The definition of neuronopathic Gaucher disease.

Neuronopathic Gaucher disease (nGD) has a very wide clinical and genotypic spectrum. However, there is no consensus definition of nGD, including no description of how best to diagnostically separate the acute form-Gaucher type 2-from the subacute or chronic form-Gaucher type 3. In this article, we define the various forms of Gaucher disease with particular emphasis on the presence of gaze palsy in all patients with nGD. This consensus definition will help in both clinical diagnosis and appropriate patient recruitment to upcoming clinical trials.

Orphan drug development and the impact on non-medical support groups.

The Orphan Drug legislation in the United States and later in the EU has had a significant impact on patients worldwide who suffer from an orphan condition. Apart from providing statutory encouragement and incentives to pharmaceutical companies to develop therapeutic products it has resulted in the encouragement of patients to come together to form patient bodies to advocate on behalf of patients. Starting in a modest way patient groups have gained experience in working with clinicians and scientists and representing their members to companies and to healthcare providers in national European and global environments. This article describes the history and evolution of the patient body and the coming together of national patient groups through umbrella organisations which have proven to be a powerful advocate for pan European and global collaboration and humanitarian aid. It also will review of some unintended consequences of the legislation.

Understanding patient and parent/caregiver perceptions on gene therapy in Gaucher disease: an international survey.

BACKGROUND: Gaucher disease is a rare, autosomal recessive genetic disorder. It is caused by a lack of sufficient activity of the lysosomal enzyme known as glucocerebrosidase, which leads to an accumulation of glucocerebroside, a fatty substance, in the spleen, liver, bone marrow, and rarely, the lungs or central nervous system. While there are several treatments available for people with Type 1 Gaucher disease and the visceral aspects of Type 3 Gaucher disease, no cure is present for any type of Gaucher disease. Clinical trials are currently underway to investigate the safety and efficacy of gene therapy in Gaucher disease, which has the potential to become a new type of (curative) treatment in the future. Gene therapy is a relatively new therapeutic approach, and with the desire to keep the community informed about new treatment developments, the International Gaucher Alliance (IGA) set-up a Gaucher disease specific survey to gauge current perceptions. The survey aimed to benchmark understanding of, and the educational needs surrounding, gene therapy among the Gaucher disease community. BODY: An international, online survey was developed, comprising twelve questions ranging from multiple choice, Likert scale, single tick-box, ranking and open questions. The survey was developed following three patient and caregiver focus groups and underwent review from members of the IGA for readability and accuracy before going live to respondents. The survey was available for two months and shared to audiences via specific Gaucher community channels. CONCLUSION: Over 100 patients and parents/caregivers from the Gaucher disease community completed the survey, including people living with Type 1 Gaucher disease (52.88%), people living with Type 3 Gaucher disease (3.85%), parents/caregivers of people living with Type 1, 2 or 3 Gaucher disease (39.42%), and other (3.85%) who were defined as parents of multiple people with Gaucher disease. The survey uncovered various commonalities in perception of gene therapy among all groups, with large knowledge gaps identified on the mode of action, the usefulness of gene therapy and overall understanding of the therapeutic area. This survey provides an overview of the type of information that could be valuable to the Gaucher disease community when developing educational materials.

A global neuronopathic gaucher disease registry (GARDIAN): a patient-led initiative.

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder. GD types 2 and 3 are known as neuronopathic Gaucher disease (nGD) because they have brain involvement that progresses over time. Implementing a systematic approach to the collection of real-world clinical and patient-relevant outcomes data in nGD presents an opportunity to fill critical knowledge gaps and ultimately help healthcare providers in the management of this patient population. This paper summarizes the development of a patient-initiated Gaucher Registry for Development Innovation and Analysis of Neuronopathic Disease (GARDIAN). METHODS: The International Gaucher Alliance led the GARDIAN planning, including governance, scope, stakeholder involvement, platform, and reporting. Registry element input was determined in a series of meetings with clinical experts, patients, and caregivers, who identified key clinical variables and the draft content of nGD patient-reported outcomes (PRO) and observer-reported outcomes (ObsRO) focusing on symptoms, patient physical and emotional functioning. These were then tested in cognitive interviews with patients with nGD (> 12 years of age) and caregivers. RESULTS: Core registry data elements (n = 138) were identified by seven global clinical experts from Egypt, Germany, Israel, Japan, United Kingdom (UK), and United State (US) and reviewed via online Delphi method by 14 additional clinicians with experience of nGD from six countries and three pharmaceutical representatives. The elements were consistent with those identified via interviews with 10 patients/caregivers with nGD from Japan, Sweden, UK, and US. Key domains identified were demographics, diagnostic information, health status, clinical symptomatology, laboratory testing, treatment, healthcare resource utilization, aids/home improvements, and patient/caregiver burden and quality of life, specifically physical functioning, self-care, daily and social activities, emotional impacts, support services, and caregiver-specific impacts. Nine caregivers and six patients from the US, UK, China, Mexico, Egypt, and Japan participated in the cognitive interviews that informed revisions to ensure that all items are understandable and interpreted as intended. CONCLUSIONS: The comprehensive set of clinical and patient relevant outcomes data, developed collaboratively among all stakeholders, to be reported using GARDIAN will bridge the many gaps in the understanding of nGD and align with regulatory frameworks on real-world data needs.

