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Edition of 26 June 2020

International News

Rare cancers in India, a completely forgotten medical area

In India, rare cancers have a long list of unmet services, including the absence of a definition of rare cancers in the country, the non-availability of data (considered to be the top issue for the domain), the lack of access to the healthcare systems by the local population, and the unavailability of access the few rare cancers drugs available outside India.

The authors recommended a nationwide status for rare cancers with concrete steps including establishing clear definition of rare cancers. Priorities include the creation of the legal, administrative and financial conditions to create a legislative framework, the creation of rare cancers registry and access to health facilities for more patients to healthcare services. Experts request awareness raising and research in order to create the conditions for better diagnosis and treatment of rare cancers, as well as the development of drugs. They also recommended that urgent studies be conducted to determine the prevalence of rare cancers in India and current therapeutic approaches, and to involve young Indian researchers in this work.

Rare Genetic Diseases in two Indian low-resource regions, Jammu and Kashmir

Jammu and Kashmir (J&K), two Indian low-resources regions, are reported to have a large number of genetic diseases due to the presence of conglomeration of diverse population groups. J&K’s population is largely practicing consanguinity and is living in a geographic isolation thus creating a unique disease profile. The situation described above remained unknown due to the absence of genetic-based researches in the J&K region. The relationship of this population to genetic diseases, can be developed through genetic research, to thus help to address the question and ultimately design diagnostic protocols, develop therapeutics, and conduct molecular genetic diseases.

The authors suggested methods for successful molecular genetic studies, genetic linkage studies (by associating chromosomal, genomic, with a disease genotype and information on families), and next generation DNA sequencing. On a general note, India also has challenges regarding rare diseases, for example, the absence of RD codification, clinical challenges (lack of appropriate clinical resources and specific literature), significant psycho-socio-economic issues of people with rare diseases following social isolation, imprecise diagnosis, and adequate therapeutic interventions. Public and government involvement is highly desired in terms of legislative policies, research on RDs including genetic diseases, novel therapeutic and strategies, and the development of national RD support websites which will contribute in sharing information with patients and their families.

The use of real-world data in rare disease medicines through health technology in Canada and the UK

A study in Value in Health Journal highlights that in Canada and in the United Kingdom (UK), researchers and decision-makers are calling for the use of real-world data (RWD) in health technology assessments (HTAs) for rare disease medicines. RWD is data collected from a variety of sources and is linked to patient health records.

Western Australia’s rare disease policy framework and Undiagnosed Diseases Program

Western Australia is the first State in Australia to set up a rare disease policy framework and an Undiagnosed Diseases Program (UDP) through which the State deals with undiagnosed cases of people with a rare disease. The UDP comprises an expert panel composed by various experts, and their collaboration will hopefully lead to a diagnosis thus reducing the diagnostic odyssey faced by patients.

James Lind Alliance Priority Setting Partnerships on rare musculoskeletal diseases in adults

An article in the Orphanet Journal of Rare Diseases (OJRD) highlights the work of the James Lind Alliance (JLA), a United Kingdom non-profit organisation which brings together clinicians, patients and their carers, through two surveys, with the purpose of identifying the top 10 research priorities for rare musculoskeletal diseases in adults, such as osteogenesis imperfecta, fibrous dysplasia/McCune-Albright syndrome and X-linked hypophosphatemia. The first survey, identified 39 questions as research priorities on treatment and the long-term management of rare musculoskeletal diseases. The research priorities questions were refined to 25 following the second survey.

Finally, 10 research priorities (among them skeletal symptoms, psychological care, adequate treatment and long-term disease management) were finally selected during the last step, a workshop that gathered patients, carers, and healthcare professionals. Quality research on adequate and long-term management on rare musculoskeletal diseases adults is still rare. JLA researchers called on healthcare experts and all stakeholders to address the top 10 identified priorities in the future

Multi-omic analyses of rare diseases research

An article in the Orphanet Journal of Rare Diseases (OJRD) focuses on a research analysis using English articles on integrative omics and rare diseases from electronic databases (Medline, PubMed, Google Scholar), grey literature databases and the Cancer Genome Atlas publications published prior to 2019. This review of 66 articles, revealed that the content of 66% of the articles are studies of multi-omics and rare cancers, 3% of them on integrative omics and on pre-cancerous conditions, and 33,3% are studies on non-cancerous rare diseases. An increase of multi-omic studies is noted (66.7 conducted since 2016, and 33% since 2018) in the fields of metabolomics, genomics, epigenomics and phenomics.

