scholarly journals From Off-Label to Repurposed Drug in Non-Oncological Rare Diseases: Definition and State of the Art in Selected EU Countries

2017 ◽  
Vol 1 ◽  
pp. maapoc.0000016 ◽  
Author(s):  
Paola Minghetti ◽  
Elena P. Lanati ◽  
Josie Godfrey ◽  
Oriol Solà-Morales ◽  
Olivier Wong ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Drug Repurposing ◽  
Orphan Drugs ◽  
New Drugs ◽  
Success Rates ◽  
Great Opportunity ◽  
Off Label ◽  
Research Activities ◽  
Oncological Diseases ◽  
Repurposed Drugs

Introduction Almost 8,000 rare diseases exist worldwide, affecting approximately 350 million people. Nevertheless, only 5% receive a specific authorized or licensed treatment. The need for effective and rapidly available therapies is still unmet for many patients. Objective The objective is to define repurposing versus off-label drugs, and to evaluate pathways of repurposed drugs for rare non-oncological diseases in Italy, France, England, and Spain (the EU4 countries). Methods This original paper is based on 3 research activities: (i) a nonsystematic literature research; (ii) a questionnaire-based survey to regulatory experts; and (iii) research on approval timelines and therapy prices of repurposed non-oncology orphan drugs. Official approval dates in England are not available if the National Institute for Health and Care Excellence does not appraise the products. Results Only France provides a specific adaptive pathway from off-label to repurposed drugs. Pricing and reimbursement assessment for the drug samples varied across the EU4 countries: time-to-market for repurposed drugs versus new drugs is longer in all analyzed countries; that is, 979 days versus 462 days in Italy, 502 days versus 350 days in France, and 624 versus 378 days in Spain. Repurposed drugs have higher success rates from development to approval than novel drugs (30% vs. 11%). Small- and medium-sized enterprises owned 9 of 12 repurposed non-oncology orphan drugs, of which only 4 were reimbursed in all EU4 countries. Prices were more homogeneous across EU4 although the reimbursement rates were different. Conclusions Drug repurposing represents a great opportunity to treat rare non-oncological diseases. However, a more homogenous assessment across EU4 could ensure reimbursement and prices high enough to reward organizations investing in this field.

scholarly journals Off-Label Medication: From a Simple Concept to Complex Practical Aspects

2021 ◽  
Vol 18 (19) ◽  
pp. 10447
Author(s):  
Carmen-Maria Rusz ◽  
Bianca-Eugenia Ősz ◽  
George Jîtcă ◽  
Amalia Miklos ◽  
Mădălina-Georgiana Bătrînu ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Drug Repurposing ◽  
Regulatory Agencies ◽  
Systematic Research ◽  
Clinical Practices ◽  
Safe Practice ◽  
Safety Issues ◽  
Off Label ◽  
Simple Concept ◽  
Approved Drugs

Off-label use of drugs is widely known as unapproved use of approved drugs, and it can be perceived as a relatively simple concept. Even though it has been in existence for many years, prescribing and dispensing of drugs in an off-label regimen is still a current issue, triggered especially by unmet clinical needs. Several therapeutic areas require off-label approaches; therefore, this practice is challenging for prescribing physicians. Meanwhile, the regulatory agencies are making efforts in order to ensure a safe practice. The present paper defines the off-label concept, and it describes its regulation, together with several complex aspects associated with clinical practices regarding rare diseases, oncology, pediatrics, psychiatry therapeutic areas, and the safety issues that arise. A systematic research of the literature was performed, using terms, such as “off-label”, ”prevalence”, ”rare diseases”, ”oncology”, ”psychiatry”, ”pediatrics”, and ”drug repurposing”. There are several reasons for which off-label practice remains indispensable in the present; therefore, efforts are made worldwide, by the regulatory agencies and governmental bodies, to raise awareness and to ensure safe practice, while also encouraging further research.

