Richard J. Auchus, MD, PhD, Professor of Internal Medicine and Pharmacology at the University of Michigan Medical School, discusses two-year results of Crenessity (crinecerfont) in the treatment of congenital adrenal hyperplasia (CAH).

CAH refers to a group of genetic conditions that affect the adrenal glands. Affected people lack an enzyme the adrenal glands need to make one or more of these hormones and often overproduce androgens. For example, females with a severe form of the condition may have ambiguous genitalia at birth and if not properly diagnosed, develop dehydration, poor feeding, diarrhea, vomiting and other health problems soon after. People with milder forms may not be diagnosed with the condition until adolescence or adulthood when they experience early signs of puberty or fertility problems.

At the 2026 American Association of Clinical Endocrinology (AACE) Annual Meeting, two-year data from the phase 3 CAHtalyst adult clinical trial of crinecerfont was presented. Crinecerfont is a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist designed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism.

The phase 3 CAHtalyst global registrational studies were designed to evaluate the safety, efficacy and tolerability of crinecerfont in children and adults with classic CAH due to 21-hydroxylase deficiency. The CAHtalyst Adult study included 182 adult patients ages 18 to 58 years. The study evaluated improvement of androgen control over four weeks of crinecerfont treatment and the enabling of GC reduction to physiologic range while androstenedione levels were maintained or improved over an additional 20 weeks of treatment.

At month 24 of the study, 69% (n=149) of participants achieved a physiologic GC dose, with many participants eliminating nonphysiologic GC types. Of participants originally taking dexamethasone (n=20), 75% switched to a dexamethasone-free regimen, while 62% (37/60) of patients taking more than two doses of hydrocortisone per day were able to eliminate a dose outright. GC dose reductions and regimen changes were achieved without worsening androstenedione levels relative to baseline, indicating that lowering the GC dose was not achieved at the expense of androgen control.

Long‑term treatment with crinecerfont was generally well tolerated, with more than 80% study retention at two years and no new safety signals observed.

Data from the CAHtalyst phase 3 studies supported approval of crinecerfont by the US Food and Drug Administration in December 2024. The open-label extension treatment portions of both studies are ongoing.  

Chronic exposure to supraphysiologic GC doses is associated with numerous long-term health risks, including cardiometabolic, bone health and quality-of-life complications. Reducing high-dose, long-term GC exposure represents one of the most important goals in the management of classic congenital adrenal hyperplasia (CAH).

To learn more about CAH and other rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/

CHAPTERS
Introduction 00:00
CAH Overview 00:13
Diagnosis and Current Management 1:50
Two-Year Results 3:10
Weight and Metabolic Outcomes 4:58

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Kinga Tomczak, MD, PhD, Program Director of the Tic Disorders and Tourette Syndrome Program at Boston Children’s Hospital and Assistant Professor of Neurology at Harvard Medical School, discusses phase 3 clinical trial results of ecopipam as a treatment for Tourette syndrome.

Tourette syndrome is a chronic childhood-onset neurodevelopmental disorder characterised by motor and phonic tics that can substantially diminish the quality of life of affected individuals. The underlying pathophysiology of Tourette syndrome is not fully understood, but recent research has brought new insights into the genetic variations and the alterations in neurophysiology and brain networks contributing to its pathogenesis. Tourette syndrome occurs more frequently in males, and males tend to have more severe symptoms than females. Tourette syndrome is often accompanied by comorbid behavioural disorders, including most prominently obsessive-compulsive behaviour and attention deficit disorders.

At the American Academy of Neurology 2026 Annual Meeting (AAN 2026), data was presented from a phase 3 study on the safety and efficacy of ecopipam for the treatment of Tourette syndrome. Ecopipam is a selective dopamine D1 receptor antagonist being investigated as a maintenance therapy in persons with Tourette syndrome.

