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Laurie Gutmann, MD, professor of neurology at Indiana University, discusses data showing functional improvements with zeleciment basivarsen (z-basivarsen; DYNE-101) in patients with myotonic dystrophy type 1. Myotonic dystrophy type 1 (DM1), also known as Steinert disease, is a rare, inherited type of muscular dystrophy. Its estimated worldwide prevalence is approximately 1 in 20,000 people. DM1 impacts the muscles and other body systems, including the heart, eyes, endocrine system, and central nervous system.  There are three forms of the disease: mild form, classic form, and congenital form (present at birth). The mild form typically causes the least severe symptoms, and patients generally have a normal lifespan. The classic form causes muscle weakness and wasting, myotonia, cataracts, and, in many cases, abnormal heart function. Adults with the classic form may become physically disabled and have a shortened lifespan. The congenital form is characterized by severe generalized weakness at birth, often accompanied by breathing complications that can be life-threatening. DM1 is caused by an abnormal expansion of repeated DNA sequences in the DMPK gene. Zeleciment basivarsen is an investigational therapy consisting of an antisense oligonucleotide (ASO) conjugated to an antigen-binding fragment (Fab) that binds to the transferrin receptor 1 (TfR1) to enable delivery to muscle and the central nervous system. It’s designed to improve function in individuals living with DM1 by reducing toxic DMPK RNA, releasing splicing proteins, and allowing normal mRNA processing. Z-basivarsen has been granted Breakthrough Therapy, Orphan Drug, and Fast Track designations by the U.S. Food and Drug Administration (FDA) Additional one-year efficacy data from the multiple ascending dose (MAD) portion of the phase 1/2 ACHIEVE trial (NCT05481879) were announced on September 29, 2026, and presented at the 2026 World Muscle Society Congress and the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting. ACHIEVE is a randomized, placebo-controlled, double-blind, phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of z-basivarsen in patients with DM1. The pooled analysis included 25 to 26 participants from three dose groups: 3.4 mg/kg every four weeks, 5.4 mg/kg every eight weeks, and 6.8 mg/kg every eight weeks. Some participants initially received a placebo before switching to active treatment. Only 8 of the 26 participants received the selected 6.8/kg dose for the full 12 months. The pooled data showed improvements in several areas, including: Hand myotonia: At six months, video hand opening time improved by 3.2 seconds from baseline in the pooled treatment group, compared with a 0.4-second increase in the placebo group. Physical function: At 12 months, participants improved their five-times sit-to-stand test by 1.2 seconds and their 10-meter walk/run test by 0.3 seconds relative to baseline. Muscle strength: Quantitative muscle testing showed improvements in both the total score and hand grip, with each increasing by 4.8% relative to baseline. Patient-reported outcomes: The Myotonic Dystrophy Health Index total score improved by 25.2% relative to baseline.No treatment-related serious adverse events were identified. The ACHIEVE trial's registrational expansion cohort is fully enrolled, with topline results expected in the first quarter of 2027. The study's primary endpoint is the change in video hand opening time after six months of treatment. Dyne Therapeutics plans to use these results to support a potential U.S. accelerated approval submission in the third quarter of 2027.Dyne Therapeutics is also conducting the phase 3 HARMONIA trial to further evaluate z-basivarsen. The HARMONIA trial is intended to confirm the treatment's benefits and support a potential application for traditional FDA approval. For more information, visit: https://www.globenewswire.com/news-release/2026/09/29/3371326/0/en/dyne-therapeutics-announces-additional-one-year-clinical-data-from-phase-1-2-achieve-trial-of-z-basivarsen-dyne-101-for-myotonic-dystrophy-type-1-dm1.html To learn more about myotonic dystrophy type 1 and other rare neurological and neuromuscular disorders, visit: https://checkrare.com/diseases/neurology-nervous-system-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Andrea Callaway, president and founder of The Nephrotic Syndrome Foundation, discusses the FDA approval of Gazyva (obinutuzumab) for idiopathic nephrotic syndrome (INS) and what the approval means for affected families.  INS is a rare autoimmune kidney disease that’s commonly diagnosed in early childhood. It causes the kidneys to leak large amounts of protein into the urine, which can result in weight gain, swelling, and fatigue. Patients may also experience an increased risk of complications, such as infections and blood clots.  