Therapeutic advances in rare disease最新文献

{"title":"Current therapeutic landscape of β-thalassemia: focus on gene therapy.","authors":"Aaron N Cheng, Janet L Kwiatkowski","doi":"10.1177/26330040261433028","DOIUrl":"10.1177/26330040261433028","url":null,"abstract":"<p><p>β-thalassemia is an inherited blood disorder characterized by chronic anemia, ineffective erythropoiesis, and in its most severe form, lifelong transfusion dependence. The standard of care for transfusion-dependent thalassemia (TDT) is regular red blood cell transfusions to relieve the anemia and suppress ineffective erythropoiesis and iron chelation therapy to mitigate morbidity and mortality related to iron overload. Allogeneic hematopoietic stem cell transplantation is a curative option but is only available to patients with an appropriate donor and carries risks of graft-versus-host disease and other transplant-related morbidity. In recent years, the therapeutic landscape for TDT has changed dramatically with the approval of two autologous gene therapies in the United States: betibeglogene autotemcel (beti-cel) and exagamglogene autotemcel (exa-cel). Clinical trials for both gene therapies have demonstrated high rates of sustained transfusion independence for both pediatric and adult age groups. However, despite these advances, challenges remain. Gene therapy requires myeloablative busulfan-based conditioning chemotherapy, which carries the risk of short- and long-term toxicities. Furthermore, centralized manufacturing and high treatment costs are likely to limit access to gene therapy. In this review, we discuss the available clinical trial and real-world data for beti-cel and exa-cel. We describe how gene therapy fits into the current treatment landscape and introduce areas of ongoing investigation to improve access to transformative therapy for TDT.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261433028"},"PeriodicalIF":0.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could an outcome-based agreement be operationalized using real-world data from the Canadian Neuromuscular Disease Registry? Perspectives from an expert-led assessment in spinal muscular atrophy.","authors":"Arif Mitha, Victoria Hodgkinson, Susi Vander Wyk, Chris Cameron, Allison Wills","doi":"10.1177/26330040261433035","DOIUrl":"10.1177/26330040261433035","url":null,"abstract":"<p><strong>Background: </strong>Outcome-based agreements (OBAs) may facilitate earlier patient access to promising therapies, particularly when evidence is limited. The authors of this paper investigated how to operationalize an OBA using real-world data (RWD) from the Canadian Neuromuscular Disease Registry (CNDR).</p><p><strong>Objective: </strong>The first objective of this research was to determine which spinal muscular atrophy (SMA) health outcomes in the CNDR are suitable for an OBA. The second objective was to evaluate the current process of data collection in the CNDR and explore how to operationalize data processes to support an OBA, including identifying gaps and proposing solutions.</p><p><strong>Design: </strong>This qualitative expert-led assessment was conducted through a series of focus group discussions with selected experts.</p><p><strong>Methods: </strong>A selected group of experts participated in 17 focus group meetings. The ability of the CNDR to generate real-world evidence (RWE) for an OBA was evaluated for eight SMA health outcomes. The criteria used were data readiness, interpretability, and timeframe within the CNDR. Next, the processes involved were evaluated, specifically to determine how data tracking within the CNDR could be operationalized for an OBA, including identifying gaps and possible solutions. Based on the findings, the group proposed a future state for an OBA process using the CNDR. The group followed up with stakeholder feedback interviews to validate the findings of this research and to gather insights.</p><p><strong>Results: </strong>Five SMA outcomes within the CNDR were identified as potentially suitable outcomes for OBA. Three process gaps were identified in the current state of the CNDR, and corresponding solutions were proposed. A proposed future-state process flow for CNDR was developed to support RWE generation for OBA.</p><p><strong>Conclusions: </strong>Expert consultations suggest that operationalizing an OBA using CNDR RWD is feasible.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261433035"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliability assessment using the test-retest method and minimal important changes in the Adult Fabry Disease Quality of Life Scale.","authors":"Yuta Koto, Masami Tanaka, Mitsuyo Ishiura, HyeSook Kim, Atsushi Ohashi, Nozomi Hadano, Aya Narita, Norio Sakai","doi":"10.1177/26330040261433034","DOIUrl":"10.1177/26330040261433034","url":null,"abstract":"<p><strong>Background: </strong>Fabry disease is rare and multisystemic, necessitating a disease-specific quality of life scale to assess changes in quality of life. We developed the Adult Fabry Disease Quality of Life scale to measure the quality of life of adult patients with Fabry disease.