Unleashing the potential of AAV gene therapy

Biopharma Dealmakers (Biopharm Deal). 18/7/2022.

Voyager Therapeutics is unlocking the potential of adeno-associated virus gene therapy to treat a range of neurological disorders, broadening the therapeutic window while ensuring efficacy and safety. The company has already secured capsid option and license agreements with Novartis and Pfizer for target-specific use with CNS and cardiac muscle targets. Voyager also has an ongoing collaboration with Neurocrine Biosciences on a preclinical Friedreich’s ataxia (FA) program and two undisclosed discovery programs in which the company’s novel capsids may be deployed.

SCouT: Synthetic Counterfactuals via Spatiotemporal Transformers for Actionable Healthcare

Bhishma Dedhia, Roshini Balasubramanian, Niraj K. Jha; arXiv:2207.04208v1 [cs.AI] for this version); doi:10.48550/arXiv.2207.04208 (Computer Science > Artificial Intelligence)

We also generate actionable healthcare insights at the population and patient levels by simulating a state-wide public health policy to evaluate its effectiveness, an in silico trial for asthma medications to support randomized controlled trials, and a medical intervention for patients with Friedreich's ataxia to improve clinical decision-making and promote personalized therapy.

We simulate synthetic counterfactuals under a Calcitriol supplement intervention for a Friedreich’s ataxia (FA) patient.

Cardiovascular Research in Friedreich Ataxia

R. Mark Payne; J Am Coll Cardiol Basic Trans Science. null2022, 0 (0); doi:10.1016/j.jacbts.2022.04.005

Patients can develop a cardiomyopathy associated with heart failure and death. • A single gene defect decreases expression of FXN and may be amenable to therapy. • A need exists for greater basic and clinical investigations to advance therapies.

Cerebrospinal Fluid Proteomics in Friedreich Ataxia Reveals Markers of Neurodegeneration and Neuroinflammation

Imbault, Virginie; Dionisi, Chiara; Naeije, Gilles; Communi, David; Pandolfo, Massimo (2022). Frontiers. Collection. doi:10.3389/fnins.2022.885313 

This study supports the hypothesis that the quantitative analysis CSF proteins may provide robust biomarkers for clinical trials as well as shed light on pathogenic mechanisms. Interestingly, DEPs in FA patients CSF point to neurodegeneration and neuroinflammation processes that may respond to treatment.

EE146 Cost and Resource Utilization in Friedreich Ataxia: A Systematic Literature Review

R Zhang, K Buesch; Value in Health, Volume 25, Issue 7, Supplement, 2022, Page S363, doi:10.1016/j.jval.2022.04.396. 

The search retrieved 57 studies, of which 5 fulfilled the eligibility criteria. Among these, 2 reported resource utilization, and 5 reported cost data. No economic evaluation was identified. Neurologists and cardiologists were the most frequently visited physicians, seen by 61-86% and 57-86% of FA patients, respectively. About 23-46% of FA patients were hospitalized for an average of 5-9 days per year. Mean annual direct medical and non-medical cost per patient ranged from £8.893 in the UK to...

CO49 Clinical Efficacy and Safety of Therapeutic Interventions Used in Friedreich Ataxia: A Systematic Review

P Jain, L Badgujar, JA Spoorendonk, K Buesch; Value in Health, Volume 25, Issue 7, Supplement, 2022, Pages S312-S313, doi:10.1016/j.jval.2022.04.147. 

 In total, 32 relevant publications were identified, of which 24 were randomized controlled trials. These publications investigated idebenone (n=11), recombinant erythropoietin (n=6), omaveloxolone (n=3), amantadine hydrochloride (n=2), and A0001, CoQ10, creatine, deferiprone, interferon-γ-1b, L-cartinine levorotatory form of 5-hydroxytryptophan, luvadaxistat, resveratrol, RT001, vatiquinone (all n=1). Age of study participants ranged from 8 to 73 years and disease duration ranged from 4 to 19.

Natural History of Friedreich's Ataxia: Heterogeneity of Neurological Progression and Consequences for Clinical Trial Design

Christian Rummey, Louise A Corben, Martin Delatycki, George Wilmot, Sub H Subramony, Manuela Corti, Khalaf Bushara, Antoine Duquette, Christopher Gomez, J Chad Hoyle, Richard Roxburgh, Lauren Seeberger, Grace Yoon, Katherine Mathews, Theresa Zesiewicz, Susan Perlman, David R Lynch; Neurology Jul 2022, 10.1212/WNL.0000000000200913; DOI: 10.1212/WNL.0000000000200913

Understanding of the diversity within Friedreich's ataxia populations and their patterns of functional decline provides an essential foundation for future clinical trial design including patient selection and facilitates the interpretation of the clinical relevance of progression detected in Friedreich's ataxia.

Rare motor disorder: International study investigates living situation of people with Friedreich’s Ataxia

AAAS and EurekAlert. NEWS RELEASE 11-JUL-2022 DZNE - GERMAN CENTER FOR NEURODEGENERATIVE DISEASES 

The study aims to investigate and evaluate the health-related, psychosocial and economic impacts of the disease. The results of the interdisciplinary project, which combines clinical expertise with expertise in health economics, health care research and psychosocial research, are intended to provide a basis for improving treatment, care and support. In this project, the DZNE works closely with international partners from France (Paris Brain Institute) and Canada (McMaster University) as well as with the healthtech company Aparito and various European university hospitals. "PROFA" is being carried out in six study centers in Europe. It is planned that more than 200 patients aged 12 years and older will participate in the study.

셀리버리 “올해 코로나19·아토피 2상 진입 기대…무증 적절”

[KBIC 2022] 조대웅 대표 발표 

프리드리히 운동실조증(FRDA) 치료제 ‘AAV-FXN-aMTD‘는 TSDT를 적용한 세포·조직투과성 aMTD-융합 Frataxin(FXN) 재조합단백질이다. 조 대표는 “현재 다케다 제약과 공동 연구개발을 진행하고 있다”며 “3단계 마일스톤 효능평가를 미국에서 진행하고 있으며, 기술이전 협의도 동시에 진행 중”이라고 했다.

HTA decision-making for drugs for rare diseases: comparison of processes across countries

Tania Stafinski, Judith Glennie, Andrea Young & Devidas Menon; Orphanet J Rare Dis 17, 258 (2022). doi:10.1186/s13023-022-02397-4 

There is no “magic bullet” solution to address the challenges inherent in the HTA evaluation and reimbursement of DRDs. A variety of approaches are being used by different jurisdictions to address the evaluation of DRDs, in additional to various mechanisms for enabling reimbursement and patient access. As reimbursement and pricing processes for DRDs are being revisited in Canada, the insights gleaned related to stakeholder engagement, the collection of robust real-world data to support innovative reimbursement schemes, and the role that different financing models could play in efforts to achieve equitable access should be considered.