Steroids have traditionally been used to treat patients with INS, but between 60% and 90% of patients experience relapse. Furthermore, steroid-related side effects can make long-term treatment challenging. On September 25, 2026, obinutuzumab received FDA approval to reduce the risk of relapse in adults and children ages two years and older with frequently relapsing or steroid-dependent childhood-onset INS who are in complete remission. It’s the first treatment approved for INS in more than 70 years. Obinutuzumab is a monoclonal antibody that targets B cells involved in immune activity. It’s designed to help INS patients maintain remission and lower the risk of relapses.  Results from the INShore clinical trial (NCT05627557) were announced by Roche on October 28, 2025. The INShore study was a phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of obinutuzumab compared to mycophenolate mofetil (MMF) in patients with childhood-onset INS. The study found that 95% of participants receiving  obinutuzumab experienced no relapses after week 8 and were in complete remission by week 52, compared with 73% of participants receiving MMF.  Secondary endpoints included statistically significant and clinically meaningful benefits in overall relapse-free survival, median time to first relapse or death, and the number of relapses through week 52, all compared with MMF.  No new safety signals were observed with obinutuzumab. For more information, visit: https://www.gene.com/media/statements/ps_092526 To learn more about idiopathic nephrotic syndrome and other rare kidney and urinary diseases, visit: https://checkrare.com/diseases/kidney-and-urinary-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Andrew Dauber, MD, MMsc, Chief of Endocrinology at Children’s National, discusses the efficacy of vosoritide to treat persons with hypochondroplasia. Hypochondroplasia is a rare skeletal disease characterized by very short stature, similar to achondroplasia, but with milder features. People with hypochondroplasia usually have very short stature, large head, accentuated lordosis, short arms and legs, and broad, short hands and feet. Other features include a limited range of motion in the elbows, lordosis, and bowed legs. Uncommon symptoms may include learning difficulties and convulsions. Hypochondroplasia is often caused by genetic changes in the FGFR3 gene. Vosoritide is a C-type natriuretic peptide analogue being investigated for the treatment of hypochondroplasia. It is currently approved for the treatment of achondroplasia. In the phase 3, multicenter CANOPY-HCH-3 (NCT06455059) clinical trial, children with hypochondroplasia who were 3 to less than 18 years of age were randomly assigned to receive once-daily subcutaneous injections of vosoritide or placebo for 52 weeks per weight-band dosing regimen.  A total of 81 participants were randomly assigned to receive vosoritide or placebo. At week 52, the least squares mean (LSM) change from baseline in annualized growth velocity was 1.95 cm/year with vosoritide versus −0.39 cm/year with placebo. Dr. Dauber also explains that patients in the vosoritide group also showed an increase in arm span of more than a centimeter compared to the placebo group. 87.8% of participants in the vosoritide group and 72.5% of the placebo group experienced at least one adverse event. There were no reports of grade 3 or higher adverse events, adverse events leading to treatment discontinuation, or deaths. For more information, visit The New England Journal of Medicine Evidence. To learn more about hypochondroplasia and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Daniela Rogoff, MD, PhD, Chief Medical Officer, Skeletal Dysplasia of BridgeBio, discusses the efficacy of infigratinib to treat persons with achondroplasia. Achondroplasia is a disorder of bone growth that prevents the changing of cartilage to bone, particularly in the long bones. It is characterized by dwarfism, limited range of motion at the elbows, macrocephaly, and small fingers. Achondroplasia can cause health complications such as apnea, obesity, recurrent ear infections, and lordosis. More serious problems include spinal stenosis and hydrocephalus. Some patients may have delayed motor development early on, but cognition is normal. Achondroplasia is caused by genetic changes in the FGFR3 gene. Positive topline results from the PROPEL 3 clinical trial (NCT06164951) of oral infigratinib in children living with achondroplasia were recently announced. PROPEL 3 was a phase 3, global, one-year, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of infigratinib in children with achondroplasia, ages 3 to 18 years, with open growth plates.  