</p><p><strong>Objectives: </strong>To confirm the reliability of the Adult Fabry Disease Quality of Life scale using the test-retest method and calculate the minimal important change.</p><p><strong>Design: </strong>This study was based on two questionnaire surveys conducted at approximately 2-week intervals in November and December 2024 in Japan.</p><p><strong>Methods: </strong>Twenty-eight participants completed questionnaires consisting of background information, the Adult Fabry Disease Quality of Life scale, and the Short Form-8. In the second survey, an anchor question with a 7-point Likert scale was added to assess changes in general health. The intraclass correlation coefficient for reliability and Cronbach's alpha coefficient for internal consistency were calculated. For minimal important changes, the average value of the smallest change group for the anchor question was calculated.</p><p><strong>Results: </strong>The intraclass correlation coefficients for each factor and the total score on the Adult Fabry Disease Quality of Life scale were 0.892-0.946. Cronbach's alpha coefficient was 0.948 for the first survey and 0.956 for the second. In response to the anchor question, three participants (13.0%) felt a little worse, and three (13.0%) felt a little better. Those who felt a little worse and those who felt a little better showed improvements in quality of life of 3.7 and 5.3 points, respectively.</p><p><strong>Conclusion: </strong>The Adult Fabry Disease Quality of Life scale is highly reproducible at 2-week intervals. Defining the minimum important change was not possible, which is important when used as an outcome. Future studies should establish it using the anchor method.</p><p><strong>Trial registration: </strong>This prospective study was registered with the UMIN-CTR on September 1, 2024 (No. UMIN000055144).</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261433034"},"PeriodicalIF":0.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and opportunities for the use of telehealth in rare disease diagnosis, treatment, research, and education: key opinion leader interviews by the IRDiRC telehealth task force.","authors":"Melissa A Parisi, Adam L Hartman, Mary Catherine V Letinturier, Elena-Alexandra Tataru, Victoria Antoniadou, Gareth Baynam, Lara Bloom, Marco Crimi, Maria G Della Rocca, Giuseppe Didato, Sofia Douzgou Houge, Anneliene H Jonker, Martina Kawome, Friederike Mueller, James O'Brien, Ratna Dua Puri, Nuala Ryan, Meow-Keong Thong, Birutė Tumienė, Faye H Chen","doi":"10.1177/26330040261427023","DOIUrl":"10.1177/26330040261427023","url":null,"abstract":"<p><p>The International Rare Diseases Research Consortium (IRDiRC) Telehealth (TH) Task Force explored the use of TH for improving diagnosis, care, research, and education for rare diseases (RDs) worldwide. The Task Force members interviewed 23 key opinion leaders (KOLs), providing perspectives from experts in the use of TH for the diagnosis, treatment, and prevention of RDs (10 KOLs); for research and evaluation in RDs (7); and for the continuing education of health care providers (HCPs) in RDs (6). The KOLs represented a broad array of diverse perspectives with regard to both geographic regions, including Europe, United States, Sub-Saharan Africa, and Asia, and professional expertise, including rare disease patients and family members, RD association spokespersons, TH association representatives, physicians, researchers, and regulatory authorities. The Task Force solicited KOL opinions to identify factors that influence TH in improving access to diagnosis, care, prevention, and research experiences for RD patients and providers as well as continuing education and peer mentoring for HCPs. This manuscript represents a synthesis of those interviews and some common themes that emerged, along with identification of evidence and knowledge gaps that will benefit from future research efforts to help advance and expand the use of TH for RD care, research, and education. KOLs agreed on the unique elements of RD medical care that could benefit from TH approaches and recognized the increasing role that remote assessments can play in supporting RD research. They identified models for health care provider education afforded by TH that can enhance care for RD patients and broaden the pool of experts in these conditions. While recognizing that barriers to broad implementation exist, they agreed that TH provides a unique tool to provide greater access to care for RD patients worldwide.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261427023"},"PeriodicalIF":0.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient and caregiver perspectives on neurodevelopmental and mental health care for RASopathies.","authors":"Evelyn M Elizondo, Anne M Floyd, Allison M H Foy, Dante J Rogers, Betül Çakır-Dilek, Megan Manternach, Jessica Simacek, Rebekah L Hudock, Elizabeth I Pierpont","doi":"10.1177/26330040261427019","DOIUrl":"https://doi.org/10.1177/26330040261427019","url":null,"abstract":"<p><strong>Background: </strong>Clinical studies have begun to evaluate therapeutic approaches to address the widespread neurodevelopmental and mental health challenges associated with a group of genetic syndromes known as \"RASopathies.