Repurposing Drugs to Combat Drug Resistance in Leprosy: A Review of Opportunities

2021 ◽  
Vol 25 ◽  
Author(s):  
Mukul Sharma ◽  
Pushpendra Singh
Keyword(s):  
Synergistic Effects ◽  
Drug Repurposing ◽  
New Drugs ◽  
Resistance Testing ◽  
Promising Alternative ◽  
Drug Molecules ◽  
Conventional Drug ◽  
Repurposed Drugs ◽  
Multiple Drugs

: Leprosy is caused by extremely slow-growing and uncultivated mycobacterial pathogens, namely Mycobacterium leprae and M. lepromatosis. Nearly 95% of the new cases of leprosy recorded globally are found in India, Brazil, and 20 other priority countries [WHO, 2019], of which nearly two-thirds of the cases are reported in India alone. Currently, leprosy is treated with dapsone, rifampicin, and clofazimine, also known as multi-drug therapy [MDT], as per the recommendations of WHO since 1981. Still, the number of new leprosy cases recorded globally has remained constant in the last one-decade ,and resistance to multiple drugs has been documented in various parts of the world, even though relapses are rare in patients treated with MDT. Antimicrobial resistance testing against M. leprae or the evaluation of the anti-leprosy activity of new drugs remains a challenge as leprosy bacilli do not grow in vitro. Besides, developing a new drug against leprosy through the conventional drug development process is not economically attractive or viable for pharma companies. Therefore, a promising alternative is the repurposing of existing drugs/approved medications or their derivatives for assessing their anti-leprosy potential. It is an efficient method to identify novel medicinal and therapeutic properties of approved drug molecules. Any combinatorial chemotherapy that combines these repurposed drugs with the existing first-line [MDT] and second-line drugs could improve the bactericidal and synergistic effects against these notorious bacteria and can help in achieving the much-cherished goal of “leprosy-free world”. This review highlights novel opportunities for drug repurposing to combat resistance to current therapeutic approaches.

Dare voce ai pazienti nella ricerca sulle malattie rare e sui famaci orfani / Giving patients a voice in the rare diseases and orphan drugs research

2018 ◽  
Vol 67 (1) ◽  
pp. 25-40
Author(s):  
Elena Mancini ◽  
Roberta Martina Zagarella
Keyword(s):  
Clinical Trials ◽  
Rare Diseases ◽  
Patient Reported Outcomes ◽  
Narrative Medicine ◽  
Orphan Drugs ◽  
New Drugs ◽  
Patient Centered ◽  
Patient Reported ◽  
Critical Issues ◽  
The Impact

L’articolo ha l’obiettivo di mettere in luce potenzialità e criticità dell’inclusione della prospettiva dei pazienti nella ricerca sulle malattie rare e sui farmaci orfani. A tal fine, nella prima parte, si propone un’analisi epistemologica dell’utilizzo dei racconti dell’esperienza individuale della malattia nella ricerca scientifica e nei trial clinici, facendo emergere, anche attraverso gli strumenti della medicina narrativa, le sfide teoriche e operative poste dall’inclusione della soggettività del paziente e del vissuto di malattia nonché l’importanza della valorizzazione della prospettiva del paziente, sia in generale sia nella ricerca sulle malattie rare e sui farmaci orfani. Nella seconda parte, il testo analizza in particolare il ruolo degli esiti riportati dai pazienti o Patient Reported Outcomes (PROs), misure per la valutazione complessiva della salute basate sulla prospettiva dei pazienti stessi, incentrandosi sulla sperimentazione clinica nel campo delle malattie rare. In questo contesto, infatti, i racconti di malattia, raccolti e valorizzati da fonti istituzionali e associazioni di pazienti, hanno contribuito a far emergere importanti questioni critiche e difficoltà nell’impiego di outcome centrati sul paziente nello sviluppo di nuovi farmaci e trattamenti, generando una serie di documenti e raccomandazioni relative al loro utilizzo per il benessere della comunità dei malati rari. ---------- This paper aims to highlight the potentiality and criticality of including patients’ perspective in rare diseases and orphan drugs research. In the first part, we propose an epistemological analysis of individual narrations of disease experience as they are used in scientific research and clinical trials. With the help of narrative medicine approach, this analysis points out theoretical and operational challenges of a perspective that includes patient’s subjectivity and illness experience. Furthermore, it reveals the significance of patients’ standpoints in general and in rare diseases as well as in the orphan drugs research. The second part of our article focuses on the role of the Patient reported Outcomes (PROs) – which are measures for the health’s overall assessment based on patient’s perspective – by investigating the impact on clinical trials for rare diseases. In this context, illness stories, which are collected and promoted by institutional sources and patients’ associations, contribute to underline important critical issues at stake in the employment of patient-centered outcomes both in new drugs and in the treatments development. Moreover, these stories are crucial to elaborate documents and recommendations concerning the use of PROs for the rare patients’ community welfare.

