Edition of 10 October 2018

The 13th eHealth Network meeting was held on 15 May 2018 in Brussels. 27 Member States representatives were present, with Norway as an  observer. Ten points were discussed, including:

• European strategies and activities in digital health;
• Interoperability and standardisation;
• Patient access to health data;
• Review and next steps for the launch of the eHealth Digital Service Infrastructure;
• European Reference Networks (ERNs);
• Electronic identification for the exchange of health data;
• National Strategies.

During the agenda point on European Reference Networks, the successes of the ERNs in their first year of existence were discussed. The launch of the Clinical Patient Management System (CPMS) took place in November 2017. The IT platform is provided by the Commission and allows ERN members to create virtual panels to discuss complex patient cases and provide the best advice in terms of diagnosis and treatments. So far, 111 virtual panels have been opened, 13 of which have been closed.

As well as the work in progress:

• The Coordinating group created in March 2017 develops common strategies, guidelines and procedures in areas such as research, knowledge production, surveillance, conflict of interest and data sharing.
• The 24 networks consolidate their governance and work mechanisms
• In cooperation with the ERNs, the Commission is also developing a communication and awareness strategy. Sharing the knowledge generated by ERNs with the community of health professionals and patients is a key goal of the ERN system, and clinical and technical deliverables will be made available to patients and health professionals through a number of tools such as: the Europa site, the ERN web pages and other means of communication.
  

And the obstacles that remain. Currently, the main challenge for ERNs is their integration into national health care systems, including:

• The assessment of the required changes in the political and legal frameworks of each Member State
• Ensuring the harmonious integration of ERNs into the national health system
• Developing patient pathways and decide how a patient case is referred to an ERN
• Defining how Member States will support the functioning of ERNs, including funding the activities of Coordinators and members
  

The Commission is active at the technical, strategic and policy level with the national health authorities in order to accelerate this integration process.

The European Union (EU) Task Force set up by the European Medicines Agency (EMA) and the Heads of Medicines Agency (HMA) on the availability of authorised medicines for human and veterinary use published its 2019/20 work programme at the end of August.
The Task Force will develop and coordinate actions to improve prevention, identification, management and communication on issues that may affect the availability of medicines, in order to improve the continuity of the supply of human and veterinary medicines in Europe. This unavailability of medication can be caused by a lack of authorisation of the products, withdrawal from the market or disturbance in the supply chain.

Thus, it is the mission of the Task Force to:

• Seek ways to minimise supply disruptions and avoid shortages by facilitating the approval and marketing of medicines using the existing regulatory framework;
• Develop strategies to improve the prevention and management of shortages caused by supply chain disruptions;
• Encourage industry best practices to prevent shortages;
• Improve the sharing of information and practices between EU regulatory authorities to better coordinate actions within the EU;
• Encourage collaboration with stakeholders and improve communication of supply problems to EU citizens.

The Task Force will organise a multi-stakeholder workshop on 8 and 9 November 2018 to gather the views of relevant stakeholders, including patients, consumers, health professionals, industry, distributors, universities and regulators.

The withdrawal of the UK from the EU is also likely to affect the availability of medicines in the EU. In this context, the Task Force provides a platform to facilitate and coordinate actions between Member States, the EMA and the European Commission.

On 29 March 2017, the United Kingdom notified its intention to withdraw from the European Union in accordance with Article 50 of the Treaty. The United Kingdom will then become a "third country".

Given the considerable uncertainties, particularly with regard to the content of any withdrawal agreement, sponsors (academic researchers and pharmaceutical companies) leading or planning to conduct clinical trials, and researchers and others involved in the preparation and the conduct of clinical trials, are recalled in a document published by the European Commission of the legal repercussions that will have to be taken into account when the United Kingdom becomes a third country.

Three points are addressed the supply of products, establishment requirements for sponsors and legal representative, and submitting information on clinical trials.