\" However, the perspectives of patients and families regarding the relevance and accessibility of such treatment approaches have not been studied.</p><p><strong>Objectives: </strong>To assess the mental healthcare needs and treatment experiences encountered by individuals with RASopathies and caregivers.</p><p><strong>Design: </strong>Directed content analysis of focus group and interview transcripts.</p><p><strong>Methods: </strong>We qualitatively analyzed data from four virtual focus groups comprised of caregivers (<i>n</i> = 21) of youth with RASopathies and a series of individual interviews with young adults (<i>n</i> = 11) with RASopathies. Perspectives on primary neurodevelopmental and mental health concerns, treatment history, and care accessibility were explored using a directed content analysis framework.</p><p><strong>Results: </strong>Consistent with prior research, participants reported that attention/executive functioning, mood, and social concerns were common; anxiety was a particularly frequent comorbidity. Mental health concerns varied across settings and frequently interfaced with physical health symptoms. Barriers to care included poor accessibility of services, adverse medication effects, and a lack of provider experience or knowledge. Addressing neurodevelopmental and mental health symptoms effectively often necessitates family resilience and advocacy on the part of patients and their caregivers. Emergent themes uncovered needs for provider training pertaining to rare diseases, trauma-informed care, and improved community awareness regarding RASopathies.</p><p><strong>Conclusion: </strong>This study identified a set of actionable items to inform research, care delivery, and advocacy that reflect the expressed needs and lived experiences of participants representing both caregivers and patients with RASopathies.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261427019"},"PeriodicalIF":0.0,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel therapy for pyridoxine-dependent epilepsy due to biallelic pathogenic variants in <i>ALDH7A1</i>: secondary mitochondrial energy deficiency and improvements of neurodevelopmental outcomes on triheptanoin treatment.","authors":"Anastasia Ambrose, Morganne McCabe, Shalini Bahl, David Sinasac, Thomas Snyder, Saadet Mercimek-Andrews","doi":"10.1177/26330040261427020","DOIUrl":"https://doi.org/10.1177/26330040261427020","url":null,"abstract":"<p><strong>Background: </strong>Pyridoxine-dependent epilepsy (PDE) due to biallelic pathogenic variants in <i>ALDH7A1</i> (PDE-ALDH7A1) is an metabolic disease of lysine catabolism. Current standard treatment includes pyridoxine, arginine, and lysine- or protein-restricted diet. Pyridoxine treats seizures. Arginine and lysine- or protein-restricted diet decrease elevated α-aminoadipic semialdehyde (α-AASA) and Δ1- piperideine-6-carboxylate (P6C) levels to improve neurodevelopmental outcomes. We previously reported abnormalities in tricarboxylic acid (TCA) cycle and electron transport chain in PDE-ALDH7A1. We report a new patient with PDE-ALDH7A1 who did not show any improvements in neurodevelopment on the current standard therapy. We hypothesized that triheptanoin will provide substrate to TCA cycle and improve abnormal energy metabolism leading to improvements in neurodevelopmental outcome.</p><p><strong>Objective: </strong>To treat this patient with triheptanoin to improve neurodevelopmental outcome.</p><p><strong>Design: </strong>Due to complex I deficiency and lack of response to the current standard therapy, we applied triheptanoin novel therapy.</p><p><strong>Methods: </strong>A 4-year-old male had compound heterozygous variants in <i>ALDH7A1</i> and markedly elevated urine α-AASA. The goal dose of triheptanoin was 50% of the estimated energy requirement (EER). We assessed efficacy of triheptanoin using neuropsychological assessments. We measured 6-oxopipecolic acid using liquid chromatography tandem mass spectrometry.</p><p><strong>Results: </strong>Triheptanoin was started at 10 mL/day. There was nausea up to 3 weeks after each dose increase, which has improved allowing us to increase triheptanoin gradually. The maximum actual dose of triheptanoin was 40% of EER. Cognitive composite score improved from 16% to 63% on treatment. All chemistry and biochemical investigations were normal. 6-oxopipecolic acid levels did not normalize. Triheptanoin treatment seemed to be safe and tolerated well.</p><p><strong>Conclusion: </strong>Triheptanoin is an anaplerotic agent to provide substrates to the TCA cycle. This novel therapy improved neurodevelopmental outcome in our patient with PDE-ALDH7A1. We think that trihepatonoin should be the part of the current standard therapy to improve neurodevelopmental outcomes in patients with PDE-ALDH7A1.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261427020"},"PeriodicalIF":0.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PBC Ireland patient registry: study protocol for a national platform on primary biliary cholangitis.","authors":"Gerry Nesbitt, Alexandra Curley","doi":"10.1177/26330040261427491","DOIUrl":"https://doi.org/10.1177/26330040261427491","url":null,"abstract":"<p><strong>Background: </strong>Primary Biliary Cholangitis (PBC) is a chronic, progressive liver disease. This paper outlines how a PBC patient registry was developed to address the gaps in evidence, care and policy affecting PBC patients in Ireland.