Guy Young, MD, Director of the Hemostasis and Thrombosis Program at Children's Hospital Los Angeles, discusses an ATLAS-OLE subgroup analysis of fitusiran in patients with hemophilia.

Hemophilia is a rare 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. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. The major types of this disorder are hemophilia A and hemophilia B, caused by a deficiency of factor VIII and IX, respectively.

Fitusiran is the first antithrombin (AT)-lowering therapy approved by the FDA for the treatment of patients ages 12 years and older with hemophilia A and B, with or without factor VII or IX inhibitors. Fitusiran is a small interference RNA drug that inhibits antithrombin and promotes thrombin generation, restoring homeostasis and increasing blood clotting. It is administered subcutaneously with a 50mg dose.

A study presented at the 2026 International Society on Thrombosis and Haemostasis (ISTH) Congress aimed to assess the safety and efficacy of fitusiran AT-DR in a subgroup analysis by age group from the phase 3 open-label extension study ATLAS-OLE (NCT03754790).


A total of 286 males aged 12 years and older with severe hemophilia A and B, with and without inhibitors, received the AT-DR and were included in the safety analysis. The proportion of participants with any treatment-emergent (TEAEs) and serious adverse events were similar, irrespective of age. There were no treatment discontinuations due to TEAEs in the adolescent population. One of 60 adolescents, three of 266 adults and none of the three elderly participants experienced a thrombotic event. Additionally, no transaminase elevations greater than 3x ULN were reported in adolescents.


Efficacy analyses included 213 participants. Observed median annualized bleeding rate (ABR) were 3.7 in the adolescent population and 3.7 in both the adult and overall populations. A total of 40% of adolescents had no bleeds compared to 28.9% of adults. ABR and number of bleeds were significantly lower in the elderly population. However, it is noted that the sample size remains too small to support definitive conclusions.

CHAPTERS
Introduction 00:00
ATLAS-OLE Results 00:19
Fitusiran as a Long-Term Treatment Option 3:39
Addressing Gallbladder Issues 6:20
Hemophilia Indications 7:58

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Caterina Garone, PhD, MD, Associate Professor at the University of Bologna, discusses the summary of safety and efficacy data on Kygevvi (doxecitine and doxribtimine) in patients with thymidine kinase 2 deficiency (TK2d).

TK2d is a rare genetic disease characterized by progressive and severe muscle weakness. It is often fatal. Patients who develop symptoms before the age of 12 years tend to show rapid disease progression and are at high risk of premature death. Other common symptoms include breathing difficulties, weakness in the eye muscles, and trouble chewing and swallowing. TK2d is caused by genetic mutations in the TK2 gene.

Kygevvi is a combination of two pyrimidine nucleosides, doxecitine and doxribtimine, that target and restore mitochondrial DNA in the skeletal muscle. It is the first and only treatment, approved by the U.S. Food and Drug Administration (FDA) in November 2025, for patients with TK2d.

New data published in Brain Communications examines the safety and efficacy of Kygevvi in TK2d and highlights the progressive disease burden in untreated patients.

Safety and efficacy data were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) studies and expanded access programs of patients treated with Kygevvi. Untreated patients were pooled from literature reviews and a retrospective chart review study (NCT05017818).

A total of 218 patients were included (104 treated; 114 untreated) and most patients had an age of symptom onset at or before 12 years. In the age-of-symptom-onset-12-years-or-earlier subgroup, restricted mean survival time was 29.2 years over the 30 years after symptom onset for treated patients and 14.4 years for untreated patients.

Loss of 1 or more acquired motor milestones was more frequent before treatment start than after. Substantially more patients regained 1 or more lost motor milestone after treatment start than before. Ventilatory and feeding support were used across all age-of-symptom-onset subgroups, but some patients reduced or discontinued support after starting treatment and fewer patients initiated support after treatment start than before.

Most treatment-emergent adverse events (AEs) did not lead to discontinuation. The most frequent AE was diarrhoea, which was generally mild or moderate and resolved with dose reduction. Serious AEs occurred in 56% of patients and 8% were considered to be drug related. In total, three patients experienced a fatal serious AE, which were not considered to be drug related.

