like optimizing treatment timing or selecting the most appropriate therapy for an individual patient, will require additional validation and real-world evidence.

Importantly, AI is not intended to replace physicians. Instead, it is best understood as a complementary tool—one that can enhance clinical decision-making and improve access to specialized expertise. This is particularly evident in the field of medical imaging.
Studies have shown that AI models can perform at a level comparable to expert radiologists in interpreting imaging studies such as brain MRIs. In some cases, these models even outperform general radiologists. But rather than viewing this as a threat, Dr. Kallish sees it as an opportunity for collaboration.

“The goal is partnership,” she explains. “AI can help us get to better answers, especially in settings where specialized expertise may not be readily available.” For patients in community hospitals or underserved areas, this could mean more accurate diagnoses and improved care without the need for referral to major academic centers.

Another area where AI may have a transformative impact is biomarker development. Currently, clinicians rely on a combination of enzyme assays, molecular testing, and established biomarkers to diagnose and monitor LSDs. AI has the potential to identify new biomarkers that are more sensitive, more specific, and potentially tailored to individual patients. These insights could help clinicians better determine when to initiate treatment, assess disease progression, and evaluate therapeutic response.

Some AI-driven tools are already making their way into clinical practice. One example is FDrisk, a publicly available platform that uses machine learning to estimate the likelihood of Fabry disease based on a series of clinical inputs. By answering a set of targeted questions, clinicians can generate a dynamic risk score and receive guidance on next steps, including whether to pursue diagnostic testing.

At a broader level, researchers are also leveraging AI to analyze patient journeys within healthcare systems. By studying the clinical trajectories of patients with known rare diseases, machine learning models can identify similar patterns in other patients’ records. This approach has already demonstrated success in detecting conditions such as Rett syndrome and Lowe syndrome, highlighting the potential for earlier identification and intervention.

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Merlin G. Butler, MD, Medical Geneticist and Professor, Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, and one of the pioneers in Prader–Willi syndrome research, discusses the clinical features of this very rare disease and the critical importance of early identification.

Prader–Willi syndrome was first reported in 1956, and deletions in chromosome 15 were first identified in the 1980s. Dr. Butler has been working on the genetics of Prader–Willi syndrome since that decade.

Dr. Butler said that Prader–Willi syndrome was the first example of a disorder caused by “genetic imprinting,” in which it matters whether genes are contributed by the mother or the father. In 70% of the cases of this disorder, the father’s contribution is missing from chromosome 15q13, and 25% of cases are the result of both copies of chromosome 15 being from the mother (referred to as “disomy”).

Babies born with this genetic anomaly have severe hypotonia, and they have no interest in sucking or feeding. They often have decreased muscle mass and energy. “These infants look like they have a major problem at birth,” stated Dr. Butler. They need to be tube-fed. Once a genetic cause is suspected, Prader-Willi syndrome is quickly diagnosed; it is a very rare disease that also has very unique features. Pediatricians may see only one of these patients every 10 years. Therefore, according to Dr. Butler, “it is the parents who oftentimes make the diagnosis, through what they have seen on the Internet, prompting genetic testing.”

Despite their problems with feeding in the neonatal period, infants with Prader–Willi syndrome will begin to gain an interest in feeding by around age 2 to 3 years. By age 6 years, they develop hyperphasia. “Once their appetite is turned on,” he said, “it is never off.” Uncontrolled, this results in obesity and life-threatening conditions, such as type 2 diabetes and stomach rupture.

Early identification is key, and determining the genetic subtype is extremely important to building a multidisciplinary care team. There are seven different genetic subtypes, which can impact outcomes and management. Typically, the care team will include the medical geneticist and genetic counselors, endocrinologists (to manage the use of growth hormone and diabetes-related treatment), dietitians to manage and monitor caloric intake, mental health experts to address behavioral issues and the risk of self-injury, gastroenterologists, and potentially even sleep medicine professionals. The specialists comprising the care team will change over the patient’s lifespan; occupational therapy and speech therapy may well be required as the patient ages.

The treatment of hyperphagia associated with Prader–Willi syndrome, the number 1 issue, is a particularly active area of research. The idea is to avoid the onset of obesity, which can lead to most of the comorbidities and complications.

CHAPTERS
Introduction 00:00
Prader-Willi Syndrome Overview 00:48
Diagnostic Odyssey 6:30
Multidisciplinary Approach to Management 8:42
Emerging Therapies and Research 10:21
Key Message for Clinicians 11:58
Advice for Newly Diagnosed Families 17:37

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Robert Rapaport, MD, Professor of Pediatric Endocrinology, and Director of the Comprehensive Growth Center at the Icahn School of Medicine, Mount Sinai Medical Center, New York City, discussed the differences between severe, primary IGF-1 deficiency and growth hormone (GH) deficiency in patients with short stature.

In young patients with short stature, GH deficiency is the most common cause. However, in a small subset of patients, the underlying problem is not GH deficiency but an abnormality in insulin-like growth factor-1 (IGF-1) levels. This peptide hormone was first discovered 50 years ago, and IGF-1 deficiency has been found to be caused by mutations in the GH receptor and defects in the IGF-1 gene. In patients with a specific subtype of severe, primary IGF-1 deficiency (SPIGF1D) called Laron syndrome, the specific cause is GH-receptor mutations.

Severe, primary IGF-1 deficiency is generally associated with the following patient characteristics: severe postnatal growth failure, short limb length, typical facial features (e.g., small forehead), and delays in sexual development and skeletal maturation. Crucially, affected children do not respond to a GH stimulation test.

Patients who have abnormally low GH levels can also be considered IGF-1 deficient. On the other hand, if the patient has normal GH levels, IGF-1 concentrations may still be abnormally low. According to Dr. Rapaport, patients with IGF-1 deficiency may be found to have abnormal IGF-1 levels across a spectrum from borderline low to extremely low, the latter of which represents the main feature of SPIGF1D (IGF-1 levels are 5–6 standard deviations below the mean for healthy individuals).

The only effective treatment for SPIGF1D is IGF-1 supplementation, with mecasermin, a human recombinant IGF-1 preparation. Although mecasermin is proven to increase patients’ growth velocity, patients taking the product are expected to attain “near normal” adult height only. It is given twice daily, and it does carry a risk of hypoglycemia, as IGF-1 lowers blood glucose levels. It is thus important that patients and their caregivers are well educated about avoiding this dangerous adverse effect.

CHAPTERS
Introduction 00:00
Primary IGF-1 Deficiency Overview 00:44
Severe IGF-1 Deficiency 3:32
Diagnosis in Children 4:42
Treatment for Severe IGF-1 Deficiency 5:29
Safety Considerations 8:07
Unmet Needs 8:56
Take Home Message 9:36

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