Infigratinib is a selective, reversible, ATP-competitive tyrosine kinase inhibitor primarily targeting the fibroblast growth factor receptors FGFR1, FGFR2, and FGFR3. Key results from the study through week 52 included a change from baseline in annualized height velocity (AHV) superior to placebo, with an LS mean treatment difference of +1.74 cm/year and a mean treatment difference of +2.10 cm/year. Absolute AHV at week 52 also showed a significant improvement with infigratinib compared to placebo. Change from baseline in height Z-score was superior to placebo, with an LS mean treatment difference of +0.32 standard deviations (SD) and the LS mean change from baseline on the treatment arm of +0.41 SD. In an exploratory analysis of children younger than 8, oral infigratinib showed statistical significance against placebo in change from baseline in upper-to-lower body proportionality at week 52, demonstrating an LS mean decrease of -0.05 against placebo. In the overall population, infigratinib achieved an LS mean decrease of -0.05, with a favorable LS treatment difference of -0.02 versus placebo at week 52. Infigratinib was well-tolerated, with no discontinuations and no serious adverse events related to the study drug. Based on these results, plans for submission of a New Drug Application (NDA) and Marketing Authorization Application (MAA) for infigratinib are underway. BridgeBio is currently enrolling participants in the observational run-in for the phase 3 trial and has an ongoing clinical trial of infigratinib for the newborn to 3 year old age groups in achondroplasia in the PROPEL Infant & Toddler trial (NCT07169279). For more information, visit https://www.globenewswire.com/news-release/2026/09/09/3358343/0/en/oral-infigratinib-shows-meaningful-benefits-beyond-growth-within-52-weeks-in-children-with-achondroplasia-in-the-phase-3-propel-3-trial.html To learn more about achondroplasia and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Jane Salmon, MD, Professor of Medicine at Weill Cornell Medical College, discusses antiphospholipid syndrome (APS), its impact on pregnancy, and emerging research into Cimzia (certolizumab pegol) as a potential approach to preventing serious pregnancy complications.  APS is an autoimmune condition characterized by an increased risk of thrombosis and serious pregnancy complications (e.g., preeclampsia, placental insufficiency, growth restriction, intrauterine fetal death, and recurrent early miscarriages). Thrombosis may also cause severe, life-threatening complications such as stroke. Diagnosis involves testing for three types of antibodies: anti-cardiolipin, anti-beta 2 GP1, and the lupus anticoagulant, with the latter carrying the highest risk for thrombosis and pregnancy complications. Despite the significant burden of the condition, there are currently no FDA-approved therapies and patients are typically managed with low-dose aspirin and heparin. The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to certolizumab pegol for the prevention of placenta-mediated adverse pregnancy outcomes in pregnant women who have APS and are positive for lupus anticoagulant. Certolizumab pegol is a tumor necrosis factor (TNF) blocker currently indicated for a variety of autoimmune conditions. Breakthrough Therapy Designation is granted to treatments intended to address serious or life-threatening conditions when preliminary clinical evidence indicates the therapy may demonstrate substantial improvement over available treatments on one or more clinically significant endpoints. The designation is designed to facilitate development and expedite the FDA review of promising new therapies. The designation for certolizumab pegol is supported by preliminary clinical evidence from the IMPACT clinical trial (NCT03152058). The trial met its primary endpoint, reducing the adverse outcome rate to 20% in the study population, compared to a 44% historical adverse outcome rate. Furthermore, 95% of the women in the trial had live-born babies who survived to hospital discharge, marking a significant improvement over the 37% rate observed in the participants' previous pregnancies. Although the intervention did not completely eliminate adverse outcomes, it made them significantly less severe by allowing for later gestational ages at the time of delivery. For more information, visit https://www.prnewswire.com/news-releases/ucb-receives-us-fda-breakthrough-therapy-designation-for-cimziacertolizumab-pegol-in-pregnant-women-with-antiphospholipid-syndrome-aps-302873706.html To learn more about rare autoimmune conditions, visit https://checkrare.com/diseases/autoimmune-autoinflammatory-disorders/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Keisha L. Gibson, MD, MPH, pediatric nephrologist at the UNC School of Medicine, discusses the approval of Gazyva (obinutuzumab) for patients with childhood-onset idiopathic nephrotic syndrome (INS). INS is a rare, autoimmune kidney disease that is often managed by corticosteroids and/or mycophenolate mofetil. The disease and treatment however, is characterized by unpredictable relapses that cause fatigue, swelling, weight gain and increased susceptibility to infections and clotting. These flare-ups or relapses also lead to anxiety, depression and reduced self-esteem, brought on by the fear of relapse and social isolation. It is usually diagnosed in early childhood and is the most common form of primary glomerular disease in children. Obinutuzumab is a humanized type II anti-CD20 monoclonal antibody that binds to the CD20 antigen, a proven target for CD20+ B cells. It is the first treatment option for INS to be approved in 70 years. It is currently indicated to reduce the risk of relapse in adult and pediatric patients 