Edition of 15 February 2019

On the 12 November 2018, Frontiers in Pharmacology published a study aiming to examine shares of reimbursed orphan drugs and agreement in reimbursement decision-making in different European Union Member States. It also looked at the influence of conditional approval or exceptional circumstances statuses granted by the European Medicines Agency (EMA) and of the type of the disease on reimbursement decisions. Their results show a considerable variation between EU countries, the highest agreement in reimbursement was reported between Italy and Spain and the lowest between Germany and England. The statuses (conditional approval and approval under exceptional circumstances) were generally negatively related to the prospect of reimbursement and were significantly associated with the type of the disease: oncology with conditional approval and metabolic with exceptional circumstances.

A study conducted in Spain and published in PharmacoEconomics Open journal intended to quantify the time and reimbursement associated with hospitalisations of patients with Philadelphia chromosome-negative (Ph−) relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukaemia (ALL) by collecting patient data from 1998 to 2014. In sum, the article states that almost all reimbursement was attributed to inpatient stays, that hospitalisations for R/R ALL are lengthy and that they incur very high cost.

An article from Pediatric Pulmonology sought to update cost estimates for cystic fibrosis (CF) focusing specifically on recent trends in healthcare expenditures for patients with CF in the United States. It reported a one-year CF prevalence of 1.1-1.4 per 10 000 adults and 2.9-3.0 per 10 000 children. The researchers also revealed that per-patient expenditures almost doubled for privately-insured CF patients between 2010 and 2016 from $67 000 to approximately $131 000 per patient.  This surge in cost was mainly linked to specialty drugs with a major contribution from new, genotype-targeted CFTR modulator medications.

In a study published by Value in Health a team of researchers evaluated the cost utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease. The findings revealed that the current price of Voretigene Neparvovec made it unlikely to reach cost effectiveness standards compared with standard of care even though it provided an additional 1,3 quality-adjusted life-years.  

A review in the Medicine Access@Point of Care highlights the need to improve market access to rare diseases therapies. The author stresses the opportunity for the pharma industry to partner with healthcare systems and address these issues. The article outlines a set of recommendations for the industry including to create links with patient organisations and physician societies so as to inform and educate decision makers and payers about the burden of disease, promote best practice in the rare disease field at an international level as well as collaboration in pilot projects and ensure the balance between value proposition of the drug and its price, taking into consideration payers’ flexibility. Finally, the article draws attention to the benefits that such partnerships could entail in middle-income and emerging markets.

The Journal of Market Access and Health Policy published an article on the 6 December 2018 arguing that the principles of individual utility and efficiency at the root of the theory of economic evaluation excludes key social values. The analysis, stemming from empirical evidence and four studies, indicates that when taking on the perspective of a citizen, individuals tend to prefer to divide the budget in an inclusive way, so that it does not leave out patients in need of treatments and services which are not cost-effective i.e. orphan drugs and treatments for ultra-rare diseases.

Concerned specifically about the persistent gap between medical need and the development of new medicines across countries in the case of cancer, immunological diseases, and orphan diseases, a paper published in Frontiers in Public Health reflected on solutions to optimise the use of new medicines taking into account rising costs and increasing budgetary pressures. The authors find that many activities exist prior the development and funding of new drugs under a system of universal healthcare such as horizon scanning. Considering the increasing resource pressures and the importance of unmet needs, the authors predict that such activities will continue to increase.

A study published in January by the Mayo Clinic Proceedings analysed if the US Food and Drug Administration approval of new drugs without randomisation led to more postmarketing safety-related label modifications. The paper states that drug approvals not supported by randomised controlled trials (RCTs) were associated with lower sample size which facilitated orphan drug designation, fast-track designation and accelerated approval. As a result they observe that approval of new drugs without supporting RCTs is associated with more postmarketing safety-related label modifications than drugs approved with supporting RCTs. Hence, they recommend for health care professionals to be well advised when prescribing these drugs, to give patients sufficient information about the limitations regarding safety data, and pay particular attention to unreported adverse effects.

A recent paper aimed to identify cross-border international registries led in Europe for rare endocrine conditions and to understand the extent of engagement with these registries within a network of reference centres (RCs) for rare endocrine conditions. The study uncovered the fundamental need to improve the general awareness as well as the participation in the registries. For instance, out of 27 registries referenced in the Orphanet and RD-Connect databases, Endo-ERN RCs were aware of 11 (41%) and of 21 registries recorded by the RC, RD-Connect and Orphanet had identified  less than 10 (48%).

A review article published in the Orphanet Journal of Rare Disease undertook an analysis to compare the impact of stand-alone registries, registries with biobanks, and rare disease biobanks on research outcomes in rare diseases. The findings illustrate fundamental differences between the resources. Indeed, stand-alone registries were found to be particularly beneficial for revealing the natural history of diseases, develop best practices, replace clinical trials and improve patient outcomes. However, they were limited in their capacity to conduct basic research unlike rare disease biobanks which were found to provide the infrastructure required to conduct such research. Nevertheless, these stand-alone rare disease biobanks did not collect comprehensive data or have an impact on clinical observations. So, the study concludes that registries with biobanks represent a crucial opportunity to boost rare disease research thanks to their capacity to link stand-alone registries and rare disease biobanks, and hence allow for the effective translation of basic research into clinical practice.

The current status of Online Mendelian Inheritance in Man (OMIM) is described in a recent article published in Nucleic Acids Research. The authors present the organisation of their catalog of genes and genetic phenotypes, as well as the OMIM Morbid Map Scorecard, which presents the cytogenetic locations of disorders that are described in OMIM.

An article published in Frontiers in Genetics with the aim of improving diagnostics for rare diseases adopted a phenotypic similarity method coupled with a machine learning method to build four diagnostic models. Each model established a list of the top ten candidate diseases. The results of the analysis of their outcome demonstrated that the diagnostic precision was high and that the models with machine learning methods worked best. As a means to support diagnosis in clinical application the authors developed a phenotype-based system with the four diagnostic models: Rare Disease Auxiliary Diagnosis (RDAD) with the objective to assist clinicians in diagnosing rare diseases.

A study to evaluate the utility of phenomic correlations in mitochondrial disease and Inherited metabolic disorders has been conducted and the paper published by Clinical Medicine. The Leigh Map, a gene-to-phenotype interaction network, with searchable elements for Leigh syndrome (a paediatric mitochondrial rare disorder) was produced comprising data on 92 genes and 275 phenotypes standardised in human phenotype ontology terms, with 80% predictive accuracy. The authors argue that despite certain challenges, the use of phenomics brings positive changes to clinical interventions and potentially improves the prognosis of patients affected by inherited metabolic disorders.

A study conducted last year set out to assess the value of genetic analysis as a confirmatory measure following the detection of suspected inborn errors of metabolism in the Spanish newborn mass spectrometry screening program. The researchers analysed DNA samples through next-generation sequencing. Finally, their findings corroborate the hypothesis that genetic analysis including next-generation sequencing panels are a good means to confirm suspected inborn errors of metabolism detected in newborn screening programs, and that biochemical tests are useful tools to improve a diagnosis’ precision and clarity.

A screening programme is currently being developed by the Dubai Health Authority with the objective of improving early detection, intervention and rehabilitation for newborns. To assist parents and ensure that they do not miss the screening visits for their child from their birth until they reach six years old, notifications will be sent through an app called Tifli.