</p><p><strong>Objectives: </strong>The PBC patient registry is designed to collect patient-reported data regarding medical history, pruritus, fatigue and quality of life of PBC patients living in Ireland. This data can be used to identify care and treatment gaps and ensure that the PBC patient voice is included in new treatment decisions and healthcare policy. This real-world data will support further scientific and clinical research, drive patient-led advocacy efforts and facilitate collaboration with the liver disease communities globally.</p><p><strong>Design: </strong>A patient-led, observational, registry-based study of PBC patients in Ireland.</p><p><strong>Methods and analysis: </strong>Participants must have a PBC diagnosis and be 18 years of age or older. PROMs (patient-reported outcome measures) were administered through a secure web-based system. After providing electronic informed consent, participants completed online data collection forms. These included demographic information, medical history, standard of care and validated PROMs for fatigue, pruritus and quality of life. This was followed by an anonymous survey to collect usability and comprehensiveness metadata.</p><p><strong>Ethics: </strong>The protocol was approved by TIER IRB Services, protocol ID: 5250715 (July 18th, 2025), which determined the study to be exempt as an observational, minimal-risk, non-interventional research activity involving anonymised patient-reported data.</p><p><strong>Discussion: </strong>At the time of publication, 52 participants were registered in the patient registry, of which 40 completed all data collection forms. The results of the post-completion survey suggest high satisfaction across the domains of usability, comprehension, relevance, privacy/confidentiality and overall experience. The PBC patient registry shows that web-based PROMs can be used to collect real-world evidence from patients. Participants reported that the system was easy to use and comprehensive, confirming the usability and effectiveness of this approach. It also provides a starting point to identify healthcare and treatment gaps and facilitates the inclusion of PBC patients' voices in national and international health policy decisions that affect them.</p><p><strong>Trial registration: </strong>Not applicable.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261427491"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Miglustat: a first-in-class enzyme stabilizer for cipaglucosidase alfa for the treatment of late-onset Pompe disease.","authors":"Robert J Hopkin, Barry J Byrne, Mazen M Dimachkie, Priya S Kishnani, Tahseen Mozaffar, Mark Roberts, Benedikt Schoser, Nadine A M E van der Beek, Ans T van der Ploeg, Stephan Wenninger, Jon Brudvig, Brian Fox, Fred Holdbrook, Vipul Jain, Franklin Johnson, Jennifer Zhang, Giancarlo Parenti","doi":"10.1177/26330040261425686","DOIUrl":"https://doi.org/10.1177/26330040261425686","url":null,"abstract":"<p><p>Late-onset Pompe disease (LOPD) is a rare inherited disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to an accumulation of lysosomal glycogen in tissues, profoundly affecting muscles. Patients with LOPD typically have some residual GAA activity but experience progressive skeletal muscle dysfunction resulting in muscle weakness and respiratory failure. Enzyme replacement therapy (ERT) with alglucosidase alfa, a recombinant human GAA (rhGAA), was the first disease-specific therapy for Pompe disease. Despite efficacy in the first years of use, many patients receiving alglucosidase alfa experience a decline in function over time. This may reflect the inherent challenges associated with rhGAA ERT, such as enzyme inactivation at the near-neutral pH of blood, inefficient target cell uptake, and a necessity for complete lysosomal processing once inside target cells. Cipaglucosidase alfa, a second-generation rhGAA, aims to address these challenges through natural enrichment with bis-mannose-6-phosphate-containing <i>N</i>-glycans to enhance cellular uptake while retaining capacity for complete postdelivery processing. Co-administration of cipaglucosidase alfa with the small molecule stabilizer miglustat (N-butyldeoxynojirimycin) enhances cipaglucosidase alfa stability in the bloodstream after infusion. We discuss published and new preclinical and clinical data on the efficacy and safety of miglustat in combination with cipaglucosidase alfa for treating LOPD. Studies in Pompe mouse models and patients with Pompe disease showed that stabilization by miglustat improved cipaglucosidase alfa exposure and availability for uptake into target tissues and was associated with improved functional outcomes and biomarker levels compared with cipaglucosidase alfa alone. In patients with Pompe disease, the once every 2 weeks dosing regimen of miglustat was well tolerated, with a low frequency of miglustat-related gastrointestinal events compared with daily miglustat regimens at higher doses used in the treatment of other diseases. <b><i>Trial registration</i>:</b> New data are reported for NCT02675465 (ATB200-02), NCT03729362 (PROPEL), and NCT04138277 (PROPEL open-label extension, ATB200-07); all registered at ClinicalTrials.gov (https://clinicaltrials.gov).