2 years of age and older with frequently relapsing or steroid dependent childhood-onset INS who are in complete remission. The approval is based on results from the phase 3 INShore clinical trial (NCT05627557). More obinutuzumab-treated patients experienced no relapses after week 8 and were in complete remission at one year (95%) compared with mycophenolate mofetil (MMF) (73%). Analysis of key secondary endpoints showed statistically significant and clinically meaningful benefits with obinutuzumab with an increase in those with overall relapse-free survival, median time to first relapse or death, and fewer relapses from baseline to week 52, all compared with MMF. Additionally, no new safety signals were observed. This approval is significant to patients and families living with INS because it provides an alternative treatment option to daily oral medications and the toxicities associated with chronic steroid use. For more information on this approval, visit https://www.gene.com/media/statements/ps_092526 or https://checkrare.com/fda-approves-gazyva-obinutuzumab-for-treatment-of-childhood-onset-idiopathic-nephrotic-syndrome/ To learn more about INS and other rare kidney conditions, visit https://checkrare.com/diseases/kidney-and-urinary-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Kyle Loh, PhD, Associate Professor at Stanford Medicine, discusses research that could help scientists better understand spinal muscular atrophy (SMA) by generating new motor neurons from human hindbrain cells in the laboratory.     SMA is a genetic neuromuscular disorder characterized by the loss of motor neurons, causing progressive muscle weakness and loss of movement due to atrophy. SMA mainly affects the muscles involved in walking, sitting, arm movement, and head control. Breathing and swallowing may also become difficult as the disease progresses. SMA is caused by genetic mutations in the SMN1 gene. Extra copies of the nearby related gene, SMN2, modify the severity of SMA, with type 1 being the most severe and type 4 the least severe.  The study by Dr. Loh and his colleagues examined how different parts of the brain develop and use that knowledge to create new ways to generate new cells, including motor neurons. While the brain is often viewed as a single organ originating from one source, it is actually built from two distinct sources: one creating the forebrain/midbrain and another creating the hindbrain. As Dr. Loh explains, this distinction is critical for understanding the evolution of the brain and for developing human neurons in a laboratory setting. Neurons in the hindbrain have received less attention than the well-studied spinal cord motor neurons. However, these hindbrain neurons are essential for life-sustaining functions, including eating, swallowing, speech, and facial movements. To study these neurons, specific genes that mark different progenitor cells were identified: OTX2 for forebrain/midbrain and GBX2 for the hindbrain. By directing stem cells toward these specific progenitor states, hindbrain motor neurons can be generated in a petri dish. This study includes the creation of human induced pluripotent stem cell lines from patients with type 1 SMA to observe how the condition affects the growth of hindbrain motor neurons. Dr. Loh is also interested in exploring the pathophysiology of SMA further. For example, the SMN1 gene is ubiquitously expressed in every cell in the body, its loss specifically impacts a small subset of motor neurons in patients with SMA. Further work is also needed to investigate why certain motor neurons, such as those innervating the diaphragm, appear resilient in  patients with SMA while muscles nearby are impacted. Understanding this natural resilience could offer a new approach to therapy that moves beyond simply replacing the missing gene. For more information, visit https://www.nature.com/articles/s41593-026-02433-7 To learn more about SMA and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

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. 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.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.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.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.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 regionIf 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] 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 To learn more about AML and other rare cancers, visit https://checkrare.com/diseases/cancers/ 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. Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Jorge Nieva, MD, Associate Professor at the Keck School of Medicine, discusses new analyses from the TRUST studies evaluating taletrectinib in patients with ROS1-positive non-small cell lung cancer (NSCLC). ROS1-positive NSCLC is a rare molecular subtype of non-small cell lung cancer in which changes involving the ROS1 gene can drive tumor growth. Identifying ROS1-positive disease is important because these patients may benefit from targeted therapies designed to inhibit ROS1 signaling. Taletrectinib is a next-generation ROS1 tyrosine kinase inhibitor being evaluated for the treatment of patients with advanced ROS1-positive NSCLC. At the 2026 World Conference on Lung Cancer, investigators presented new analyses from the TRUST studies examining the efficacy of taletrectinib across key patient subgroups. The analyses demonstrated consistent efficacy across the evaluated subgroups, with responses showing durability in patients with advanced ROS1-positive NSCLC. These findings provide additional insight into the potential clinical benefit of taletrectinib across a range of patient characteristics and treatment histories. Dr. Nieva discusses the TRUST study findings and explains the importance of evaluating both the magnitude and durability of response when considering treatment options for patients with ROS1-positive NSCLC. The safety profile of taletrectinib was also evaluated in the TRUST studies. Dr. Nieva reviews the most commonly reported adverse events and discusses considerations for managing treatment-related toxicities in clinical practice. As targeted therapies continue to evolve for patients with ROS1-positive NSCLC, the TRUST findings provide additional information about the efficacy and safety of taletrectinib and its potential role in the treatment of this rare form of lung cancer. To learn more about NSCLC and other rare lung conditions, visit https://checkrare.com/diseases/lung-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Michael Benatar, MD, PhD, Department of Neurology and ALS Center, University of Miami Miller School of Medicine, discusses the use of plasma proteomics in predicting clinical manifestations of amyotrophic lateral sclerosis (ALS). ALS is a rare motor neuron disease characterized by problems with muscle control and movement. Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or difficulty chewing or swallowing. There are various types of ALS depending on symptoms, and sometimes, genetic cause. Most people with ALS have a sporadic form of ALS. It is believed that these cases are caused by an interaction between genetic and environmental factors. Familial ALS may be caused by genetic changes in any one of several genes and the pattern of inheritance varies depending on the gene involved. A study published in Nature Medicine looked at longitudinal plasma proteomics to predict phenoconversion to clinically manifest ALS. The study was conducted in patients with pre-symptomatic ALS to predict which unaffected carriers of ALS-associated pathogenic variants will phenoconvert to clinically manifest disease and when, with the hopes of designing more effective disease prevention trials. A total of 516 serially collected plasma samples from 33 phenoconverters, 35 patients with ALS, 10 pre-symptomatic pathogenic variant carriers, and 59 controls were included. 92 proteins were then identified with concentrations that changed before phenoconversion and the longitudinal trajectory of these proteins was characterized. A core panel of 19 proteins was identified which, collectively, predicted phenoconversion over the 0.5-year to 5-year time horizons and resulted in estimates of time to phenoconversion with a mean absolute error of 1.6 years. These findings were partially replicated in UK Biobank data, confirming pre-symptomatic increases in several proteins (including NEFL, EDA2R and CA3) and that a multi-protein panel outperformed NEFL alone in estimating time to phenoconversion. To learn more about ALS and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Lukasz Jarzyna, Vice President of Rare Disease at LEO Pharma, discusses the Priority Review for dersimelagon in the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP). EPP and XLP are rare congenital metabolic disorders characterized by an inborn error of porphyrin-heme biosynthesis. Signs and symptoms include painful cutaneous photosensitivity that results in tingling, burning, pain, and itching within minutes of sun/light exposure and may be accompanied by swelling and redness. Other symptoms may include erythrodontia, red discoloration of urine, hemolytic anemia, and splenomegaly. On September 18, the US Food and Drug Administration (FDA) announced Priority Review to the New Drug Application (NDA) for dersimelagon for the treatment of EPP and XLP, with a PDUFA date of February 2027. Dersimelagon is an investigational, once-daily oral small-molecule MC1R agonist being developed for EPP and XLP. Under a Priority Review designation, the FDA aims to take action on an application within 6 months, compared to 10 months under standard review. LEO Pharma also announced an acquisition of worldwide rights to dersimelagon from Tanabe Pharma. Earlier this year, Tanabe Pharma announced results from the global, randomized, double-blind, placebo-controlled phase 3 INSPIRE clinical trial (NCT06144840). Dersimelagon demonstrated statistically significant and clinically meaningful outcomes across primary and secondary endpoints, including a significant prolongation of average daily sunlight exposure time to first prodromal symptoms. If