CHAPTERS
Introduction 00:00
Thymidine Kinase 2 Deficiency Overview 1:48
Effect of Kygevvi on Survival 4:52
Importance of Early Diagnosis 7:02
Key Takeaways for Clinicians 9:01
Remaining Challenges 10:25

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Doug Kerr, MD, PhD, MBA, Chief Medical Officer of Dyne Therapeutics, discusses the initiation of the phase 3 FORZETTO trial of zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251), in individuals with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping.

DMD is a rare genetic, neuromuscular condition characterized by progressive muscle wasting. 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 DMD gene.

Z-rostudirsen is an investigational therapeutic consisting of a phosphorodiamidate morpholino oligomer (PMO) conjugated to an antigen-binding fragment (Fab) that binds to the transferrin receptor 1 (TfR1). It is designed to enable the production of near full-length dystrophin in muscle and the central nervous system to provide functional improvement.

The design of the FORZETTO clinical trial was presented at the 2026 International Congress on Neuromuscular Diseases (ICNMD).

FORZETTO is a global, randomized, placebo-controlled, double-blind, confirmatory phase 3 trial designed to assess the efficacy, safety, and tolerability of z-rostudirsen administered intravenously to ambulatory male participants with DMD amenable to exon 51 skipping. The trial will enroll approximately 90 participants ages 4 to 18 years who will be randomized to receive 20 mg/kg of z-rostudirsen or placebo every four weeks. The first trial site is activated and open to enrollment.

The primary endpoint is the change from baseline to week 83 in rise from floor (RFF) velocity, or time to rise (TTR) velocity, a clinically meaningful measure of muscle strength and motor coordination. Secondary endpoints include changes from baseline in stride velocity 95th centile, North Star Ambulatory Assessment total score, 10-meter walk/run velocity, four-stair climb velocity and forced vital capacity percent predicted. Following the 72-week double-blind placebo-controlled treatment period, participants will be eligible to enroll in a 96-week open-label long-term extension.

CHAPTERS
Introduction 00:00
DMD Overview 00:16
The DMD Gene 1:18
Therapy Development 3:08
FDA Submission 5:05
Age Range Effectiveness 8:38
Extent of Treating Patients 11:08
What Physicians Should Know 13:26

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Priya Kishnani, MD, Professor and Chief of the Division of Medical Genetics at Duke University, discusses the GALILEO-3 clinical trial of FLT201 in adults with Gaucher disease type 1 (GD1).

GD1 is the most common form of Gaucher disease. It is caused by a deficiency of glucocerebrosidase (GBA), an important enzyme that breaks down a fatty chemical called glucocerebroside. Because the body cannot break down this chemical, fat-filled Gaucher cells build up in areas like the spleen, liver and bone marrow. Unlike type 2 and 3, GD1 does not usually involve the central nervous system. Symptoms of GD1 include enlarged spleen and liver, low blood cell counts, bleeding problems and bone disease. Gaucher disease is caused by changes in the GBA gene.

It was recently announced that the first patient has been dosed in the GALILEO-3 clinical trial (NCT07223944). This study is a phase 3 non-randomized, global, multicenter study evaluating the safety and efficacy of FLT201in adult patients with GD1 currently on stable standard-of-care therapies.

The study hopes to enroll approximately 45 adults with GD1 who have been stable on enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) for at least two years. Participants will receive a single intravenous infusion of FLT201 alongside a prophylactic immunosuppressive regimen.

The primary endpoint is the proportion of participants maintaining stable hemoglobin concentration at week 52. Secondary endpoints include safety and tolerability, stability of platelet counts, spleen and liver volumes, biomarker changes, bone marrow burden and mineral density changes, and patient-reported quality-of-life outcomes.

FLT201 is a proprietary, liver-tropic capsid and an engineered beta-glucocerebrosidase (GCase85), designed to deliver continuous, sustained enzyme exposure beyond what is achievable with ERT. This allows for a low vector genome dose, necessary for a favorable safety profile. FLT201 has both Orphan Drug and RMAT (regenerative medicine advanced therapy) designations from the FDA.

