Firdapse (amifampridine) / BioMarin, Catalyst Pharma, Dydo Pharma - LARVOL DELTA

To Treat or Not To Treat - Immune Checkpoint Inhibition in Patients with SCLC-associated LEMS (SNO 2025) - "He was started on carboplatin, etoposide, and atezolizumab after which his weakness and diplopia worsened...One year later, she was found to have brain metastasis treated with stereotactic radiosurgery and durvalumab... Additional data is needed to better understand the safety of ICI in SCLC-associated LEMS."

Checkpoint inhibition • Clinical • CNS Disorders • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

To Treat or Not To Treat - Immune Checkpoint Inhibition in Patients with SCLC-associated LEMS (WFNOS 2025) - "He was started on carboplatin, etoposide, and atezolizumab after which his weakness and diplopia worsened...One year later, she was found to have brain metastasis treated with stereotactic radiosurgery and durvalumab... Additional data is needed to better understand the safety of ICI in SCLC-associated LEMS."

Checkpoint inhibition • Clinical • CNS Disorders • Lung Cancer • Small Cell Lung Cancer • Solid Tumor

UNMASKING LEMS: A CASE OF LAMBERT-EATON MYASTHENIC SYNDROME IN THE CONTEXT OF MULTIPLE SCLEROSIS (CHEST 2025) - "The patient initiated radiation with adjuvant chemotherapy of carboplatin and etoposide...First-line treatment consists of cancer-directed treatment, if indicated, as well as the potassium-channel blocker amifampridine phosphate, which serves to enhance acetylcholine release at the neuromuscular junction. This case highlights the importance of careful neurologic examination for consideration of LEMS in patients with underlying neurologic conditions. Early recognition and appropriate management, including treatment of possible underlying malignancy such as SCLC, are critical to improving patient outcomes in this population."

Clinical • CNS Disorders • Cough • Gastrointestinal Disorder • Lung Cancer • Multiple Sclerosis • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • Xerostomia • CRP

Exploring a gap of the 2024 McDonald criteria: the role of two spinal cord lesions plus oligoclonal bands, and transverse spinal cord lesion extent, in patients with a typical attack onset (ECTRIMS 2025) - "Luca Bollo has received a Rio Hortega grant, from the Instituto de Salud CarlosIII, Spain (CM24/XXX) and a one-year stipend endowed by the NMSS/AAN John Dystel Prize for Multiple Sclerosis Research awarded to Prof...Xavier Montalban's institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings, clinical trial steering committee membership, or clinical advisory board participation in recent years from Abbvie, Actelion, Alexion, Astrazeneca, Autolus, Bial PD, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Indivi, Janssen Pharmaceuticals,Juvisé Pharmaceutical, Lilly, Medday, Medscape, Merck, Mylan-Viatris, Nervgen, Neuraxpharm, Novartis, Peervoice, Rewind Therapeutics, Samsung-Biosys, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Zenas Biopharma, Excemed, ECTRIMS, MSIF, and NMSS or any of their affiliates... A transverse lesion extent =2 SC..."

Clinical • Late-breaking abstract • CNS Disorders • Multiple Sclerosis

Exploring early RAW and early PIRA as definitions of aggressive multiple sclerosis and as combined predictors of confirmed EDSS 4.0 at 5 years (ECTRIMS 2025) - "Luca Bollo has received a Rio Hortega grant, from the Instituto de Salud CarlosIII, Spain (CM24/XXX) and a one-year stipend endowed by the NMSS/AAN John Dystel Prize for Multiple Sclerosis Research awarded to Prof...Xavier Montalban's institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings, clinical trial steering committee membership, or clinical advisory board participation in recent years from Abbvie, Actelion, Alexion, Astrazeneca, Autolus, Bial PD, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Indivi, Janssen Pharmaceuticals,Juvisé Pharmaceutical, Lilly, Medday, Medscape, Merck, Mylan-Viatris, Nervgen, Neuraxpharm, Novartis, Peervoice, Rewind Therapeutics, Samsung-Biosys, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Zenas Biopharma, Excemed, ECTRIMS, MSIF, and NMSS or any of their affiliates... We found associations of older..."

