Edition of 28 October 2024

International News

Leveraging new technologies to accelerate rare disease diagnosis: Recommendations from an IRDiRC Task Force

A new article has been published in the Orphanet Journal of Rare Diseases by the International Rare Diseases Research Consortium (IRDiRC)’s Task Force on Integrating New Technologies for Rare Disease Diagnosis (INTRDD Task Force). The article proposes recommendations for how emerging diagnostic technologies can be applied to accelerate rare disease diagnosis, while considering disparities in accessibility between countries.

IRDiRC’s primary goal is to ensure that all patients with a suspected rare disease receive a diagnosis within one year, provided their disorder is documented in medical literature. The INTRDD Task Force was created to work in support of this goal by addressing challenges facing the implementation of advances in diagnostic technologies. In this article, they use their work to date to propose a stepwise application of such technologies, including genomics, functional testing and model systems, and artificial intelligence (AI) in diagnostic pathways.

The authors identify a number of innovative technologies in varying states of development which can enable RD diagnosis. These include:

Genomic technologies such as long read sequencing, episignature, genome sequencing and exome sequencing
Functional genomics technologies such as multi-omics, high throughput functional studies, reverse phenotyping, model systems and organisms and RNA sequencing
Other technologies, including artificial intelligence, phenotyping, data and metadata sharing and gene and variant matching

In order to achieve equitable access to RD diagnosis, the Task Force emphasises the importance of data management principles such as FAIR (Findability, Accessibility, Interoperability, Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics). They also discuss the importance of continuing medical education in genomics, and potential strategies for overcoming challenges related to genomic diversity.

Overall, these recommendations are the first step towards establishing a framework for incorporating innovative technologies into rare disease clinical practice. By working to further develop these emerging technologies and make them more equitably accessible, IRDiRC is moving one step closer to their goal of accelerating diagnosis for people living with an undiagnosed rare disease.

Understanding the rare disease funding landscape: Findings of the IRDiRC Funding Models for Rare Diseases Research Task Force

In a recent article published in Rare Disease and Orphan Drugs Journal, members of the International Rare Diseases Research Consortium (IRDiRC)’s Funding Models for Rare Diseases Research Task Force (FMRDR Task Force) present their findings on contributing factors and investment principles in funding for rare disease research.

The FMRDR Task Force is one of the many Task Forces and Working Groups working within IRDiRC to advance the understanding and impact of rare disease diagnosis and treatment on a global scale. Formed in 2023, it is continuing the work of the Chrysalis Task Force which was conceived as a link between industry, funders and advocates, with the ultimate goal of overcoming barriers specific to rare disease research through an understanding of the criteria for investment in this area.

The new article identifies return on investment (ROI) as a guiding principle for decisions to fund rare disease research. However, the precise definition of ROI varied between different types of funders. For example, public funders and patient groups consider research outcomes and resulting impacts on population health to be the “return” on their investment. On the other hand, venture investors and pharmaceutical companies are primarily concerned with a financial ROI. The authors also identified a diversity in the types of funding instruments used, including both major investment and venture-type approaches. All types of funders did however share funding requirements, such as scientific quality and health economics.

In addition to providing an overview of the current landscape of rare disease funding, the Task Force identified several knowledge gaps to be further addressed through targeted research in order to better understand and leverage different types of funding opportunities. These are:

Understanding how stakeholders such as researchers, funders, advocates, regulatory agencies, and policymakers interact in specific rare and ultra-rare diseases
Understanding how costs at every stage of diagnostic and therapeutic development could be managed in a sustainable manner
Understanding the impact of partnerships between different interested parties in rare diseases

Overall, the Task Force’s findings demonstrate the ongoing need for flexibility in supporting rare disease funding. The authors emphasise the importance of further research in this area, and highlight the benefits people living with a rare disease stand to gain through a continued candid dialog and innovation between interested parties.

Inequities in the US rare disease community: Findings from a NORD & RDDC survey

The United States’ National Organization for Rare Disorders (NORD) has published the findings from a survey conducted in collaboration with the Rare Disease Diversity Coalition (RDDC), which investigated the barriers faced by underrepresented patients with rare diseases and their caregivers. This study, which involved over 2,800 participants throughout the United States, reveals key insights into the challenges and potential solutions for making rare disease care equitably accessible for all.

Among the study participants, 48% met the definition of “unrepresented.” For the purposes of this study, this term was defined as individuals belonging to one or more of the following groups:

Living below the federal poverty limit
Black, Indigenous, People of Colour (BIPOC)
Hispanic/Latino
LGBTQ+
Rural populations

The survey asked participants about 14 potential barriers to accessing care. For seven of these, over a quarter of respondents reported that they led to delays or avoidance of care. These included issues related to emotional well-being, financial constraints, and more. The most commonly reported barrier was feeling overwhelmed from managing life, care, or caregiving responsibilities, which was encountered by 50% of participants. However, this proportion was higher among the underrepresented population, rising as high as 72% among the LGBTQ+ community.