In the study, patients ages 6 years and older with Tourette syndrome were included in a double-blind, placebo-controlled, randomized withdrawal trial. Ecopipam was titrated over 3 to 4 weeks with a target dose of 1.8 mg/kg/day in the 12 week open-label period. Patients with a clinically meaningful reduction of 25% or greater in Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) at weeks 8 and 12 were randomized to continue ecopipam or taper to placebo in the 12 week double-blind period.

A total of 216 patients were enrolled in the 12 week open-label phase. Overall, 104 patients (90 pediatric) were randomized to the 12 week double-blind period to continue ecopipam or switch to placebo. The risk of relapse was significantly reduced in the ecopipam group compared with placebo in the pediatric and pediatric plus adult populations. The most commonly reported adverse events in the ecopipam group during the 24 week study were somnolence, anxiety, headache, insomnia, tic, and fatigue.

Overall, this study demonstrated ecopipam’s ability to maintain clinically meaningful improvements in Tourette syndrome symptoms. It was generally well-tolerated, with adverse events primarily affecting the central nervous syndrome and did not cause weight gain, dyslipidemia, or drug-induced movement disorders.

To read the abstract presented at AAN 2026, visit https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-004157.html

To learn more about rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
Tourette Syndrome Overview 00:21
Developing Treatments 3:46
Ecopipam Clinical Trial Data 5:23
Clinical Trial Design 11:12
Take Home Message 13:28

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Naji Gehchan, MD, MBA, Chief Medical and Development Officer at Kyverna Therapeutics, discusses new follow-up data on KYV-101 treatment for patients with myasthenia gravis (MG).

Generalized MG (gMG) is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

An update of KYSA-6 (NCT06193889) a phase 2, open-label, single-arm, multicenter study of KYV-101 in gMG was presented at the 2026 American Academy of Neurology Annual Meeting. KYV-101 is a fully human, autologous CD19 CAR T-cell therapy with CD28 costimulation, designed to achieve deep B-cell depletion and immune reset to deliver durable, drug-free, disease-free remission.

In the study, adults ages 18 to 75 years with gMG (MGFA class IIb-IV), history of AChR or MuSK autoantibodies, MG Activities of Daily Living (MG-ADL) score of 6 or greater, and 2 or more immunosuppressant/immunomodulator failures, received lymphodepletion and a single infusion of 1×10^8 CAR T cells.

As of October 2025, 6 patients were dosed and follow-up ranged from 28 days to 9 months. Robust CAR T-cell expansion and B-cell depletion occurred in all patients. With a single dose, 100% of patients had 3-point or greater improvements in MG-ADL from baseline, with 50% achieving minimal symptom expression at last follow-up. At 24 weeks, KYV-101 treatment resulted in 8.0-point and 7.7-point mean reductions from baseline in MG-ADL and QMG scores, respectively. Of the 6 patients, 5 became nonsteroidal immunosuppressant therapy-free. No ICANS and no high-grade CRS events occurred.

Overall, treatment with KYV-101 resulted in robust and sustained improvements in disease severity with an acceptable safety profile, while eliminating background immunosuppressants in the majority of patients. A phase 3 clinical study is ongoing.

To learn more about gMG and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
KYV-101 in Myasthenia Gravis 00:10
Next Steps 1:28

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William W. Motley, MD, RAP-219 Program Leader at Rapport Therapeutics, discusses follow-up data of RAP-219 for the treatment of focal onset seizures.

Focal onset seizures refer to abnormal neural activity in one brain area within one brain hemisphere with a fixed focal or localized onset. These seizures can manifest in various ways, with symptoms ranging from subtle sensory disturbances to more pronounced motor movements and altered consciousness. Focal onset seizures are divided into 2 subtypes: motor onset and nonmotor onset. The motor manifestations of focal motor onset seizures can be characterized as automatism, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, or tonic movements. The behavioral manifestations of focal nonmotor onset seizures can be described by autonomic, behavioral arrest, cognitive, emotional, or sensory symptoms.

At the 2026 American Academy of Neurology (AAN) Annual Meeting, results from the phase 2a trial of RAP-219 in patients with drug-resistant focal onset seizures (FOS) and an implanted responsive neurostimulator (RNS) system were presented. This included data from an 8 week follow-up period.