In their journey, rare diseases patients are facing various challenges (early diagnosis, lack of diagnosis, appropriate treatment), and multi-omics studies will contribute in the increase of the diagnosis rate. Multi-omics research on rare diseases can improve the identification of biomarkers, molecular subtypes, and new therapeutics. Currently, 100,000 Genomes Project, the Five Million Genomes project, the NIH UDP and the IRDiRC are contributing in multi-omics projects, and already constitute a platform. Further collaboration of stakeholders in integrative omics will contribute to robust outcomes and will systematise collection and reporting structures, as multi-omics studies are challenged by a variety of methodological approaches.

European News

Rare disease centres formally designated in Switzerland

In Switzerland, patients living with rare diseases often experience a delay in diagnosis. They often have to consult different medical specialists for an appropriate diagnosis. In order to improve RD and patients’ access to healthcare systems, 6 new centres for rare diseases were created in Switzerland in order to help patients to reduce their diagnostic odyssey. The centres are interdisciplinary and offer a range of medical specialists. The new centres will therefore help RD patients access the care they need.

The centres will also play a role in coordinating activities of clinics, specialised institutes, and public and private hospitals. The centres will also provide information through a hotline, organising postgraduate workshops in hospitals, and taking part in research. On 20 May 2020, the National Coordination for Rare Diseases in Switzerland (Kosek) formally recognised the 6 RD centres. The new centres obtained a certification attesting that they meet quality criteria, and are fully complying with international RD standards.

Press release in German
Press release in French
Press release in Italian

Challenges and propositions to improve patient access to advanced therapeutic medicinal products in Austria

A report on advanced therapy medicinal products (ATMPs) is highlighting the work of RARE IMPACT (an initiative that improves ATMPs in Austria) and its partners (health technology assessment agencies, regulatory bodies, patients groups, clinicians), and their proposals related to transformative rare diseases treatments in Europe, and their work to increase discussions among stakeholders.

In Austria, as well as in France, rare diseases patients access 90% orphan drugs, but there are still challenges in terms of reimbursement for ATMPs in Austria, and the country is working on obstacles to accessing ATMPs. Austria started legislative changes for more assessment conformity and for sustainable access to orphan products, however ATMPs are still not concerned by this legislative move, as ATMPs are classified as in-hospital products, and this does not comply with HTA assessment. ATMP funding will then pass through reformed security funds (health insurance), with the challenge of allocation of funds between treatment centres and hospitals. Although ATMPs for rare diseases are available in the country, access to rare diseases, including ATMPs may be an issue and the government created the National Centre for Coordination of Rare Diseases (NSKE) to improve access to rare diseases products.

European Commission to invest 9.3€ billion in the new EU4Health programme

The European Commission (EC) will invest 9.3€ billion in a new health programme for the period from 2021 to 2027. The EC’s new health program focuses on different health areas, including non-communicable diseases, rare diseases (RD), cancer, and risks from health determinants, post-Covid-19 recovery and crisis preparedness, health inequalities in population groups of the EU, access to adequate and quality care, and health issues regarding environmental degradation and pollution. The EU4Health programme also includes cross-border collaboration, through ERNs, especially on digital and innovative solutions. The ERN for rare, low prevalence and complex diseases will cover be expanded to cover other rare non-communicable as well as infectious diseases.