Starting on 1 October, the Directorate General for Health and Food Safety (DG Health) of the European Commission will be chaired by Anne Bucher. She will replace Xavier Prats Monné. The mission of the Health DG is to draw up and implement the Commission's policy on food safety and public health.

Authors of a study published in International Journal of Environmental Research and Public Health achieved the first nationwide population-based study aimed to analyse population-based mortality attributed to rare congenital anomalies to assess the associated time trends and geographical differences in Spain. Data were sourced using databases kept by the National Statistics Institute of Spain, and only rare diseases were included in the study, using the ICD-10. Geographical analysis showed a higher risk of rare congenital anomaly related mortality in the south of the country, and the analysis also showed a decline in age-adjusted mortality rates for congenital anomalies. The authors argue that the study can be used as evidence to be taken into account by health authorities, in order to identify possible risk factors, adopt appropriate preventive measures, and implement health policies and healthcare plans ensuring quality and equity.

The National Organization for Rare Diseases (NORD) used a portion of a multi-year grant award from Shire to develop ten registries to capture high-quality, longitudinal, natural history data systematically collected in order to advance the understanding of diseases and how they are expressed over time.

The data collected is uniform and includes but is not limited to:

• Socio-demographics
• Medical and diagnostics
• Treatment and disease progression
• Management of care
• Quality of life

TREAT-NMD and the Marigold Foundation held a workshop in 2009 to agree on a minimal dataset for patient registries in myotonic dystrophy. Collectively, these registries contain information on over 10,000 myotonic dystrophy patients worldwide (Europe, North America, Asia and Oceania). The survey of the 22 registries, eight years after this workshop, was recently published in Orphanet Journal of Rare Diseases. Authors concluded that the community should consider how to maximise this collective resource in future therapeutic programmes.

Over the past two decades, there has been an increasing attention on rare diseases and managing these diseases. France, the United Kingdom and the United States are viewed as pioneers in terms of developing an infrastructure for rare diseases. However, different organisations deal differently with data management for rare diseases. A systematic review published in Intractable & Rare Diseases Research aims to identify architecture of the system from a data perspective. The authors conclude that developing an integrated information system considering data architecture is crucial. This means identifying data sources, defining datasets and data elements, and defining interactions between data sources. An integrated rare disease information system would in turn facilitate data sharing at a regional, national and even transnational level.

In July 2018, Health and Human Services Secretary Alex Azar approved the recommendation that newborn screening for spinal muscular atrophy (SMA) be implemented nationwide. Thus, SMA becomes part of the Recommended Uniform Screening Panel (RUSP), a list of 35 core conditions that all newborns born in the US are recommended to be screened for.

PerkinElmer developed a new diagnostic tool, available in the US, that can screen for up to six lysosomal storage disorders in newborns:

• Fabry disease
• Gaucher disease
• Niemann-Pick A/B disease
• Pompe disease
• Krabbe disease
• Mucopolysaccharidosis type 1

The new diagnostic kit uses tandem mass spectrometry to measure the activity of alpha-galactosidase A, among other enzymes, in dried blood spots.

The Recommended Uniform Screening Panel (RUSP) is a list of disorders that are recommended by the Secretary of the Department of Health and Human Services (HHS) of the United States, for states to screen as part of their state universal newborn screening (NBS) programs. A team at California Department of Public Health evaluated the follow-up status and demographic characteristics described for 426 newborns diagnosed with one of the 20 primary metabolic disorders on the RUSP between 2005 and 2009. The results were published in Genetics in Medicine and indicated that 55.2% stayed in active care, 20.4% became lost to follow-up, 8.7% moved out of state, 6.3% were determined to require no follow-up, 4.7% refused follow-up and 4.7% died.

Cablivi (caplacizumab) is a medicine used for treating adults who have an episode of acquired thrombotic thrombocytopenic purpura (aTTP). Cablivi is used together with plasma exchange and treatments to reduce the activity of the immune system.

Cablivi was designated an ‘orphan medicine’ on 30 April 2009.