Late-breaking abstract • CNS Disorders • Multiple Sclerosis

Firdapse for Post-BOTOX Vocal Weakness (clinicaltrials.gov) - P2 | N=18 | Completed | Sponsor: Augusta University | N=10 ➔ 18 | Trial completion date: Dec 2023 ➔ Sep 2025 | Trial primary completion date: Dec 2023 ➔ May 2025 | Recruiting ➔ Completed

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Dysphonia

Diagnostic Performance of Paramagnetic Rim Lesions in Multiple Sclerosis in a Large, Prospective, Multicenter Cohort: Insights from the CAVS-MS Study (ECTRIMS 2025) - "Christina J Azevedo: Received consulting fees from Genentech, Zenas Biopharma, EMD Serono, Alexion Pharmaceuticals, Sanofi Genzyme... Our findings from the largest, prospective, international study on diagnostic performance of PRL in MS support the inclusion of PRL in the 2024 McDonald Criteria by demonstrating PRL as a broadly applicable imaging biomarker with high diagnostic specificity (particularly if multiple) and sensitivity (as a potential substitute for dissemination in space). We anticipate that sensitivity and specificity of baseline PRL will increase with ongoing follow-up of the CAVS-MS cohort, which will also enable definitive validation of baseline PRL as a valuable diagnostic biomarker. Disclousure of interest: Joshua D Lee: Nothing to disclose."

Clinical • Late-breaking abstract • CNS Disorders • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Multiple Sclerosis • Rheumatology

A Phase 2, Open Label, Sequential Group, Investigator Blinded Study ofMagnetic Resonance Spectroscopy (to Assess the Effects ofCNM-Au8 for the Bioenergetic Improvement of Impaired Neuronal RedoxState in Multiple Sclerosis (REPAIR-MS) - Results (ECTRIMS 2025) - " REPAIR-MS cohort 1 included relapsing remitting MS, stable on natalizumab...Sguigna received personal compensation for consulting services from Genentech, EMD Serono, Horizon Therapeutics, Amgen, and Bristol Myers Squibb and has received research support from Genentech, Clene Nanomedicine, Zenas Biopharma, IPMSA through the NMSS, PCORI, DOD/CDMRP, and NIH/NIA through his institution... CNM-Au8 showed evidence of improved brain bioenergetics improvement in MS participants with an average percent increase in the NAD+/NADH ratio of 9.5% (p=0.0275). CNM-Au8 treatment was safe and well-tolerated with treatment emergent adverse events predominantly assessed as mild-to-moderate severity, and transient. This data buttresses the theory that bioenergetic failure contributes to neurodegeneration in MS."

Clinical • Late-breaking abstract • P2 data • CNS Disorders • Movement Disorders • Multiple Sclerosis • Parkinson's Disease

AGNOS: A Phase 4 Study of Ofatumumab in Treatment-Naïve Participants with Very Early Relapsing-Remitting Multiple Sclerosis Compared with Healthy Controls (ECTRIMS 2025) - "Darin T Okuda has received personal compensation for consulting and advisory services from Biogen Inc., Cortechs.AI, Eisai, EMD Serono, Genentech, Genzyme/Sanofi, Immunic Therapeutics, Moderna, Octave Bioscience, Pfizer, and Zenas BioPharma along with research support from Alexion and Novartis... This pre-planned analysis confirms the efficacy of OMB in participants with very early, recently diagnosed, treatment-naïve RRMS in the AGNOS study, with over 80% of participants achieving NEDA-3 from months 6 to18. Functional performance and imaging outcomes in OMB-treated participants appeared broadly similar to those observed in healthy controls up to 18 months. Safety findings were consistent with prior reports."

Clinical • Late-breaking abstract • P4 data • CNS Disorders • Fatigue • Infectious Disease • Multiple Sclerosis • Musculoskeletal Pain • Novel Coronavirus Disease

Epidemiological analysis of Lambert-Eaton myasthenic syndrome in Türkiye: insights from a nationwide electronic health database. (PubMed, Front Neurol) - "In this study, we aimed to determine the epidemiological profile of LEMS in Türkiye, and to assess associated malignancies, mortality, and prescription rates of pyridostigmine and amifampridine...This is the first nationwide epidemiological study of LEMS in Türkiye, revealing lower incidence and prevalence rates than in other countries. This study provides valuable large-scale epidemiological data, enriching the global understanding of this rare disorder."