</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261425686"},"PeriodicalIF":0.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of home administration of cipaglucosidase alfa plus miglustat in late-onset Pompe disease: results from multiple clinical trials.","authors":"Henning Andersen, Jordi Díaz-Manera, Ozlem Goker-Alpan, Tahseen Mozaffar, Sheela Sitaraman Das, Brian Fox, Farah Amon, Kinesha O'Brien-Prince, Mitchell Goldman, Fred Holdbrook, Vipul Jain, Barry J Byrne","doi":"10.1177/26330040261416943","DOIUrl":"10.1177/26330040261416943","url":null,"abstract":"<p><strong>Background: </strong>Late-onset Pompe disease (LOPD) is caused by a deficiency of the acid α-glucosidase enzyme. In LOPD treatment, enzyme replacement therapy is delivered via intravenous infusion, typically in clinical settings. Cipaglucosidase alfa is delivered with the oral enzyme stabilizer miglustat (cipa + mig).</p><p><strong>Objectives: </strong>Evaluate the safety of cipa + mig home infusions.</p><p><strong>Design: </strong>Post hoc analysis of pooled safety data from three clinical trials in adults with LOPD (NCT02675465, NCT03729362, NCT04138277).</p><p><strong>Methods: </strong>The frequency and severity of infusion-associated reactions (IARs) during cipa + mig home and clinic administration were analyzed.</p><p><strong>Results: </strong>In total, 65/151 patients (43.0%) received ⩾1 cipa + mig home treatment. Of 9185 treatments, 2024 (22.0%) were administered at home. IAR frequency was similar for home (1.3%, 26/2024) and clinic (1.8%, 129/7161). The most frequent IAR following home infusion was pyrexia (6.2% of patients). Two patients with ⩾1 home-based treatment experienced serious IARs.</p><p><strong>Conclusion: </strong>Analyses support the safety of home cipa + mig treatment in eligible adults with LOPD.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"7 ","pages":"26330040261416943"},"PeriodicalIF":0.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From care to cure: a patient engagement framework for rare disease and orphan drug research.","authors":"Nahya Awada, Anil Varughese","doi":"10.1177/26330040251404519","DOIUrl":"10.1177/26330040251404519","url":null,"abstract":"<p><strong>Background: </strong>Rare diseases (RDs) encompass over 6000-8000 conditions, with 94% lacking available therapies. These conditions affect 400 million people globally, including three million Canadians, who face numerous challenges throughout their healthcare journey. Patient engagement (PE) is increasingly recognized as essential for improving outcomes yet remains inadequate in RD and orphan drug research particularly in Canada, where a national strategy for integrating RD patients' perspectives is lacking. To address this gap, this paper presents a Rare Disease Patient Engagement Framework (RDPEF), a structured model designed to support meaningful PE across all levels of healthcare, including research.</p><p><strong>Objectives: </strong>To develop a RDPEF that addresses barriers to engagement, reduces stigma, and incorporates patient experience as a core element in RD and orphan drug research and decision-making.</p><p><strong>Design: </strong>A conceptual framework development study informed by qualitative research and a targeted review of existing PE frameworks.</p><p><strong>Methods: </strong>The RDPEF was developed using a systematic approach that combined a review of existing literature on PE frameworks with new qualitative research on the experiences of RD patients in Canada. Semi-structured interviews examined patients' healthcare journeys, focusing on disease management, access to orphan drugs, and opportunities for engagement. A thematic analysis of the existing literature and interview data identified common challenges, which guided the framework's design. The RDPEF integrates elements from various other PE models, customizes them to the specific needs of RD patients, and emphasizes engagement across the entire orphan drug lifecycle.</p><p><strong>Results: </strong>Thematic findings from qualitative research highlighted limited to no patient involvement beyond clinical trials, significant stigma and discrimination, and the absence of structured engagement in drug review and reimbursement processes. These insights informed the development of the RDPEF, which outlines levels and forms of engagement, guiding principles (including stigma reduction), and mechanisms for integrating patient experience across healthcare, policy, and research domains.</p><p><strong>Conclusion: </strong>The RDPEF is a timely tool for enhancing PE in orphan drug research. By addressing engagement barriers, reducing stigma, and centering patient experience, the framework offers a roadmap for patients, researchers, healthcare providers, and policymakers to create a more inclusive and responsive system for RD patients in Canada.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251404519"},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}