Clinical trial eligibility is as follows:

Key Inclusion Criteria:
Aged ≥18 years at time of screening.
Clinical diagnosis of Gaucher disease type 1
Stable hemoglobin concentration at baseline
Stable platelet count at baseline
Receiving ERT or SRT without interruption for at least 2 years

Key Exclusion Criteria:
Diagnosed or suspected Gaucher disease type 2 or type 3
Positive for AAVS3 neutralizing antibodies.
Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study
Positive pregnancy test or lactating
History of hematopoietic stem cell transplant (HSCT)/bone marrow transplant or any solid organ transplant.
History of receiving any gene therapy or cell therapy.
History of total splenectomy. Note: Additional protocol defined Inclusion and Exclusion criteria apply

CHAPTERS
Introduction 00:00
Current Treatment Options 00:15
The Need for Better Options 1:51
FLT201 Overview 3:43
Lower Age Limit Criteria 5:17
GALILEO-3 Clinical Trial 5:37
Take Home Message 6:12

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The CheckRare Brief delivers a concise summary of the week's most important developments in rare diseases. Each episode covers FDA approvals, clinical trial updates, conference highlights, scientific publications, and industry news that matter to healthcare professionals, researchers, advocates, and the rare disease community.

Madaline Spencer, Podcast Producer; James Radke, PhD; Education Director; Peter Ciszewski,  Founder and CEO, CheckRare 

 References for this episode’s topics: FDA Advisory Report on Capricor Therapeutics’ Orphan Drug to Treat Cardiomyopathy in Duchenne Muscular DystrophyFDA Advisory Board Report: Link (https://www.fda.gov/advisory-committees/advisory-committee-calendar/cellular-tissue-and-gene-therapies-advisory-committee-july-29-2026-meeting-announcement-updated) Capricor’s response: Link (https://www.capricor.com/investors/news-events/press-releases/detail/351/capricor-therapeutics-provides-update-on-fda-advisory)  Cognitive Decline in Immune ThrombocytopeniaInterview with Dr. David Kuter: Link (https://checkrare.com/going-beyond-lab-values-cognitive-impairment-in-patients-with-immune-thrombocytopenia/)  August is SMA Awareness MonthSMA Awareness Page: Link (https://checkrare.com/august-is-sma-awareness-month/)  The CheckRare Podcast Network is dedicated to delivering news, education, and expert insights across the rare disease community. From physician interviews and conference coverage to weekly news updates and patient stories, our family of podcasts connects healthcare professionals, researchers, advocates, industry leaders, and patients with the information that matters most. Produced by CheckRare, each series is designed to advance awareness, education, and clinical care in rare diseases. For more information, visit www.CheckRare.com (http://www.checkrare.com)

Produced by CheckRare.

Explore additional CME activities, physician interviews, podcasts, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for the latest rare disease education, expert interviews, and weekly news.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

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Ryan Bucco, PharmD, Vice President of Medical Affairs in Rare Disease at Acadia, discusses the LOTUS study in patients with Rett syndrome treated with Daybue (trofinetide).

Rett syndrome is a neurodevelopmental condition that primarily affects girls. People with the disease appear to have normal psychomotor development during the first 6 to 18 months of life, followed by a developmental “plateau,” and then rapid regression in language and motor skills. Additional signs and symptoms may include repetitive, stereotypic hand movements, fits of screaming and inconsolable crying, autistic features, panic-like attacks, teeth grinding, episodic apnea and/or hyperpnea, gait ataxia and apraxia, tremors, seizures, and slowed head growth. Classic Rett syndrome is most commonly caused by genetic changes in the MECP2 gene.

At the 2026 IRSF Rett Syndrome Scientific Meeting, real-world benefits and tolerability of trofinetide for the treatment of patients with atypical rett syndrome in the LOTUS study were presented. LOTUS is an ongoing, caregiver reported, real world, observational phase 4 study designed to better understand how trofinetide is being used and tolerated in routine clinical practice and to capture caregiver reported experiences over time.

Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor-1, approved for treatment of Rett syndrome in 2023. Daybue Stix is an oral, dye- and preservative-free powder formulation of the treatment approved in December 2025 and now available in the US for patients 2 years of age and older. The objective with this new formula was to address concerns related to taste, dosing volume, portability, dietary restrictions, and food sensitivities.

The goal of this study was to describe the real-world effects of trofinetide in individuals with Rett syndrome using the 18-month follow-up analysis of the LOTUS study.

A total of 227 caregivers participated in this analysis. The median trofinetide dose at week 1 was 36% of the target dose and increased to over 80% by week 10 onwards. 55.2% of patients took the full trofinetide recommended daily dose. Caregivers (71%-90%) reported behavioral improvements across months 1 to 12 with the Behavioral Improvement Questionnaire (BIQ), including non-verbal communication (48%-71%), alertness (44%-70%), and social interaction and connectedness (33%-58%). The median Quality of Life Inventory-Disability (QI-Disability) total score change from baseline ranged from 4.7 to 4.6 in months 1 to 12. The incidence of diarrhea varied from weeks 1 to 12 (23%-50%) and months 4 to 12 (26%-38%); most reports of diarrhea were contained inside the patient's diaper. Safety reports were consistent with previous trofinetide clinical trials.

Dr. Bucco also highlights the differences in findings between subgroups including patients with atypical Rett syndrome and male patients with Rett syndrome.

CHAPTERS
Introduction 00:00
LOTUS Study Results 00:39
Subgroup Analysis 2:32
Daybue Stix Effect on Real-World Outcomes 4:59
Take Home Message 6:34

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The CheckRare Brief delivers a concise summary of the week's most important developments in rare diseases. Each episode covers FDA approvals, clinical trial updates, conference highlights, scientific publications, and industry news that matter to healthcare professionals, researchers, advocates, and the rare disease community.

Madaline Spenser; Podcast Editor
James Radke, PhD; Education Director
Peter Ciszewski; Founder and CEO, CheckRare

References for this episode’s topics
FDA Advisory Report on Capricor Therapeutics’ Orphan Drug to Treat Cardiomyopathy in Duchenne Muscular Dystrophy
Link to Advisory Board Report is here https://www.fda.gov/advisory-committees/advisory-committee-calendar/cellular-tissue-and-gene-therapies-advisory-committee-july-29-2026-meeting-announcement-updated
Link to Capricor’s response is here https://www.capricor.com/investors/news-events/press-releases/detail/351/capricor-therapeutics-provides-update-on-fda-advisory

Cognitive Decline in Immune Thrombocytopenia
Link to interview with Dr. David Kuter is here https://checkrare.com/going-beyond-lab-values-cognitive-impairment-in-patients-with-immune-thrombocytopenia/

August is SMA Awareness Month
Link to our SMA Awareness Page is here https://checkrare.com/august-is-sma-awareness-month/

The CheckRare Podcast Network is dedicated to delivering news, education, and expert insights across the rare disease community. From physician interviews and conference coverage to weekly news updates and patient stories, our family of podcasts connects healthcare professionals, researchers, advocates, industry leaders, and patients with the information that matters most. Produced by CheckRare, each series is designed to advance awareness, education, and clinical care in rare diseases.

For more information, visit www.CheckRare.com

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Bruno Fattizzo, MD, Department of Oncology and Hemato-Oncology at the University of Milan, discusses results from the ENERGY clinical trial of Imaavy (nipocalimab) in warm autoimmune hemolytic anemia (wAIHA).

wAIHA is a rare hematologic autoimmune condition characterized by antibodies that attack red blood cells and lead to hemolytic anemia. Symptoms may include unusual weakness and fatigue with tachycardia and breathing difficulties, jaundice, dark urine and/or splenomegaly. The cause of wAIHA is unknown. There are currently no FDA approved therapies indicated for wAIHA.

Results from the phase 2/3 ENERGY clinical trial (NCT04119050) were presented at the European Hematology Association (EHA) 2026 Congress held in Stockholm, Sweden. The ENERGY study was a randomized, double-blind, 24-week evaluating the safety and efficacy of intravenous nipocalimab in patients with wAIHA. Nipocalimab is an immunoselective neonatal Fc receptor (FcRn) blocker designed to reduce circulating IgG levels, including autoantibodies.