The EU4health programme has three main objectives: (i) protection of EU populations from cross-border health threats and improve the management of health crisis, (ii) availability of medical devices and medicines, and innovation programmes, and, (iii) to strengthen health care forces and systems (promotion and prevention programmes. The EUHealth programme, in collaboration with Horizon Europe, the EU’s principal research and innovation, will support health sectors such rare diseases, and research.

Italian actors involved in the ERNs hold first meeting for better coordination and integration of the networks in Italian health system

The ERNs Italian community had their first meeting in Pisa, in the framework of the International Day for Rare Diseases. The meeting, which focused on the role of patients, ERNs’ good practices in addressing RD, management of RD and their integration in the health system, was attended by main Italian representatives of ERNs, including ERN ReCONNET, ERN Bond and MetabERN, representatives from the Italian National Institute of Health (ISS) and patients’ representatives involved, the Italian RD National Alliance and representatives from ePAG Italy. The participants expressed a significant leap for ERNs, in terms of the importance of ERNs in the country’s health system, and the wish to make ERNs a reference for the Italian health system. The representatives of the three mentioned ERNs present during the meeting were asked to start discussions with the Ministry of Health in the country and other concerned institutions.

Nominations for 2021 EURORDIS Black Pearl Awards are now open

The nominations for the EURORDIS Black Pearl Awards for 2021 edition are now open till 11 September 2021. The awards recognise those making an exceptional contribution to the rare disease field. The nominations are open for a number of categories, including Scientist Award, Policy Makers, Patients Advocates, and International Media Award.

Participate in an online stakeholder survey on the use and reuse of health data

The European Commission has initiated a study that aims to examine in which manners the processing of personal health data is governed across the European Union (EU) and how this might affect the cross-border exchange of health data in the EU in light of the GDPR. The study is executed by the EUHealthSupport consortium.

As part of this study stakeholders are invited to participate in an online survey, aimed to collect the views of experts and organisations representing the wide range of stakeholders, including patients, care providers, industry, public bodies and researchers. The results of the study will be used to identify possible future actions to be developed at EU level, such as new legislation or codes of conduct for health data sharing for research or policy purposes, also in light of the current COVID-19 pandemic.

In total, the survey will take approximately between 10 and 15 minutes to complete. It will be possible to respond till Sunday 5 July 2020.

Answer the survey

European Brain Council’s two-year study on coordinated care for rare neurological diseases patients

The European Brain Council (EBC) initiated a two-year study, from 2018 to 2021 (following an initial study in 2017) on early diagnosis for rare neurological diseases (RNDs), coordinated and multidisciplinary care. 60% of patients with RNDs are undiagnosed due to severe phenotype and genotype heterogeneity according to the ERN rare neurological diseases (ERN-RND). Patients with RNDs also face unequal access to healthcare systems, care coordination, and appropriate care (access to specialist centres), with particular difficulties for chronic RNDs that require various therapeutic approaches (symptomatic, supportive and surgical). The study then focused on reducing gaps in processes and highlighting missteps (such as increasing healthcare but not necessarily improving patient health outcomes).

The study brings attention to the need for the patient care, consideration of patients’ views, the cost-effectiveness of management care throughout Europe, the role of national policies, including National Rare Diseases plans. The first EBC study (2017) called for earlier intervention and a better management of brain diseases, raised awareness of RNDs. The results of the second round of the study will be published in Mid-2021.

Ithanet, EuroBloodNet’s portal for clinicians and researchers working on haemoglobinopathies

The Ithanet portal is collecting information for clinicians and researchers working on haemoglobinopathies (monogenic diseases) through various databases (IthaGenes), epidemiology (IthaMaps) and HPLC data (IthaChrom), and gene-ranking metric IthaScore. Following the collected information, Ithanet published an article entitled Genetic Modifiers at the Crossroads of Personalised Medicine for Haemoglobinopathies which focuses on IthaScore, and the evidence-based gene ranking metric for haemoglobinopathy-specific phenotypes. IthaScore is an innovative ranking metric for genes and distinctive clinical phenotypes in haemoglobinopathies, knowledge on disease modifiers, and is easily modifiable. IthaScore also concerns analyses, molecular basis of disease, phenotype diversity, and new gene identification.