approved, dersimelagon could become the first oral treatment for EPP and XLP. Dersimelagon has not yet been approved by the FDA or any other regulatory authority, and its safety and efficacy have not been established by any regulatory authority. For more information, visit https://leo-pharma.com/media-center/news/leo-pharma-announces-fda-acceptance-of-dersimelagon-nda-with-priority-review-and-closes-acquisition-from-tanabe-pharma/ To learn more about EPP and XLP and other rare skin conditions, visit https://checkrare.com/diseases/skin-conditions/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Nona Baker, Co-Chair of MPN Voice and patient, discusses her journey with essential thrombocythemia (ET) and polycythemia vera (PV), including diagnosis and treatment. ET is a condition characterized by an overproduction of platelets. Abnormal blood clotting is common in these patients and may cause strokes or temporary stroke-like episodes, leg pain, swelling, pulmonary embolism, chest pain and difficulty breathing. A paradoxical problem in ET is abnormal bleeding, such as excessive nosebleeds, bleeding gums, or bleeding in the gastrointestinal tract. Other signs and symptoms include splenomegaly, weakness, headaches, or a sensation in the skin of burning, tingling, or prickling. Some people with ET have episodes of severe pain, redness, and swelling, which commonly occur in the hands and feet. PV is a condition characterized by an increased production of red blood cells. Affected people may also have excess white blood cells and platelets. The excess cell levels lead to thicker blood and increased risk for serious thrombotic events and stroke. PV occurs more frequently in men than it does in women. The condition has been associated with genetic changes in the JAK2 and TET2 genes. Both conditions are considered myeloproliferative neoplasms (MPNs). Ms. Baker’s symptoms first presented as painful feet/legs and extreme fatigue. After bouncing a few doctors who gave her orthopedic insoles and believed she had an alcohol problem, a retest of her bloodwork led to a hematology referral. She was finally diagnosed with essential thrombocythemia (ET) in 1991 and polycythemia vera (PV) in 2004, a time where information on these disorders was scarce. At the time, she was told she had 15 years to live. She notes that her story is similar to a lot of other patients. After diagnosis, Ms. Baker was first treated with a chemotherapy pill and regular venesections. Now, she goes every 8-9 weeks for monitoring and receives treatment whenever her levels become unstable. However, side effects from the medications have caused skin problems, including actinic keratosis and, more recently, basal-cell carcinomas. This highlights the need for further research and treatment options for patients with ET and PV. Ms. Baker stresses that education is key. The more people are aware of MPNs, and know what signs to look for, the faster patients can be referred to hematologists and receive an earlier diagnosis. MPN Voice works to increase education through their mission to provide clear and accurate information and emotional support to everyone who has been diagnosed with an MPN and their families/friends. The organization’s “Buddy Programme” connects newly diagnosed patients with those who have already gone through the challenges of diagnosis and beginning treatment. To learn more about MPNs and other rare hematologic disorders, visit https://checkrare.com/diseases/hematologic-disorders/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Paz Vellanki, MD, PhD, Vice President of Clinical Development at Precision for Medicine, discusses the FDA CDER’s Accelerating Rare Disease Cures (ARC) Program. The ARC Program was launched in 2022 with the goal of accelerating the development of safe and effective therapies for patients with high unmet need with rare diseases. The program has included a variety of initiatives, including several successful pilot programs, patient listening sessions, novel clinical trial design workshops, and a focus on patient-centric drug developments.  Dr. Vellanki explains that drug development for rare diseases is often more complex than common diseases, requiring a different approach from conventional trial designs, including the use of novel endpoints and biomarkers. To address these needs, the ARC Program’s initiatives encourage increased engagement between sponsors and the FDA to enhance formal meetings, an aspect that Dr. Vellanki says is important for small biotech companies who face challenges like small patient populations and complex endpoint selection. Recently, CDER issued a five-year strategic map for the ARC Program, defining what the program was and what stage it is currently in. It analyzes the pilot programs and metrics on success, determining next steps and how to continue efforts across the FDA. Proposed advances focus on strategies to advance scientific and regulatory innovations, expand novel trial tools, and streamline approval pathways for rare disease therapies. Dr. Vellanki notes that many of the ongoing initiatives are focused in specific disease areas, but there is hope for expansion across rare disease categories. To learn more about rare disease drug development, visit https://checkrare.com/drug-development/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Amy Waldman, MD, pediatric neurologist and Medical Director of the Leukodystrophy Center at the Children’s Hospital of Philadelphia, discusses the approval of Zanvastro (zilganersen) to treat patients with Alexander disease. Alexander disease is a rare leukodystrophy that impairs neuronal signalling. Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size, seizures, stiffness in the arms and/or legs, intellectual disability, and developmental delay. Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the central nervous system. Zilganersen is an antisense oligonucleotide that binds to RNA and is designed to inhibit production of excess glial fibrillary acidic protein (GFAP) that accumulates as a result of pathogenic variants in the GFAP gene. It is the first and only disease modifying therapy approved for this indication.  The approval is based on positive results from a global, multicenter, randomized, double-blind, controlled, multiple-ascending dose (MAD) phase 1-3 study (NCT04849741) that enrolled 54 participants with Alexander disease.  The study met its primary endpoint in individuals 5 years of age and older, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT) compared to control at week 61. The treatment also demonstrated a favorable safety and tolerability profile, with most adverse events being mild or moderate in severity. Alexander disease faces a unique challenge to getting on newborn screening panels. Although the disease does typically present in young children, GFAP accumulation may not be high enough to detect at birth. Dr. Waldman explains that research is still being done to determine when the earliest possible diagnosis can be made. However, she highlights the following red flag symptoms that may point to central nervous system involvement and may warrant genetic testing: in younger children these include gross motor and developmental delays, seizures, and in older children, these include more mild symptoms such as hypernasal speech, speech delay, vomiting, and gait imbalance. For more information on the approval, visit https://ir.ionis.com/news-releases/news-release-details/zanvastrotm-zilganersen-approved-fda-first-and-only-disease To learn more about Alexander disease and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

Jenny McCue, Vice President of Global Research and Clinical Development at the Myasthenia Gravis Foundation of America (MGFA), discusses research highlights to be presented at the upcoming 2026 MGFA Scientific Session being held September 29th in Orlando, FL.  Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. It mostly develops in adults but children can also develop this rare condition. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles usually due to the presence of antibodies against the acetylcholine receptor at the neuromuscular junction. The exact reason this occurs is not known. MGFA is a patient advocacy organization focused on driving research through funding and connecting scientists and physicians working on MG around the world. The MGFA works in funding pilot grants for early phase research, as well as foundation and fellowship grants that fund clinical and translational research. This year the organization is launching three new series of grants focused on seronegative, biomarkers, and pediatrics. Visit the MGFA website for more information on grant funding. The MGFA Scientific Session brings together researchers, physicians, and investigators to discuss the newest science in myasthenia gravis. The MGFA Scientific Session will take place Tuesday, September 29, 2026 during the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting. This year’s session will host the most research seen at the event yet, which Ms. McCue says speaks to the growing number of the MG community as well as study areas within the disease. The session is organized around some of these areas that cover the full timeline of the MG journey. Keynote speaker Dr. Sarah Hoffmann will start the day, then the first section of presentations will focus on biomarkers, basic science, and diagnostics. The story then transitions to the second and largest area of research, therapeutics and clinical trials. The third section will focus on seronegative MG. Then, the meeting closes out with “hot topics” of patient care, outcomes, digital health and real world evidence. Complementing the day, poster sessions will run throughout the event. Ms. McCue highlights the importance of healthcare practitioners staying up to date with the latest research. Key areas of focus include the need to be aware of early and more accurate diagnosis, treatment that matches a more individual experience with MG, and better monitoring and access to tools. To learn more about MG and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/ Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.