Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials.

ABSTRACT: An increase in blood lipoprotein (a) [Lp(a)] levels, mostly genetically determined, has been identified as an independent risk factor of atherosclerotic cardiovascular disease. No drug has yet been approved that markedly lowers Lp(a) and thereby reduces residual cardiovascular risk. The aim of this article was to critically review the evidence from clinical development studies to date on the efficacy and safety of new RNA-based therapeutics for targeted lowering of Lp(a). PubMed/MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched without any language or date restriction up to November 5, 2022, and a total of 12 publications and 22 trial records were included. Several drugs were found that are currently in various stages of clinical development, such as the antisense oligonucleotide pelacarsen and the small interfering RNA molecule olpasiran and drugs coded as SLN360 and LY3819469. Among them, pelacarsen has progressed the most, currently reaching phase 3. All these drugs have so far shown satisfactory pharmacokinetic properties, consistently high and stable, dose-dependent efficacy in lowering Lp(a) even by more than 90%, with an acceptable safety profile in subjects with highly elevated Lp(a). In addition, reports of early clinical trials with pelacarsen imply a promising suppressive effect on key mechanisms of atherogenesis. Future research should focus on confirming these beneficial clinical effects in patients with lower average Lp(a) levels and clearly demonstrating the association between lowering Lp(a) and reducing adverse cardiovascular outcomes.

Access to orphan drugs - comparison across Balkan countries.

The aim of this study was to compare orphan drug access in a sample of Balkan countries: five EU Member States (Bulgaria, Croatia, Greece, Romania, Slovenia) and two EU Candidates (Serbia, Montenegro). The comparative analysis was based on a cross-sectional study and included medicinal products with an active orphan designation and market authorisation on January 1, 2017. Access to orphan drugs is an ongoing challenge in these countries. Three clusters of countries were identified in terms of orphan drug access: Greece and Slovenia, making the top tier, Romania, Bulgaria, and Croatia, being in the middle, and EU Candidates, Serbia and Montenegro, forming the bottom tier, where a substantial number of EU market approved orphan drugs was not even registered. Available public health resources and market size are probably among the contributing factors for such inequalities. Sizeable part of EMA market authorised orphan medicinal products is not even priced in the Balkan countries. This is a serious issue, which is putting rare disease patients from this region in a particularly vulnerable situation. There is a need for further improvement in accessibility of orphan drugs in the Balkan countries. Cross-border collaboration in the field of pricing, health technology assessment, and reimbursement negotiation of orphan drugs may help to address these challenges.

Growth of Global Publishing Output of Health Economics in the Twenty-First Century: A Bibliographic Insight.

BACKGROUND: Strong growth of interdisciplinary sciences might find exceptional example in academic health economics. We decided to observe the quantitative output in this science since the beginning of the twenty-first century. METHODS: Electronic search of the published literature was conducted in four different databases: one medical database-MEDLINE/PubMed, two general databases-Scopus/Elsevier and Web of Science (WoS), and one specialized health economic database-NHS Economic Evaluation Database (EED). The applied combination of key words was carefully chosen to cover the most commonly used terms in titles of publications dealing with conceptual areas of health economics. All bibliographic units were taken into account. RESULTS: Within the time horizon from January 1, 2000 to December 31, 2016, without language or limitations on bibliographic unit types, we identified an output ranging approximately from 60,345 to 88,246 records with applied search strategy in MEDLINE/PubMed, Scopus/Elsevier, and WoS. In NHS EED, we detected 14,761 records of economic evaluations of health interventions during the period in which database was maintained and regularly updated. With slightly more than one-third of the identified records, USA clearly dominates in this field. United Kingdom takes a strong second place with about 12% of identified records. Consistently, USA and UK universities are the most frequent among the top 15 affiliations/organizations of the authors of the identified records. Authors from Harvard University contributed to the largest number of the identified records. CONCLUSION: There is a clear evidence of both the upward stream of blossoming in health economics publications and its acceleration. Based on this bibliographic data set, it is difficult to distinguish the actual impact growth of this output provided dominantly by academia with modest contribution by pharmaceutical/medicinal device industry and diverse national government-based agencies. Further insight into the citation track record of these individual publications could provide helpful upgrade and a perspective on ongoing development.