Rare diseases and coronavirus pandemic in Poland

Following the coronavirus pandemic, health experts are working hard to find a vaccine to treat the Covid-19. In the United Kingdom (UK) and in Poland, RD patients living with lupus (rare autoimmune disease) were directed to a given medicine, such as hydroxychloroquine in Poland, marketed in the name of Arechin, recognised as supplementary drug for SARS-CoV-2 infections, that was used in all Polish hospitals. In Poland, as well as in the UK, lupus patients did not access to Arechin, as all available stock was transfer to hospitals. It was difficult for lupus patients to access the medicine. As of mid-March, the Polish Dermatological Society recommended that patients to look for an alternative as hydroxychloroquine may not be readily available. In April, the Polish Dermatological Society that Arechin and Plaquenil (hydroxychloroquine) will be available in restricted amounts, for patients with lupus and other autoimmune diseases.

Orphan Drugs

Pediatric Orphan Drug Classification from 2010 to 2018

There is a lack of orphan drug data, especially concerning pediatric drugs designated as orphan drugs. An article in Biomedical and life sciences journal literature describes the classification by experts of 402 orphan drug indications approved by the US Food and Drug Administration from 2010 to 2018, and concluded that 33.8% (136) of the 402 orphan drugs were paediatric orphan drugs, and from which 60 (44.1%) were novel drugs, 45 (33.1%) non-novel drugs treating 1 or more common diseases, and 31 (22.8%) non-novel drugs for rare diseases treatment. 97 drugs were eligible for orphan drugs designation, and 20 of them (20.6%) obtained the designation.

The experts noticed a growth of orphan drug development recently, with an increase of paediatric orphan drugs available. The authors highlight substantial unmet for paediatric rare diseases treatment.

Public spending for orphan drugs in western countries and implementation of health technology assessment principles

An article in the European Journal of Clinical Pharmacology indicates that Western countries currently face challenges concerning rare diseases therapies, the obligation to share their public speeding on orphan drugs (OD), and the adaptability of health technology assessment (HTA) and OD assessment and regulation.

On the basis of an extensive literature review (from January 1990 to May 2018) the authors make several observations concerning OD regulations, including high prices applied for OD, and the absence of clarity about incomes from OD distribution outside national borders. They notice differences in western countries regarding fragmented implementation of HTA, and call for harmonisation of regulations at the international level and for a strategy for producers.

Committee for Orphan Medicinal Products meeting report on the review of applications for orphan designation March 2020

The COMP adopted 11 positive opinions recommending the following indications for designation as orphan medicinal products to the European Commission:

• Ovarian cancer,
• Haematopoietic stem cell transplantation,
• Myasthenia gravis,
• Hepatocellular carcinoma,
• Progressive familial intrahepatic cholestasis,
• Haemophilia A,
• Fetal and neonatal alloimmune thrombocytopenia,
• Acute myeloid leukaemia,
• AL amyloidosis
• Insulin autoimmune syndrome,
• Pyruvate kinase deficiency.

Consult the meeting report

Committee for Orphan Medicinal Products meeting report on the review of applications for orphan designation April 2020

The COMP adopted 12 positive opinions recommending the following indications for designation as orphan medicinal products to the European Commission:

• Multiple myeloma,
• Marginal zone lymphoma,
• Retinal detachment,
• Paroxysmal nocturnal haemoglobinuria,
• Hepatocellular carcinoma,
• Canavan disease,
• Soft tissue sarcoma,
• Neonatal encephalopathy
• Non-traumatic aneurysmal subarachnoid haemorrhage,
• Immune thrombocytopenia,
• Amyotrophic lateral sclerosis,
• Duchenne muscular dystrophy.

