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 ProducerJames Radke, PhD; Education DirectorPeter Ciszewski; Founder and CEO, CheckRare 

 References for this episode’s topicsFDA 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)

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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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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
Gene 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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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.
Privacy
For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare’s privacy policy, please access https://checkrare.com/privacy/

Contact
For any questions, please contact: [email protected]

Copyright
© 2026.
...

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August is SMA Awareness Month, a time dedicated to increasing understanding of spinal muscular atrophy (SMA) and supporting the individuals and families impacted by this rare genetic neuromuscular condition. SMA affects the motor neurons, causing progressive muscle weakness and loss of movement. Most SMA types are caused by mutations in the SMN1 gene, while extra copies of the SMN2 gene modify the severity of disease. Early diagnosis and ongoing specialized care can make a significant difference in patient outcomes.

SMA has undergone a remarkable transformation over the past decade, with advances in disease-modifying therapies fundamentally improving muscle strength, patient mobility, and quality of life in persons living with this condition. However, many patients continue to face disease-related challenges that need to be recognized.

SMA Awareness Month is an opportunity to recognize the importance of continued research, multidisciplinary care, patient advocacy, and education within the rare disease community.

At CheckRare, we are committed to raising awareness of rare disorders like SMA and helping connect healthcare professionals and patients with timely educational resources, expert insights, and emerging clinical developments.

For insights on SMA from the Muscular Dystrophy Association (MDA) 2026 Clinical & Scientific Conference, visit https://checkrare.com/sma-in-focus-practical-insights-from-mda-2026/

To learn more about the development of Itvisma gene therapy for SMA, visit https://checkrare.com/itvisma-gene-therapy-for-patients-with-spinal-muscular-atrophy/

To learn about the changing definition of success in the care and management of SMA, visit https://checkrare.com/spinal-muscular-atrophy-the-changing-definition-of-success/

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Pete Schmidt, MD, MSc, Chief Medical Officer of Portal Therapeutics, discusses data from the phase 2a GATEWAY trial testingPORT-77, an ABCG2 inhibitor, in patients with erythropoietic protoporphyria (EPP).

EPP is a rare congenital metabolic disorder characterized by an inborn error of porphyrin-heme biosynthesis. Signs and symptoms include painful cutaneous photosensitivity leading to blistering and scarring of the exposed skin areas, erythrodontia, red discoloration of urine, hemolytic anemia, and splenomegaly.

The phase 2a GATEWAY clinical trial (NCT06971900) was a blinded, randomized, placebo-controlled crossover trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic effects on plasma protoporphyrin IX (PPIX) of PORT-77 in adults with EPP.

PORT-77 is a novel investigational oral, small molecule ABCG2 inhibitor designed to modify efflux of PPIX from the red blood cell to the plasma and from hepatocytes to the biliary tract.

A total of 19 patients enrolled and received placebo followed by 180 mg of PORT-77 oral suspension once daily (QD) or 300 mg twice daily (BID) for four days.

Results presented at the European Hematology Association (EHA) 2026 Congress highlighted the potential of PORT-77 in causing rapid, dose-dependent reductions in plasma PPIX. A mean decrease of 79% in plasma PPIX was observed in participants receiving 300 mg BID and 63% for those receiving 180 mg QD. These reductions were observed within hours of treatment in both dose groups with no rebound effect after dosing cessation. Additionally, these reduction rates were consistent across a broad range of baseline PPIX levels.

PORT-77 was well tolerated, with no serious adverse events, treatment discontinuations, or tolerability signals observed.

Based on these results, initiation of the global phase 2b/3 PATHWAY trial evaluating the safety and efficacy of PORT-77 in patients with EPP and XLP is expected in Q3 2026.

To learn more about EPP and other rare metabolic conditions, visit https://checkrare.com/diseases/metabolic-disorders/

CHAPTERS
Introduction 00:00
EPP Overview 00:57
Diagnostic Journey 2:44
Signs and Symptoms 4:35
Current Management 5:19
PORT-77 Overview 7:47
GATEWAY Clinical Trial 9:38
Take Home Message 12:46

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Jim Herbert, a patient with ROS1-positive non-small cell lung cancer (NSCLC), discusses his diagnosis and treatment journey.

ROS1-positive NSCLC is a rare and aggressive lung cancer that typically occurs in patients aged 50 years and older and who have never smoked. Brain metastases are common in patients with this condition.

Mr. Herbert, a longtime ice hockey referee and coach, has always been healthy, active, and a lifelong non-smoker. However, in 2024, a cough that returned at the end of every hockey season caused a fractured rib, and scans found a mass in his lung. Additional biomarker testing later identified a highly rare ROS1 mutation, ultimately leading to a diagnosis of advanced ROS1-positive NSCLC.

Chemotherapy and surgery to remove part of his lung was started quickly and after his mutation was confirmed, he began targeted therapy Ibtrozi (taletrectinib), which he remains on today. Starting on this treatment allowed Mr. Herbert to get back on the ice and keep reffing.

His message to other patients is to stay positive and continue to believe, noting the importance of taking good care of yourself throughout treatment and beyond.

To learn more about ROS1-positive NSCLC and other rare cancers, visit https://checkrare.com/diseases/cancers/

CHAPTERS
Introduction 00:00
Diagnostic Journey 00:47
Treatment and Management 2:08
Returning to the Ice 6:16
Message to Other Patients 7:16

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