scholarly journals Drug Repurposing: A Paradigm Shift in Drug Discovery

2020 ◽  
Vol 5 (04) ◽  
pp. 60-68
Author(s):  
Saravanan Jayaram ◽  
Emdormi Rymbai ◽  
Deepa Sugumar ◽  
Divakar Selvaraj
Keyword(s):  
Drug Discovery ◽  
Success Rate ◽  
Chemical Structure ◽  
Target Identification ◽  
Drug Repurposing ◽  
New Drugs ◽  
Attractive Option ◽  
Traditional Drug ◽  
Repurposed Drugs

The traditional methods of drug discovery and drug development are a tedious, complex, and costly process. Target identification, target validation; lead identification; and lead optimization are a lengthy and unreliable process that further complicates the discovery of new drugs. A study of more than 15 years reports that the success rate in the discovery of new drugs in the fields of ophthalmology, cardiovascular, infectious disease, and oncology to be 32.6%, 25.5%, 25.2% and 3.4%, respectively. A tedious and costly process coupled with a very low success rate makes the traditional drug discovery a less attractive option. Therefore, an alternative to traditional drug discovery is drug repurposing, a process in which already existing drugs are repurposed for conditions other than which were originally intended. Typical examples of repurposed drugs are thalidomide, sildenafil, memantine, mirtazapine, mifepristone, etc. In recent times, several databases have been developed to hasten drug repurposing based on the side effect profile, the similarity of chemical structure, and target site. This work reviews the pivotal role of drug repurposing in drug discovery and the databases currently available for drug repurposing.

scholarly journals A Literature-Based Knowledge Graph Embedding Method for Identifying Drug Repurposing Opportunities in Rare Diseases

2019 ◽  
Author(s):  
Daniel N. Sosa ◽  
Alexander Derry ◽  
Margaret Guo ◽  
Eric Wei ◽  
Connor Brinton ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Drug Repurposing ◽  
Graph Embedding ◽  
Capital Requirements ◽  
Biomedical Literature ◽  
New Drugs ◽  
Global Network ◽  
Knowledge Graph ◽  
Promising Alternative ◽  
Embedding Method

One in ten people are affected by rare diseases, and three out of ten children with rare diseases will not live past age five. However, the small market size of individual rare diseases, combined with the time and capital requirements of pharmaceutical R&D, have hindered the development of new drugs for these cases. A promising alternative is drug repurposing, whereby existing FDA-approved drugs might be used to treat diseases different from their original indications. In order to generate drug repurposing hypotheses in a systematic and comprehensive fashion, it is essential to integrate information from across the literature of pharmacology, genetics, and pathology. To this end, we leverage a newly developed knowledge graph, the Global Network of Biomedical Relationships (GNBR). GNBR is a large, heterogeneous knowledge graph comprising drug, disease, and gene (or protein) entities linked by a small set of semantic themes derived from the abstracts of biomedical literature. We apply a knowledge graph embedding method that explicitly models the uncertainty associated with literature-derived relationships and uses link prediction to generate drug repurposing hypotheses. This approach achieves high performance on a gold-standard test set of known drug indications (AUROC = 0.89) and is capable of generating novel repurposing hypotheses, which we independently validate using external literature sources and protein interaction networks. Finally, we demonstrate the ability of our model to produce explanations of its predictions.

scholarly journals Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Sweta Shah ◽  
Marc Marie Dooms ◽  
Sofia Amaral-Garcia ◽  
Mariana Igoillo-Esteve
Keyword(s):  
Rare Diseases ◽  
Neurodegenerative Disorders ◽  
Low Frequency ◽  
Drug Repurposing ◽  
Wolfram Syndrome ◽  
Pharmaceutical Companies ◽  
Time Saving ◽  
Life Threatening ◽  
Repurposed Drugs

Rare diseases are life-threatening or chronically debilitating low-prevalent disorders caused by pathogenic mutations or particular environmental insults. Due to their high complexity and low frequency, important gaps still exist in their prevention, diagnosis, and treatment. Since new drug discovery is a very costly and time-consuming process, leading pharmaceutical companies show relatively low interest in orphan drug research and development due to the high cost of investments compared to the low market return of the product. Drug repurposing–based approaches appear then as cost- and time-saving strategies for the development of therapeutic opportunities for rare diseases. In this article, we discuss the scientific, regulatory, and economic aspects of the development of repurposed drugs for the treatment of rare neurodegenerative disorders with a particular focus on Huntington’s disease, Friedreich’s ataxia, Wolfram syndrome, and amyotrophic lateral sclerosis. The role of academia, pharmaceutical companies, patient associations, and foundations in the identification of candidate compounds and their preclinical and clinical evaluation will also be discussed.