Consult the meeting report

Meeting highlights from the Committee for Medicinal Products for Human Use 23-26-03 March 2020

EMA’s human medicines committee (CHMP) recommended three medicines at its March 2020 meeting for:

• Zolgensma* (onasemnogene abeparvovec), an advanced therapy medicinal product (ATMP) for the treatment of babies and young children with spinal muscular atrophy, a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement,

• Pretomanid FGK* (pretomanid) received a positive opinion from the CHMP for the treatment of tuberculosis in combination with bedaquiline and linezolid,

• Sarclisa* (isatuximab) for the treatment of multiple myeloma, a cancer of the bone marrow.

Meeting highlights from the Committee for Medicinal Products for Human Use CHMP) 28-30 April 2020

EMA’s human medicines committee (CHMP) recommended two medicines at its April 2020 meeting for:

• Daurismo* (glasdegib) for the treatment of acute myeloid leukaemia, a cancer of a type of immature white blood cell called myeloid cells,
• Reblozyl* (luspatercept) received a positive opinion from the CHMP for the treatment of adults with transfusion-dependent anaemia associated with myelodysplastic syndromes (diseases in which the body produces large numbers of abnormal blood cells) or beta-thalassaemia (a blood disorder that reduces the production of haemoglobin).

Screening and prenatal diagnosis

Successful German national newborn screening for Severe Combined Immunodeficiencies

The newly introduced newborn screening program for Severe Combined Immunodeficiences (SCID) in German has been shown to be successful five months after being introduced in the country. When SCID is treated in the three days following birth, 90% of the affected children do not develop symptoms. The non-treatment of newborns with SCID causes severe infections and even death. The Working Group for Pediatric Immunology (API) was involved in the introduction of SCID newborn screening in Germany.

Joint Call to Action for Newborn Screening for Rare Diseases

A Call to Action in favor of a Newborn Screening for Rare Diseases (NBS for RD) in Europe was jointly made, in December 2019, by three organisations, the International Patient Organisation (IPOPI), the International Society for Neonatal Screening (ISNS), and the European Society for Immunodeficiencies (ESID) at the IPOPI 13th EU PID Forum is available.

There is room for improvement of mechanisms used to implement NBS in EU Member States for example in assessing access to preventive programmes for newborns. There is no central body in charge to centralise data and guide newborn screening practices. The three organisations called EU to: (i) to implement guidelines for RBS for RD, (ii) to set up an EU platform for NBS for RD and an EU NBS for RD standing committee, and (iii) to position EU as the central point in collecting information on RBS for RD best practices and recommendations.

Clinical trial study design

Clinical trial-on-chips impact on rare diseases

Clinical trials-on-chips (CToCs) are able to overcome difficulties encountered in developing medical products for rare diseases. CToCs once well applied, will greatly impact clinical trial studies to assess clinical risk and benefit, and to stratify populations. To better understand the CToCs move in RD therapies development, a working group of experts and patient representatives held discussions around key themes such as data collection, microphysiological systems, CToCs feasibility and risks, and the way to get stakeholders on board. The working group had a debate on including RD without therapies as the target group for initial CToCs tests, or to start those tests with well-defined RD diseases with known clinical outcomes. Re-purposing of approved drugs was mentioned as the solution for first CToCs tests.

CToCs will surely help to access treatment in the case of RD for which it is still difficult to treat. There are also current plans by scientists to expand the CToCs technology using in vitro tools for best therapeutic assessment.

Rare diseases studies using simulations and matching methods

Studies on rare diseases using Monte Carlo simulations and matching methods (Propensity score matching (PSM), Mahalanobis distance matching, mixture of PSM and exact matching) and carried out on small numbers revealed that PSM is performing better that the two other matching methods. Experts recommended using PSM with optimal algorithm and one-five matching ratios in very small samples, and to apply carefully matching algorithms and matching ratio.

A United States Clinical Trial Readiness Program on Spinal muscular atrophy

An article of Orphanet Journal of Rare Diseases (OJRD) focuses on a pilot clinical trial program launched in 2018 by a United States (US) pharmaceutical company, Cure SMA, to meet trial sponsors’ and patient communities’ expectations. The pilot program was set up for new and prospective Spinal muscular atrophy (SMA) clinical sites, with the participation of nine US hospitals. SMA is a rare disease with an evolving treatment context. Cure SMA used surveys to evaluate the pilot program which included the evaluation of the virtual site, the trial readiness toolkit, the program for physical therapists, as well as the clinical evaluation.

