Drivers of managed entry agreements to reduce reimbursement challenges of orphan medicinal products: the development of a matrix

Callenbach, M.H.E., van den Berg, S., Hulsbosch, A. et al. Drivers of managed entry agreements to reduce reimbursement challenges of orphan medicinal products: the development of a matrix. Orphanet J Rare Dis 20, 540 (2025). doi:10.1186/s13023-025-04020-8 

"New orphan medicinal products (OMPs) are increasingly expensive and approved with limited clinical evidence". 

The matrix provides a systematic approach applied to mitigate clinical and cost-effectiveness uncertainties and/or reimbursement challenges specific to OMPs through advising MEAs. This study highlights the diversity in the drivers of MEAs to reduce risk and reimbursement challenges specific to OMPs and underscores the relevance of considering both established and innovative MEAs to address these.

Positron emission tomography reveals increased myocardial glucose uptake in a subset of Friedreich ataxia patients

Payne, R.M., O’Connell, T.M., Pride, P.M. et al. Positron emission tomography reveals increased myocardial glucose uptake in a subset of Friedreich ataxia patients. Sci Rep 15, 37247 (2025). https://doi.org/10.1038/s41598-025-21330-w 

 In this cohort of FRDA patients, a PET scan identified two metabolically distinct subclasses of FRDA cardiomyopathy. FRDA patients with severe LVH had greater FDG uptake relative to palmitate utilization than FRDA patients without severe LVH. FRDA patients with severe LVH have systolic and diastolic dysfunction, as well as ongoing cardiac damage as indicated by cTnI leak. These findings suggest that FRDA patients with significant LVH may be at increased risk of complications from surgery or major illness.

Development of an AAV-Based Gene Therapy for the Ocular Phenotype of Friedreich’s Ataxia

Tang H, Gupte S, Xu E, Calabro KR, Friend H, Crosson SM, Fajardo D,Kostamo Z, Zhang H, Peterson JJ, Lin F, Kozmik Z, Lutz CM, Boye SL, Boye SE, Development of an AAV-Based Gene Therapy for the Ocular Phenotype of Friedreich’s Ataxia, Molecular Therapy (2025), doi:10.1016/j.ymthe.2025.10.048.

Gene supplementation via intravitreal injection of a novel AAV2-based capsid carrying FXN partially preserved retinal structure and/or function in both models, establishing proof-of-concept for this therapeutic strategy.

Neuropsychiatric challenges of Friedreich ataxia in a patient residing in a long-term care facility

Wong J, Kwok J, Kim K. Neuropsychiatric challenges of Friedreich ataxia in a patient residing in a long-term care facility. Prim Care Companion CNS Disord 2025;27(5):25cr03965. doi:10.4088/PCC.25cr03965 

 The neuropsychiatric manifestations of FA are often under-recognized despite their significant impact on patient care and quality of life. This case underscores the necessity for comprehensive management strategies that address both the neurological and behavioral aspects of FA. This patient residing in a long-term care facility exhibited chronic depression and significant behavioral challenges including refusal of food, medications, and nursing care, alongside physical aggression. Despite initial treatment with citalopram, behavioral symptoms persisted while the neurovegetative signs of depression improved. As the escalation of the patient’s behavioral symptoms marked a critical turning point, divalproex ER was introduced and titrated to manage his mood instability. Subsequently, the patient’s mood and behavior symptoms noticeably improved without worsening motor dysfunction, highlighting the importance of personalized psychopharmacologic interventions.

Jupiter Neurosciences, Inc. strategic partnership with Zina Biopharmaceutica

October 22, 2025. The company develops JNS101, which is in Phase II trial for the treatment of Friedreich's Ataxia, a rare inherited disease that causes damage to the nervous system, as well as mobility dysfunctions; and JNS108 that is in Phase II trial for treating mild cognitive impairment/early Alzheimer’s disease. It is also involved in the development of JNS102, which is in Phase II trial for the treatment of mucopolysaccharidosis type 1; and JNS107 that is in Phase II trial for treating mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome. In addition, the company develops JNS115, which is in Phase IIa trial for the treatment of Parkinson’s disease. It has a strategic partnership with Zina Biopharmaceuticals, LLC to advance Phase 2a clinical trial to evaluate the safety, tolerability, and pharmacokinetics of Resveratrol (JOTROLTM) in individuals with Parkinson’s disease; and with Aquanova AG to develop a series of consumer-focused nutritional products targeting longevity, aging, and healthspan. The company was formerly known as Jupiter Orphan Therapeutics, Inc. and changed its name to Jupiter Neurosciences, Inc. in August 2021. Jupiter Neurosciences, Inc. was incorporated in 2016 and is headquartered in Jupiter, Florida.