In order to address these barriers and render access to rare disease care more equitable, the report makes the following recommendations:

Increase access to genetic counselling during the diagnostic process, including the expansion of affordable options and training for clinicians across the healthcare system
Expand insurance guidance and coverage through the introduction and/or expansion of financial assistance programs, more support from financial navigators, and upholding the commitments of the Affordable Care Act
Understand and correct for the profound impacts of poverty on health access through measures such as proactive outreach, financial and administrative assistance, and assistance with food and shelter
Address the mental health crisis facing patients and caregivers through culturally relevant and appropriate means
Promote engagement and inclusion in daily life, including through efforts to raise awareness amongst the general public

Additionally, the report emphasises the importance of aligning these recommendations with existing and future policy campaigns, as well as continuing to assess and elaborate recommendations in this domain as the rare disease landscape evolves. The hope is that, by understanding the gaps that exist in the healthcare system and their underlying causes, it will be possible to take action to narrow or even close them, and ensure that all individuals have equal access to high-quality, appropriate care.

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European News

Orphan Drugs

FDA: Fifteen new market authorisations with orphan designation granted from July to September 2024

From July to September, the FDA accorded market authorisation to the following medicinal products with an orphan designation:

Teclera, for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotheramy, are HLA-A*02:01P, -A*02:02P, -A01:03P, or -A*02:06P positive and whose tumor expresses the melanoma-associated antigen A4 (MAGE-A4) antigen as determined by FDA-approved or cleared companion diagnostic devices
Nexobrid, for eschar removal in adults and pediatric patients with deep partial thickness (DPT) and/or full thickness (FT) thermal burns
Niktimvo, for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40kg
Brineura, to slow the loss of ambulation in pediatric patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency
Lymphir, for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy
Prevymis, as prophylaxis of cytomegalovirus (CMV) disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])
Prevymis, as prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant
Livmarli, for the treatment of cholestatic pruritus in patients 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC)
Yorvipath, for the treatment of hypoparathyroidism in adults
Livdelzi, for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA
Voranigo, for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation following surgery including biopsy, sub-total resection, or gross total resection
Miplyffa, for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older
Fasenra, for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA)
Sarclisa, in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
Aqneursa, for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing greater than or equal to 15 kg
Filspari, to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression

FDA: One hundred thirty-eight new orphan designations approved from July to September 2024

From July to September, the FDA granted orphan designations for the following indications:

Treatment of primary mitochondrial myopathy
Treatment of malignant glioma
Treatment of adrenocortical carcinoma
Treatment of acute lymphoblastic leukemia
Treatment of mesothelioma
Treatment of gastric cancer, including gastroesophageal junction cancer
Treatment of small cell lung cancer
Treatment of Duchenne muscular dystrophy
Treatment of systemic sclerosis
Treatment of pachyonychia congenita
Treatment of amyotrophic lateral sclerosis (ALS)
Treatment of hepatocellular carcinoma
Treatment of Charcot-Marie-Tooth disease type 2C
Treatment of primary hyperoxaluria
Treatment of neuroendocrine carcinoma
Treatment of spinocerebellar ataxia
Treatment of myotonic dystrophy type 1
Treatment of Duchenne muscular dystrophy
Treatment of Niemann-Pick type C
Treatment of retinitis pigmentosa
Treatment of Phelan-McDermid syndrome
Treatment of acute lymphoblastic leukemia
Treatment of spina bifida
Treatment of pulmonary arterial hypertension
Treatment of small cell lung cancer
Treatment of Friedreich's ataxia
Treatment of amyotrophic lateral sclerosis (ALS)
Treatment of pancreatic cancer
Treatment of T-cell lymphoma
Treatment of stiff person syndrome
Treatment of pancreatic cancer
Treatment of neurofibromatosis type 2
Treatment of recurrent respiratory papillomatosis
Treatment of neuroendocrine carcinoma
Treatment of cholangiocarcinoma
Treatment of systemic sclerosis
Treatment of Menkes disease
Treatment of otoferlin-mediated hearing loss
Treatment of soft tissue sarcomas
Treatment of X-linked retinoschisis
Treatment of acute myeloid leukemia
Treatment of idiopathic pulmonary fibrosis
Treatment of beta-thalassemia
Treatment of acute myeloid leukemia
Treatment of pulmonary arterial hypertension (PAH)
Treatment of Duchenne muscular dystrophy
Treatment of esophageal cancer
Treatment of neuroendocrine carcinoma
Treatment of idiopathic pulmonary fibrosis
Treatment of hemophilia A
Treatment of pulmonary arterial hypertension
Treatment of Kawasaki disease
Treatment of Angelman syndrome
Treatment of Phelan-McDermid syndrome
Treatment of Kleine-Levin syndrome
Treatment of pancreatic cancer
Treatment of Wilson Disease
Treatment of Glucosse transporter type 1 deficiency syndrome
Treatment of progressive familial intrahepatic cholestasis
Treatment of homocystinuria
Treatment of cholangiocarcinoma (CCA)
Treatment of soft tissue sarcoma
Treatment of AT-rich interactive domain-containing protein 1a (ARID1a)-deficient ovarian cancer, fallopian tube cancer, and primary peritoneal cancer
Treatment of primary biliary cholangitis
Treatment of Duchenne muscular dystrophy
Treatment of neuroblastoma
Treatment of soft tissue sarcoma
Treatment of Ewing sarcoma
Treatment of acute graft-versus-host disease
Treatment of chronic pancreatitis
Treatment of Wilson Disease
Treatment of Menkes disease
Treatment of T-Cell lymphoma
Treatment of primary immune thrombocytopenia (ITP)
Treatment of hemophilia B
Treatment of acute lymphocytic leukemia
Treatment of acute leukemias of ambiguous lineage
Treatment of Hutchinson Gilford progeria syndrome (HGPS) and Progeroid Laminopathies (PL)
Treatment of polycythemia vera
Treatment of Duchenne muscular dystrophy and Becker muscular dystrophy
Treatment of PIK3CA-Related Overgrowth Spectrum (PROS)
Treatment of pancreatic cancer
Treatment of ROS1-positive, NTRK positive, ALK-positive, LTK-positive, ACK1-positive, or DDR1-positive non-small cell lung cancer (NSCLC)
Treatment of retinoblastoma
TReatment of amyotrophic lateral sclerosis
Treatment of small cell lung cancer
Prevention of acute graft-versus-host disease (aGvHD)
Treatment of Leigh syndrome
Treatment of Duchenne muscular dystrophy
Treatment of Aicardi-Goutieres syndrome
Treatment of gastric cancer
Treatment of myelodysplastic syndromes
Treatment of multisystemic smooth muscle dysfunction syndrome (MSMDS) caused by ACTA2-RI79H mutation
Treatment of Myotonic Dystrophy Type 1
Treatment of Duchenne muscular dystrophy
Treatment of retinitis pigmentosa
Treatment of acute lymphoblastic leukemia
Treatment of Fabry disease
Treatment of mucopolysaccharidosis IVA (Morquio A syndrome)
Treatment of Gaucher Disease
Treatment of propionic acidemia
Treatment of NPHP5 mutation-associated retinal dystrophy
Treatment of retinal dystrophy due to mutations in the lebercilin gene, including Leber congenital amaurosis
Treatment of neurotrophic keratitis
Treatment of KCNT1-related Epilepsy
Treatment of uveal melanoma
Treatment of systemic sclerosis
Treatment of severe combined immunodeficiency (SCID)
Treatment of pancreatic cancer
Treatment of pancreatic cancer
Treatment of congenital athymia
Treatment of Hirschsprung disease
Treatment of Dravet syndrome
Treatment of cholangiocarcinoma
Treatment of transthyretin amyloidosis
Treatment of acute myeloid leukemia
Treatment of Duchenne muscular dystrophy (DMD)
Treatment of X-linked hypophosphatemia
Treatment of Glanzmann thrombasthenia
Treatment of gastric cancer
Treatment of junctional ectopic tachycardia
Treatment of primary hyperoxaluria
Treatment of Ewing's sarcoma
Treatment of prion disease
Treatment of congenital long QT syndrome
Treatment of hereditary angioedema
Treatment of hemophilia A
Treatment of Duchenne muscular dystrophy
Treatment of sickle cell disease
Treatment of autosomal recessive retinitis pigmentosa due to CNGB1 mutations
Treatment of congenital hereditary endothelial dystrophy
Treatment of congenital hereditary endothelial dystrophy
Treatment of familial dysautonomia
Treatment of Friedreich's ataxia
Treatment of Multiple Sulfatase Deficiency
Treatment of urea cycle disorders
Treatment of lymphatic malformations
Treatment of glioblastoma multiforme in pediatric patients
Treatment of acute myeloid leukemia
Treatment of giant cell arteritis

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Quality of Care

Experience of an Undiagnosed Diseases Program in China to accelerate diagnosis and improve rare disease care

A new article has been published in Frontiers in Public Health which presents the experience of a paediatric undiagnosed diseases program (UDP) in Fudan, China.