Journal • Immunology • Lung Cancer • Oncology • Rare Diseases • Small Cell Lung Cancer • Solid Tumor

Lambert Eaton Myasthenic Syndrome. (PubMed, Int Rev Neurobiol) - "Treatment of LEMS comprises symptomatic treatments such as 3,4 diaminopyridine (amifampridine), which increases quantal release; immunotherapy; and treatment of underlying malignancy if present. The life expectancy of non-tumour LEMS is normal, although complete remission is uncommon. Progression of SCLC determines prognosis in tumour-associated LEMS, which is nonetheless better than in SCLC without LEMS."

Journal • Review • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Xerostomia

The recognition, physiology, and treatment of Lambert-Eaton myasthenic syndrome. (PubMed, Dis Mon) - "There are effective treatments for symptoms of LEMS that work directly at the neuromuscular junction, as well as treatments for the cancer if present. Various types of immunosuppression can be beneficial for both paraneoplastic (T LEMS) and non-tumor LEMS (NT LEMS)."

Journal • Erectile Dysfunction • Hypotension • Immunology • Lung Cancer • Myasthenia Gravis • Oncology • Rare Diseases • Small Cell Lung Cancer • Solid Tumor • Xerostomia

Kye Pharmaceuticals Receives Health Canada Approval for New Dosing Guidance for FIRDAPSE and an additional Pediatric Indication (Canada Newswire) - " Kye Pharmaceuticals, Inc. ('Kye') today announced that Health Canada has approved its SNDS (Supplemental New Drug Submission) regarding the recommended dosage of FIRDAPSE (amifampridine) for adults to include that some patients may benefit from a total daily dose of 100mg for the treatment of Lambert-Eaton myasthenic syndrome ('LEMS'). The direction that some patients may benefit from an increased maximum daily dose of up to 100 mg offers healthcare providers and patients greater flexibility in treatment regimens for the management of LEMS. The expanded indication includes pediatric dosing guidance for patients 6 years of age and older and offers pediatric neurologists a proven treatment option for children diagnosed with LEMS."

Canadian regulatory • Immunology

Long-term Efficacy and Safety of Amifampridine Phosphate (Firdapse®) in Japanese Patients with Lambert-Eaton Myasthenic Syndrome (LMS-005 Study). (PubMed, Intern Med) - "Five patients in the safety population experienced adverse drug reactions, the most common of which was dysesthesia (n=2). Conclusion This study revealed the long-term efficacy and tolerability of amifampridine phosphate in Japanese adults with LEMS."

Journal • CNS Disorders • Myasthenia Gravis

Safety and Efficacy of Frexalimab from the Phase 2 Open-label Extension in Participants with Relapsing Multiple Sclerosis: 2-year Results (S3.006). (PubMed, Neurology) - P2 | "Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Bristows . Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff."

Clinical • Journal • P2 data • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Pain • CD40LG

Colitis in Multiple Sclerosis Patients Treated with B-cell Depleting Monoclonal Antibodies (P8-1.014). (PubMed, Neurology) - "We selected cases of MS patients who treated with rituximab and/or ocrelizumab subsequently developed gastrointestinal symptoms consistent with colitis...Ionete has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Zenas...Hemond has received personal compensation in the range of $0-$499 for serving as a Member of Data Safety and Monitoring Board with National Institute Of Neurological Disorders And Stroke of the National Institutes of Health. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff."

Journal • Retrospective data • Cardiovascular • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis

Selective Radiological Vulnerability and Neuropsychiatric Challenges in Anti-DPPX Antibody-Associated Encephalitis (P10-8.003). (PubMed, Neurology) - "To report the 66th published case of dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, describe the clinical and radiological trajectory, and therapeutic response to plasmapheresis followed by rituximab...Tolerability complaints related to prescribed anticonvulsants (levetiracetam, zonisamide), compounded by neuropsychiatric symptoms, including persistent irritability and unfiltered verbal expressions, contributed to treatment noncompliance and repeated hospitalizations...Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Zenas BioPharma...Dr. Okuda has received intellectual property interests from a discovery or technology relating to health care."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Lupus • Multiple Sclerosis • Psychiatry • Systemic Lupus Erythematosus

Catalyst Pharmaceuticals Announces Sub-Licensee DyDo Pharma Launched FIRDAPSE in Japan (GlobeNewswire) - "Catalyst Pharmaceuticals, Inc...today reported that its sub-licensee in Japan, DyDo Pharma, Inc., ('DyDo') has launched FIRDAPSE (amifampridine) Tablets 10 mg in Japan for the indication of improving muscle weakness in patients living with Lambert-Eaton myasthenic syndrome ('LEMS')."