A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide.

BACKGROUND: Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifestations and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs. METHODS: The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of benefit, in selected countries, through donation of ERT to nonprofit organizations, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company. RESULTS: As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year. CONCLUSIONS: The response rate for follow-up data at 1 year was high, with data collected for > 90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These findings suggest that the program can benefit selected patients previously unable to access disease-specific treatments. Further innovative solutions and efforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world.

Force majeure: therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease.

Gaucher disease is the first lysosomal disorder for which clinically effective enzyme replacement therapy has been introduced. Lifelong treatment with imiglucerase, the recombinant glucocerebrosidase manufactured by the Genzyme Corporation (MA, USA), is administered intravenously - usually at biweekly intervals. An acute shortage of imiglucerase (to 20% of prior global supply) has occurred as a result of viral contamination of the production facility; production was halted, and a full supply of imiglucerase is not anticipated until January 2010. An urgent meeting of physicians, researchers, and patients was convened through the agency of the European Working Group for Gaucher Disease; this was instigated by patients internationally represented by the European Gaucher Alliance. Here we present a position statement based on the findings of the group, with key recommendations about identification and monitoring of at-risk patients threatened by the abrupt withdrawal of treatment, the equitable distribution of residual imiglucerase - and access to alternative treatments including those that have completed phase III clinical trials but have not yet been licensed.

Measuring disease activity and patient experience remotely using wearable technology and a mobile phone app: outcomes from a pilot study in Gaucher disease.

BACKGROUND: Gaucher disease is an inherited lysosomal storage disorder of which there are three subtypes. Type 1 disease has no neurological involvement and is treatable with enzyme replacement therapy. Type 2 disease results in infant death and type 3 disease is a heterogenous disorder characterised by progressive neurological decline throughout childhood and adult life. Endeavours to find a therapy to modify neurological disease are limited by a lack of meaningful clinical outcome measures which are acceptable to patients. RESULTS: We present results from a pilot study utilising wearable technology to monitor physical activity as a surrogate of disease activity/severity paired with a mobile phone app allowing patients to complete self-reported outcome measures in the real world as opposed to the hospital environment. We demonstrate feasibility of the approach and highlight areas for development with this study of 21 patients, both children and adults. CONCLUSIONS: We illustrate, where patients engage in the methodology, a rich dataset is obtainable and useful for proactive clinical care and for clinical trial outcome development.

The European Gaucher Alliance: a survey of member patient organisations' activities, healthcare environments and concerns.

BACKGROUND: The European Gaucher Alliance (EGA) was established in 1994 and constituted in 2008 as an umbrella group supporting patient organisations for Gaucher disease. Every two years, the EGA conducts a questionnaire survey of member associations to help develop its priorities and annual work programme. Results of the latest survey are presented. METHODS: Between June 2012 and April 2013, the 36 members and associate members of the EGA were asked to complete a questionnaire detailing membership numbers, disease specific treatments used by patients, means of access to treatment, availability of treatment centres and home infusions, sources of support for patients with Gaucher disease, patient organisations' activities, collaborations, funding sources and any issues of concern. Questionnaires completed in 2012 were revised in January 2013 and responses analysed between July and September 2013. RESULTS: Thirty three members returned data on one or more questions. Findings identified inequalities in access to treatment both within and between members' countries. Three of 27 countries, for which data were available, relied totally on humanitarian aid for treatment and 6% of untreated patients in 20 countries were untreated because of funding issues, a situation many feared would worsen with deteriorating economic climates. Access to treatment and reimbursement represented 45% of members' concerns, while 35% related to access to specialist treatment centres, home infusions and doctors with expertise in Gaucher disease. Member associations' main activities centred on patient support (59% of responses) and raising awareness of Gaucher disease and patients' needs amongst the medical community, government and healthcare decision makers and the general public (34% of responses). Twenty one (78% of respondents) indicated they were the only source of help for Gaucher disease patients in their country. For many, activities were constrained by funds; two members had no external funding source. Activities were maximised through collaboration with other patient organisations and umbrella organisations for rare diseases. CONCLUSION: The survey provided a 'snapshot' of the situation for patients and families affected by Gaucher disease, helping the EGA direct its activities into areas of greatest need.