RAP-219 is a potential first-in-class, TARPγ8-specific AMPA receptor negative allosteric modulator. It is designed to target the TARPγ8 protein that is expressed in brain regions where focal seizures often originate. Because of this protein’s minimal expression in the hindbrain, it is hypothesized that the drug will avoid causing intolerable adverse events often associated with traditional neuroscience medications.

Patients with drug-resistant focal onset seizures, an RNS system, 16 or more long episodes, and 1 or more clinical seizure during an 8 week retrospective period were entered into a prospective baseline followed by an 8 week treatment period. Enrolled patients received RAP-219 0.75 mg/d (5d), then RAP-219 1.25 mg/d for the remainder of the treatment period, followed by an 8-week washout period. Patients had a median 8.5 CSs/28d at baseline. Patients had the RNS implanted a median 4.6 years before first RAP-219 dose and had a baseline median 48 LEs/28d with median 92% concordance between LEs and electrographic seizures.

As previously reported, primary endpoints were achieved with statistical significance. This included a 71% median reduction in long episodes with 85.2% of patients achieving at least a 30% reduction over the 8 week treatment period. Clinical seizures also showed a median 77.8% reduction with 72% of patients achieving a reduction of at least 50% over the treatment period. Additionally, 24% of patients achieved seizure freedom for the entire 8 week treatment period. The most common treatment-emergent adverse events in the safety population included dizziness, headache, fatigue, and falls.

Based on recent data and population PK modeling from the 8 week follow-up period, RAP-219 has demonstrated an approximately 22 day half life. An 80% reduction in median long episodes relative to baseline during the first four weeks of follow-up was observed, compared to 75% for the first four weeks of the initial treatment period. Follow-up also illustrated a 90% reduction in median clinical seizures relative to baseline during the first four weeks of follow-up, compared to 85% for the first four weeks of the treatment period. Continued significant reductions from baseline in both median long episodes and median clinical seizures in the last four-weeks of follow-up were also observed.

To learn more about rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
Overview of Focal Onset Seizures 00:14
RAP-219 Overview 1:02
Clinical Trial Data 2:29
RAP-219 Dosing Schedules 6:01
Take Home Message 7:00

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Brian Moseley, MD, Senior Medical Director at UCB, discusses the GEMZ clinical trial of fenfluramine in patients with CDKL5 deficiency disorder (CDD).

CDD is a rare genetic disorder characterized by difficult‑to‑control seizures and severe neuro‑developmental impairment. It’s caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome.

At the American Association of Neurology 2026 meeting, primary results were presented from the GEMZ (NCT05064878) clinical trial of fenfluramine in patients with CDD. GEMZ is a phase 3 randomized, double-blind, placebo-controlled, fixed-dose, multicenter study evaluating the safety and efficacy of fenfluramine. Fenfluramine is a phenethylamine that is structurally similar to serotonin that has been proven to be effective in treating pharmacoresistant seizures.

Patients were randomized to fenfluramine 0.7 mg/kg/day or placebo over 14 weeks (including a two week titration period [T] and a 12 week maintenance period [M]). The primary endpoint was countable motor seizure frequency (CMSF) percentage change from baseline over T+M versus placebo.

Safety and modified intent-to-treat populations included 87 and 86 patients, respectively. Most patients received 3 or more concomitant anti-seizure medications. Baseline median CMSF was 44 for patients on fenfluramine and 49 for patients on placebo.

Significant differences in efficacy endpoints were observed with fenfluramine versus placebo. Median percentage CMSF change was −47.6% for fenfluramine versus −2.8% for placebo. A total 45.2% of fenfluramine-treated patients achieved 50% or greater CMSF, compared to 4.5% of placebo patients. Additionally, 38.1% on fenfluramine versus 6.8% on placebo demonstrated clinically meaningful improvement on Clinical Global Impression–Improvement scale. Median percentage change in generalized tonic-clonic seizure frequency from baseline was −61.5% for fenfluramine (n=14) and −13.5% for placebo (n=18).