Beginning in March 2016, the Children’s Hospital of Fudan University ran a UDP which aimed to achieve a diagnosis for children presenting with serious unexplained symptoms using a multidisciplinary approach. This study aims to demonstrate how such an approach can accelerate rare disease diagnosis in China by describing the project’s outcomes and findings.

Between January 2017 and December 2021, 758 cases were examined within the Fudan UDP. Among these, 469 received genetic testing, yielding a genetic diagnosis rate of 15.8%. The authors found that the project had a sensitivity of 94.5%, a specificity of 86.4%, a positive predictive value of 92.8% and a negative predictive value of 89.5%.

The article also highlights specific success stories from the UDP. These included a toddler who had been suffering from anaemia with an unknown cause and which had been unresponsive to oral iron therapy, whose genomic testing was able to identify the causal mutation. Another success was the correction of a previous diagnosis of a three-year-old girl thought to have infective endocarditis. After 2 years of ineffective treatment, further investigation under the UDP led to a corrected diagnosis of systemic lupus erythematosus.

The UDP at Children’s Hospital of Fudan University was inspired by the program created by existing UDPs around the world, such as the one created by the NIH in the United States. It was conceived of as a pilot project to assess the feasibility and effectiveness of both a long-term UDP in China and a medical system for rare disease identification. Based on the observed results, the authors believe that implementing a nation-wide UDP based on that which was piloted in Fudan would greatly improve care quality, and deliver new hope to children living with an undiagnosed disease and their families.

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Screening and Prenatal Diagnosis

Ethical, Legal and Social

Quality of LIfe

Common factors affecting health-related quality of life across rare diseases

A new study has been published in Genetics in Medicine Open which aims to uncover patient- and disease-specific correlates of health-related quality of life (HRQL) across a diverse set of rare diseases.

A number of studies exist which investigate the relationship between rare diseases and HRQL. However, most of these studies are limited to a single or select group of rare diseases, often in a limited geographical area. In order to develop and evaluate platform-based interventions on HRQL which tackle multiple rare diseases at a time, there is therefore a need for a more global understanding of the impact of rare diseases as a group on HRQL. This study was conducted in order to close this gap, and to facilitate more targeted interventions aimed at improving HRQL in multiple rare diseases.

In pursuit of this goal, researchers conducted an international online survey of rare disease patients and caregiver proxies affected by various rare diseases. By analysing the responses, they were able to identify several predictors of HRQL common to participants. In particular, identifying as disabled and being affected by a lower prevalence disease were significantly correlated with lower HRQL. Additional correlates identified included increased pain, decreased ability to perform usual activities, older caregiver age, and identifying as male.

The findings presented in this study represent an effort to close a gap in the knowledge on HRQL in rare diseases. The authors identify points of interest to be explored in further research, and provide a knowledge foundation upon which policies can be developed and funding priorities for research can be identified to improve health care delivery and quality of life across all rare diseases.

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International News

European News

Orphan Drugs

Quality of Care

Screening and Prenatal Diagnosis

Quality of LIfe

Registries and Biobanks

Summary of the edition of 28 October 2024

Editorial

Political news

Scientific news

And also...

International News

Leveraging new technologies to accelerate rare disease diagnosis: Recommendations from an IRDiRC Task Force

Understanding the rare disease funding landscape: Findings of the IRDiRC Funding Models for Rare Diseases Research Task Force

Towards better social protection for PLWRD: A new partnership between RDI & the P4H Network

Inequities in the US rare disease community: Findings from a NORD & RDDC survey

Towards the implementation of Canada's National Strategy for Drugs for Rare Diseases: Two new reports published

European News

Apply to join the ERDERA Multistakeholder Advisory Board

New EMA & HMA guiding principles on LLM use

Public consultation on implementing joint scientific consultations under the HTA Regulation

Commission guidance on the validity of clinical studies for Health Technology Assessment

New CTIS portal now live

EURORDIS: Call for manuscripts on drug repurposing

Orphan Drugs

EMA: Six new market authorisations with an orphan designation from July-September 2024

EMA: Thirty-four orphan designations accorded by the COMP from July to September 2024

FDA: Fifteen new market authorisations with orphan designation granted from July to September 2024

FDA: One hundred thirty-eight new orphan designations approved from July to September 2024

Quality of Care

Experience of an Undiagnosed Diseases Program in China to accelerate diagnosis and improve rare disease care

Screening and Prenatal Diagnosis

Understanding barriers to genomic NBS in Europe: A Delphi consensus study

Ethical, Legal and Social

A framework for better health equity among older adults living with a rare disease

Health literacy among adults with rare diseases: A literature review

Quality of LIfe

Common factors affecting health-related quality of life across rare diseases

Registries and Biobanks

Assessing registry feasibility for common core datasets: The SATURN methodology

Summary of the edition of 28 October 2024

Editorial

Political news

Scientific news

And also...