A total of 115 participants were randomized to nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, or placebo. At baseline, median time from diagnosis was 2.7, 3.7, and 1.9 years and concomitant corticosteroids were used by 89%, 86% and 87%, respectively.

Durable hemoglobin response was achieved by 24% of patients on nipocalimab 30 mg/kg q4w and 21% on 15 mg/kg q2w versus 8% on placebo. Mean hemoglobin increased by 1.1 g/dL at week 1 on nipocalimab 30 mg/kg q4w and 0.7 g/dL on 15 mg/kg q2w versus -0.1 g/dL on placebo. Hemoglobin level 10 g/dL or more and increase of 2 g/dL or more at 1 or more visits was achieved by 61% on nipocalimab 30 mg/kg q4w and 42% on 15 mg/kg q2w versus 15% on placebo.

FACIT-Fatigue improvement was observed from week 2 to week 24, with mean improvements of 3.4 for nipocalimab 30 mg/kg q4w and 1.2 for 15 mg/kg q2w versus 0.6 for placebo at week 24. The mean reduction in corticosteroid dose at week 24 was 15% for nipocalimab 30 mg/kg q4w and 14% for 15 mg/kg q2w versus 4% (16) for placebo.

Safety findings were consistent with nipocalimab’s known safety profile and wAIHA-associated risks. The proportion of patients with 1 or more adverse events was similar across groups. The most common adverse events included fatigue, diarrhea, asthenia, dizziness, headache, peripheral edema and pyrexia. Grade 3 or greater infections were less frequent with nipocalimab treatment versus placebo. Two deaths, both deemed not related to study drug, occurred in the nipocalimab 15 mg/kg q2w group.

CHAPTERS
Introduction 00:00
Unmet Needs in wAIHA 1:15
ENERGY Clinical Trial Outcomes 3:03
Rapid Hemoglobin Improvements 4:33
Addressing Fatigue 5:38
Take Home Message 6:33

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This program is supported by educational grants from argenx and UCB, Inc.

This accredited CME program highlights the latest clinical research about myasthenia gravis, a rare, autoimmune disease that targets the neuromuscular junction.

To obtain CME credit for this activity, visit https://checkrare.com/learning/p-myasthenia-gravis-clinical-research-highlights-2026/

Management of myasthenia gravis is highly individualized and depends largely on the disease subtype and comorbidities of each patient. Recent clinical studies have expanded the evidence base for approved and emerging therapies, providing clinicians with new information that may inform treatment selection and long-term disease management. Highlights from the American Academy of Neurology Annual Meeting (AAN 2026) include data on approved therapies, their use in specific patient populations, and investigational approaches currently under evaluation.

Led by Drs. Ratna Bhavaraju-Sanka and Chilvana Patel, this program summarizes clinically relevant findings and discusses their potential implications for enhancing the care of patients with myasthenia gravis.

Target Audience
This activity has been designed to meet the educational needs of physicians specializing in neurology, ophthalmology, rheumatology, and family practice. Other members of the care team may also participate.

Learning Objectives
After participating in the activity, learners should be better able to:
Summarize key advances in MG research presented at AAN 2026 and discuss their potential implications for diagnosis, monitoring, and long-term management.

Communicate clinically relevant updates in MG research to members of the multidisciplinary care team to support coordinated, evidence-based patient care.

Ratna Bhavaraju-Sanka, MD, FAAN
Associate Professor,
University of Texas Health, 
San Antonio, TX
Chilvana Patel, MD, FANA
Clinical Associate Professor,
University of Texas Medical Branch, 
Galveston, TX

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. Bhavaraju-Sanka discloses the following relevant financial relationships with ineligible companies:
Consultant: Amgen, argenx

Dr. Patel has no relevant financial relationships with any ineligible companies.

Academy and CheckRare CE planners and reviewers 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 0.50 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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Contact
For any questions, please contact: [email protected]

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