Four patients discontinued due to treatment-emergent adverse events. Of patients on fenfluramine, the most common adverse events were pyrexia, diarrhea, and somnolence. No new safety signals identified and no valvular heart disease or pulmonary arterial hypertension cases observed.

To learn more about CDD and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
CDKL5 Overview 00:12
GEMZ Clinical Trial Data 1:40
Next Steps 5:16
Targeted Diagnosis and Treatments 5:38
What Physicians Should Know 7:45

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Colin Lake, Head of Digital Business Transformation Neurology at UCB, discusses CareCompass, an online tool for caregivers of patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).

DS is the most severe of a group of conditions known as SCN1A-related seizure disorders. Early signs typically include febrile seizures but as the child continues through childhood, other types of seizures may occur and increase in frequency. Other symptoms include loss of motor skills, intellectual disability, speech impairment, and difficulty with movement. Most cases of Dravet syndrome occur due to mutations within the SCN1A gene.

LGS is another form of severe epilepsy that begins in childhood. It is characterized by multiple types of seizures and intellectual disability. This condition can be caused by brain malformations, perinatal asphyxia, severe head injury, central nervous system infection and inherited degenerative or metabolic conditions. In about one-third of cases, no cause can be found.

Caregivers of patients with DS or LGS face significant financial, physical, and emotional burden due to the demanding nature of these diseases. Of note, caregivers report struggling with fragmented care information across multiple sources that make organization difficult.

CareCompass is a website developed to provide caregivers of individuals with DS or LGS with templates, tools, and emotional support to manage everyday challenges and relieve this burden. Unmet needs of caregivers and providers were identified through focus groups and double-blinded interviews. Once the CareCompass website was designed, a 4 week pilot period was conducted to assess usability, acceptability, and preliminary impact.

Over the 4 week pilot, 21 caregivers participated. Satisfaction was high and caregivers valued having access to essential care details, such as medications, emergency contacts, routines, stored securely in one place. The website allowed for the creation and sharing of care guides, tracking wellbeing, and a journaling feature to log seizure-related and general observations. Participants noted that a mobile app version would also be beneficial.

Through the consolidation of information, CareCompass has the ability to simplify communication and care coordination. Future studies should evaluate the long-term impact of the tool on caregiver burden, confidence, and healthcare system engagement.

To learn more about CareCompass, visit https://care-compass.io/

CHAPTERS
Introduction 00:00
Dravet and LGS Overview 00:36
CareCompass Online Tool 2:01
Take Home Message 7:54

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Dena Sherwood, mother to a neuroblastoma survivor and Founder of Arms Wide Open Childhood Cancer Foundation, discusses CureFest.

Ms. Sherwood and her family founded the Arms Wide Open Childhood Cancer Foundation following the struggles their son experiences with neuroblastoma. The organization provides financial and emotional support for families at any stage of the childhood cancer journey. Some of their programs include funding of research and clinical trials, bereavement retreats, survivor retreats, and CureFest.

CureFest is an annual, three-day event that takes place in Washington, DC and is open to families and patients affected by childhood cancer. The goal of CureFest is to raise awareness, build community, and have lawmakers, clinicians, researchers, and families come together in support of the childhood cancer community and amplify their voices.

This year’s CureFest will be held September 18-20, 2026. For more information, visit https://www.curefestusa.org/.

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Tuan Vu, MD, Professor, Department of Neurology at the University of South Florida, discusses positive results of cemdisiran in patients with generalized myasthenia gravis (gMG).

MG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

Cemdisiran is a RNA interference (RNAi) therapy designed to silence the C5 gene, thereby dampening the complement system that appears to be involved in the pathophysiology of gMG.