Cure SMA expanded the experience to other sites, and was able to define best practices toolkits. Cure Europe was inspired by Cure SMA’ s experience and is planning to carry out similar experiences in the EU countries, in collaboration with Cure SMA. The Clinical Trial Readiness Program on SMA is a new way to support clinical trial with the contribution of patients working besides pharmaceutical groups.

Quality of life

Challenges for children with rare diseases in the education system

An article in Health and Quality of Life Outcomes Journal highlights a study on the challenges faced by children living with rare diseases in the educational system. The outcomes of the study in which children with rare diseases, parents, and schools staff took part stated that the low number and the delay or absence of a diagnosis are the main causes that affect the quality of life of children with rare diseases, and that are challenging both the children and the school staff. Other issues were identified, including knowledge, acceptance, participation, discrimination, or health-related support. Children with rare diseases are therefore rare in the school system. The experts recommended inter-sector and inter-disciplinary health and educational measures for address the issue.

Parents' experience of caring for children with rare neurodevelopmental disorders

An article in International Journal of Qualitative Studies in Health and Well-being reports on parents of children living with rare neurodevelopmental disorders who are struggling medically, socially, and on the behavioural side, to obtain adequate assistance and health care access. This leads to isolation and exclusion due to social taboo and stigma, vulnerability, inadequate health care and social systems, and incomprehension of friends and family members. Medical, social, and family supportive systems and services will help reduce their isolation and exclusion.

Lived experiences and well-being of adults with SMA

An article in the Orphanet Journal of Rare Diseases (OJRD) reports on a study that reviews the odyssey of adults with SMA regarding care pathways, and patient-centered reported outcomes. The study, through ninety-five articles, reviews also research in healthcare and well-being of adults with SMA. Advances in supportive care and therapies were focused on children with SMA. For the adults observed over a period of two years, slow declines were noted, as well as limitations in mobility, physical health deterioration, emotional difficulties, and the absence of social support. These patients need best clinical practice, clinical research, long-term outcomes, and advances in health policy.

Bioinformatics and biotechnology

PRIORI-T: phenotype-driven gene prioritization for rare disease

PRIORI-T is a tool used for rare disease phenotype-driven gene prioritisation. PRIORI-T was compared with other tools, such as DisGeNET and Open Targets. It was found to have better associations for rare disease phenotype-driven gene prioritisation. The tool has a high quality curated data, and is recommended in phenotype-driven gene prioritisation for rare disease studies.

Deep learning algorithm in rare diseases

A study was conducted on patients with rare neurological disorders (tuberous sclerosis complex (TSC)) to develop and test a deep learning algorithm and to detect signs in magnetic resonance imaging (MRIs). Axial images with and without tubers were extracted from MRIs of patients with TSC, attesting that deep learning algorithms are able to detect tubers in selected MRI images.

LipoDDx mobile application for rare lipodystrophy syndromes diagnosis

An article in Orphanet Journal of Rare Diseases (OJRD) highlights an innovative and free mobile app, LipoDDx that is able to deliver a diagnosis of Lipodystrophy syndromes, rare disorders with a very low prevalence and large phenotypic heterogeneity, and which are defined by a loss of adipose tissue combined with nutritional deprivation or exacerbated catabolism. Lipodystrophy syndromes have delays in diagnosis and misdiagnosis is also frequent.

LipoDDx uses dichotomous questions or choice of clinical signs from the app menu, and it is currently able to deliver a diagnosis in more than 40 rare lipodystrophy subtypes. This will help doctors that are not Lipodystrophy syndromes specialists. There is a need to analyse other cases and types of Lipodystrophy syndromes for more efficiency of LipoDDx free mobile app.

Summary of the edition of 26 June 2020

Editorial
Political news
Scientific news
And also...