Exploring the pleiotropic effects of lncRNA in different repeat expansion disorders

Soumalya Das, Shubhi Khandelwal, Sakshi Shukla, Amit Kumar, Exploring the pleiotropic effects of lncRNA in different repeat expansion disorders, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2025, 168089, ISSN 0925-4439, doi:10.1016/j.bbadis.2025.168089.

A Probabilistic Deep Ensemble Framework for the Objective Assessment of Friedreich Ataxia

Maneesha Randeniya, Kanishka Ranaweera, Thang Ngo, et al. A Probabilistic Deep Ensemble Framework for the Objective Assessment of Friedreich Ataxia. TechRxiv. October 16, 2025. DOI: 10.36227/techrxiv.176062677.75204670/v1

There was strong agreement between the proposed ensemble and clinical mFARS scores, reflected in a Pearson correlation of 0.81, Spearman's correlation of 0.76, R² of 0.46, RMSE of 10.30, and MAE of 8.79 on the unseen test set. Uncertainty was systematically evaluated using Uncertainty Characteristics Curves (UCC), where the ensemble achieved an Area Under UCC (AUUCC) of 8.83.

Chapter 23 - Omaveloxolone: a nuclear factor erythroid 2-related factor 2 activator for Friedreich’s ataxia

Ziquan Zhao, Junjie Wang, Mengchen Lu, Qidong You, Zhengyu Jiang, Chapter 23 - Omaveloxolone: a nuclear factor erythroid 2-related factor 2 activator for Friedreich’s ataxia, Editor(s): Bin Yu, Peng Zhan, Drug Discovery Stories, Volume 2, Elsevier, 2026, Pages 331-344, ISBN 9780443338854, doi:10.1016/B978-0-443-33885-4.00038-X. 

 Nuclear factor erythroid 2-related factor 2 (NRF2) is an important cytoprotective transcription factor that affects the fate of the cell. Impairment of the NRF2 signaling pathway has been regarded as a major contributor to the pathophysiology of FRDA, and targeting NRF2 activation has become an attractive strategy for the treatment of FRDA.

Targeting rare splicing defects: Antisense oligonucleotides offer a therapeutic strategy in FRDA

Targeting rare splicing defects: Antisense oligonucleotides offer a therapeutic strategy in FRDA, Kerkhof, Laurie M.C. et al., Molecular Therapy Nucleic Acids, Volume 36, Issue 4, 102723 doi:10.1016/j.omtn.2025.102723

Using patient-derived cells, the authors demonstrated that antisense oligonucleotides (ASOs) targeting splicing regulatory elements effectively restore splicing deficits and increase frataxin expression. While encouraging in cell-based studies, this strategy is limited to a small subset of individuals with FRDA carrying these rare mutations and requires functional validation in disease-relevant tissues.

Analysis of a Modified Version of the Inventory of Non-Ataxia Signs Over 12 Years in Patients with Friedreich's Ataxia in the EFACTS Study

Lischewski, S.A., Dogan, I., Giunti, P., Parkinson, M.H., Mariotti, C., Durr, A., Ewenczyk, C., Boesch, S., Nachbauer, W., Klopstock, T., Stendel, C., de Rivera Garrido, F.J.R., Schöls, L., Fleszar, Z., Klockgether, T., Grobe-Einsler, M., Giordano, I., Rai, M., Pandolfo, M., Jacobi, H., Hilgers, R.-D., Schulz, J.B., Reetz, K. and the EFACTS Study Group (2025), Analysis of a Modified Version of the Inventory of Non-Ataxia Signs Over 12 Years in Patients with Friedreich's Ataxia in the EFACTS Study. Mov Disord. doi:10.1002/mds.70084

Participants were drawn from the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). The modified INAS count (presence/absence, 0–16 scale) and modified INAS sum (severity-weighted, 0–84 scale) were evaluated using linear mixed-models and standardized response means (SRMs). Items rare (<5%) and uncharacteristic in Friedreich's ataxia were excluded (chorea, myoclonus, fasciculations, resting tremor, rigidity)