Launch non-US • Immunology

LOOKING VERY HARD FOR A CAUSE OF LAMBERT-EATON MYASTHENIC SYNDROME. (WRMC 2025) - "The patient was started on amifampridine, a novel potassium channel blocker agent, at 30mg daily and titrated upwards slowly up to 20mg three times daily. Intravenous immunoglobulin (IVIg), pyridostigmine 60mg, and prednisone 5mg were added...Perhaps one can never look too hard to find a tumor in LEMS, even if NT-LEMS is diagnosed. Figure 1: PET whole body approximately 6 months post diagnosis of Non-Paraneoplastic Lambert-Eaton Myasthenic Syndrome, showing SUV max of 7.4 in the area of the right colon (red arrow)."

Colon Cancer • Colorectal Cancer • Dry Eye Disease • Fatigue • Giant Cell Arteritis • Hematological Disorders • Hematological Malignancies • Immunology • Lung Cancer • Multiple Myeloma • Musculoskeletal Pain • Myasthenia Gravis • Oncology • Ophthalmology • Pain • Rheumatology • Small Cell Lung Cancer • Solid Tumor • Xerostomia

Effect of Amifampridine on Neuromuscular Transmission in Patients Treated With OnabotulinumtoxinA (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Wake Forest University Health Sciences | Recruiting ➔ Completed

Trial completion

LEMS Update (ICNMD 2024) - "Amifampridine is the first choice symptomatic treatment, while also a beneficial effect of pyridostigmine has been reported...Anti-CD 20 antibody therapies or CAR-T cell therapies might be interesting options for patients that are more difficult to treat. Importantly, LEMS is one of the rare autoimmune disorders with a well-defined pathogenesis due to a well-known autoantibody, which facilitates detailed studies of the effect of new drugs."

CNS Disorders • Immunology • Myasthenia Gravis • Oncology

Effect of Amifampridine on Neuromuscular Transmission in Patients Treated With OnabotulinumtoxinA (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Wake Forest University Health Sciences | Trial primary completion date: Sep 2024 ➔ Dec 2024

Trial primary completion date

Catalyst Pharmaceuticals Announces Sub-Licensee DyDo Pharma Received Approval to Commercialize FIRDAPSE in Japan (GlobeNewswire) - "Catalyst Pharmaceuticals, Inc...announced that its sub-licensee in Japan, DyDo Pharma, Inc., ('DyDo') has reported that the Ministry of Health, Labor and Welfare of Japan has approved DyDo's New Drug Application ('NDA') to commercialize FIRDAPSE (amifampridine) Tablets 10 mg for treatment of patients with Lambert-Eaton Myasthenic Syndrome ('LEMS') in Japan. This approval marks a pivotal advancement in the treatment of LEMS, a rare autoimmune disorder that can severely impact quality of life and represents a significant step forward in addressing the unmet needs of patients affected by LEMS in Japan."

Japan approval • Immunology

Effect of Amifampridine on Neuromuscular Transmission in Patients Treated With OnabotulinumtoxinA (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Wake Forest University Health Sciences | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Trial completion date • Trial primary completion date

Amifampridines are the Most Effective Drugs for Treating Lambert-Eaton Myasthenic Syndrome With a Focus on Pediatric Lambert-Eaton Myasthenic Syndrome. (PubMed, J Clin Neurol) - "In two patients with 3,4-DAPP, significant improvement in one and no improvement in one. Amifampridines are proven to be effective and safe drugs for the symptomatic treatment without serious side reaction in adults as well as in children as long as the dosage is properly adhered."

Journal • Review • Infectious Disease • Myasthenia Gravis • Oncology • Pediatrics