Positive results from the phase 3 NIMBLE clinical trial (NCT05070858) of cemdisiran in adults with gMG were recently presented at the 2026 American Academy of Neurology (AAN) Annual Meeting and published in The Lancet. Cemdisiran is a novel siRNA therapeutic designed to durably reduce circulating levels of complement factor 5 (C5). The trial enrolled a total of 123 patients, with 59 in the placebo group and 64 patients treated with subcutaneous cemdisiran every 12 weeks.

Compared to placebo, at week 24, a 4.5-point improvement from baseline on the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score was observed. Notably, 76.6% of cemdisiran-treated patients had a 3-point or greater improvement, versus 44.1% for placebo. Clinically meaningful improvements in MG-ADL total score occurred within 2 weeks in cemdisiran-treated patients.

Additionally, a 4.2-point improvement from baseline in Quantitative Myasthenia Gravis (QMG) total score was observed in the cemdisiran group, versus a 1.5-point improvement in the placebo group. Notably, 48.4% of cemdisiran patients had a 5-point or greater improvement, compared to 19% for placebo. Improvements in QMG total scores occurred within 2 weeks in cemdisiran-treated patients.

The most common AEs were: worsening of MG, upper respiratory tract infection, urinary tract infection, nasopharyngitis, headache, rash, and diarrhea. One or more treatment-emergent adverse events occurred in 69.2% of patients receiving cemdisiran and 77.1% receiving placebo. Most AEs were mild-to-moderate in severity.

To learn more about MG and other rare autoimmune conditions, visit https://checkrare.com/diseases/autoimmune-autoinflammatory-disorders/

CHAPTERS
Introduction 00:00
Myasthenia Gravis Treatment Landscape 00:24
Cemdisiran Overview 1:58
NIMBLE Clinical Trial 3:04
Clinically Meaningful Results 4:52
New Dosing and Effect on Patients 5:46
Take Home Message 6:21

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Daniela Carvalho, MD, MMM, pediatric otolaryngologist at the University of California, San Diego, discusses the approval of Otarmeni (lunsotogene parvec) for the treatment of patients with otoferlin (OTOF)-related hearing loss.

The US Food and Drug Administration (FDA) has granted accelerated approval for Otarmeni (lunsotogene parvec) for the treatment of patients with OTOF-related hearing loss. The indication includes pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant in the same ear.

OTOF-related hearing loss is a rare genetic auditory synaptopathy that results from defective synaptic transmission from normally functioning cochlear inner hair cells to the auditory nerve. The condition typically results in deafness at birth and current management involves cochlear implants.

Lunsotogene parvec, previously known as DB-OTO, is an adeno-associated virus vector-based gene therapy designed to deliver a working copy of the OTOF gene and restore durable, physiological hearing. It is administered via an infusion into the cochlea, similar to the procedure used for cochlear implantation.

The FDA approval is based on results from the CHORD clinical trial (NCT05788536), in which 20 participants, ages 10 months to 16 years, received a single dose of lunsotogene parvec, either unilaterally (n=10) or bilaterally (n=10). The CHORD study is an ongoing, multicenter, open-label, registrational clinical trial evaluating the safety and efficacy of lunsotogene parvec in patients with OTOF-related hearing loss.

Hearing improvements per pure tone audiometry assessments at a threshold of 70 or less dB HL at 24 weeks was observed in 80% of patients. One additional participant achieved this threshold by week 48. Additionally, 70% of patients demonstrated an auditory brainstem response at 90 or less decibels at 24 weeks. At 48 weeks, all prior responders maintained a response to therapy and 42% of participants achieved normal hearing that included whispers.

The most common adverse events in the safety population (n=24) associated with therapy included otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus.

Lunsotogene parvec is the first gene therapy and second new molecular entity approved under the FDA’s National Priority Voucher program. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory portion of the CHORD clinical trial.

CHAPTERS
Introduction 00:00
Otoferlin-Related Hearing Loss Overview 00:45
Limitations to Current Interventions 2:07
Otarmeni Overview 3:04
CHORD Trial Results and Clinical Experience 3:48
Early Diagnosis, Patient Selection, and Referral Pathways 5:33
Take Home Message 7:01

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