• Marketing authorisation holder: Ablynx NV
• Marketing authorisation date: 31/08/2018

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Mepsevii (vestronidase alfa) is a medicine to treat mucopolysaccharidosis type VII (MPS VII, also known as Sly syndrome), an inherited disease caused by a lack of an enzyme needed to break down complex carbohydrates known as glycosaminoglycans (GAGs).

The disease leads to build up of GAGs in the body, which causes a wide range of problems, including joint stiffness, short stature, enlarged liver and spleen, hearing loss, cataract and delays in development.

Mepsevii was designated an ‘orphan medicine’ on 21 March 2012.

Mepsevii received a marketing authorisation under exceptional circumstances valid throughout the EU on 23 August 2018.

• Marketing authorisation holder: Ultragenyx Germany GmbH
• Marketing authorisation date: 23/08/2018

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Yescarta (axicabtagene ciloleucel) is a medicine for treating two types of blood cancer:

• diffuse large B-cell lymphoma (DLBCL);
• primary mediastinal large B-cell lymphoma (PMBCL).

Yescarta is for adult patients whose blood cancer has returned or has stopped responding to previous treatment.

Yescarta is a type of advanced therapy medicine called a ‘gene therapy product’. This is a type of medicine that works by delivering genes into the body.

Yescarta was designated an ‘orphan medicine’ for DLBCL on 16 Decembre 2014 and for PMBCL on 9 Octobre 2015.

• Marketing authorisation holder: Kite Pharma EU B.V.
• Marketing authorisation date: 23/08/2018

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Myalepta (metreleptin) is a medicine used in addition to diet to treat lipodystrophy, where patients have loss of fatty tissue under the skin and build-up of fat elsewhere in the body such as in the liver and muscles. The medicine is used in:

• adults and children above the age of 2 years with generalised (throughout the body) lipodystrophy (Berardinelli-Seip syndrome and Lawrence syndrome);
• adults and children above the age of 12 years with partial (localised) lipodystrophy (including Barraquer-Simons syndrome), when standard treatments have failed.

Myalepta contains the active substance metreleptin.

Myalepta was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 17 July 2012.

Since Myalepta has been authorised under exceptional circumstances, the company that markets Myalepta will set-up a registry of patients treated the medicine, and conduct studies to further investigate the benefits and risks of treatment including the possibility for Myalepta to trigger the production of antibodies.

• Marketing authorisation holder: Aegerion Pharmaceuticals B.V.
• Marketing authorisation date: 30/07/2018

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Tegsedi (inotersen sodium) is a medicine used to treat nerve damage caused by hereditary transthyretin amyloidosis (hATTR), a disease in which proteins called amyloids build up in tissues around the body including around the nerves.

Tegsedi is used in adult patients in the first two stages of the nerve damage (stage 1, when the patient is able to walk unaided, and stage 2, when the patient can still walk but needs help).

Tegsedi was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 26 March 2014.

• Marketing authorisation holder: Ionis USA Ltd
• Marketing authorisation date: 06/07/2018

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The Journal of Applied Pharmaceutical Science published a review highlighting the drug repositioning as an approach that seeks different therapeutic applications for already approved drugs. It is especially important in the research and development of new orphan medicines since the low number of individuals affected by rare diseases and their large geographic distribution make clinical trials difficult to implement. Thus, drug repositioning is an interesting strategy for rare diseases, given safety profiles, bioavailability, tolerance in humans and some pharmaceutical aspects already known for these approved drugs. This approach could also lower the costs for rare disease patients.

A viewpoint published in JAMA Oncology describes the achievement of the Orphan Drug Act and briefly describes how policymakers would need to look critically at how to modernise the Orphan Drug Act to maintain its relevance in the era of precision oncology without impeding patient access to novel therapies. For example, authors postulate that providing a dedicated pathway for oncology product approval would dramatically reduce the queue of products seeking orphan designation.