The Novel Drugs of 2015 – An Extraordinary Growth of Innovative Pharmaceuticals

2016 ◽  
Vol 9 (4) ◽  
pp. 3331-3336
Author(s):  
D. Samba Reddy ◽  
Savitha Reddy
Keyword(s):  
Rare Diseases ◽  
Prescription Drugs ◽  
Orphan Drugs ◽  
Pharmaceutical Products ◽  
New Drugs ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
Novel Drugs ◽  
Drug Approvals ◽  
Tract Infections

The FDA has approved 45 new drugs in 2015, a record approval in two decades, indicating another year of excellent innovation and productivity. There are many regulatory pathways at the FDA for the approval of novel drugs. Sixteen drugs (36%) were First-in-Class with a new or unique mechanism of action for treating a disease. About 29% of the new drugs are biologics. Moreover, 21 of 45 (47%) are orphan drugs for the treatment of rare diseases. The FDA approved many new drugs to treat various forms of cancer, urinary tract infections, chronic hepatitis C, cystic fibrosis, irritable bowel syndrome, heart failure, and high cholesterol, as well as the first approved reversal agent for a commonly-used blood thinner.  For the second consecutive year, the FDA approved more “orphan” drugs for rare diseases than any previous year in recent history. From 2006 through 2014, the FDA averaged about 28 novel drug approvals per year. Such products represent innovation and provide important new therapies for patients worldwide. Despite such record new drug approvals, there is a continued productivity crisis in R&D due to a progressive rise in cost for drug discovery and development. The U.S. pharmaceutical market is forecasted to reach $548 billion by 2020. The prices appear to be increasing faster for generic and branded prescription drugs. Overall, faster development and regulatory review contributed to a spike in record approval of innovative pharmaceutical products in 2015

scholarly journals Letter of Editor

2020 ◽  
Vol 1 ◽  
Author(s):  
Editorial Office
Keyword(s):  
Rare Disease ◽  
Orphan Drug ◽  
Rare Diseases ◽  
Publishing House ◽  
Orphan Drugs ◽  
New Drugs ◽  
Medical Community ◽  
Great Promise ◽  
Original Research ◽  
Small Contribution

We are pleased to announce a new addition to SciencePower Publishing House, LLC journal collection: Journal of Rare Diseases and Orphan Drugs (JRDOD), a peer-reviewed open-access medical journal that publishes original research, reviews, case reports, and letters covering a broad field of its specialty. Why do we need a new journal? Because the science moves fast all around the Planet and new technology opened new horizons for the prevention and treatment of rare and genetically based disorders. Rare disease and disorders often need a multidisciplinary care team, deep knowledge of healthcare providers, and extensive patients’ and patient families’ support. It may take years until a disease is recognized and/or diagnosed. Spreading knowledge about rare disease conditions among biomedical scientists and physicians from the different subspecialty fields including genetics, pediatrics, cardiology, pulmonary, gastroenterology, rheumatology, neurology, dietary science, and other related disciplines is one of the goals of this journal, which we will be widely advertised within the medical community. Patients with special conditions could be “Rare, but Not Alone” and we want to add our voice to those patient advocacies. We also want to spread knowledge about orphan drugs. Well known fact that an orphan drug is a medication (pharmaceutical) that remains underdeveloped due to the lack of a company to find the drug profitable because the numbers of patients, who will benefit from the treatment, are small and so the potential market for new drugs to treat these rare diseases is also small. This situation fortunately somewhat changed in 1983, when the U.S. Congress passed the Orphan Drug Act. It facilitated and charged the orphan drugs' developmental landscape. Nowadays the FDA established the Office of Orphan Product Development (OOPD) to help with the development of orphan drugs (and other medical products for rare disorders), including FDA support for research grants. The international medical community has recognized the need to increase research and development of orphan drugs. We hope that our journal will be a small contribution to the promotion of wellbeing of people with rare disease conditions. Our publisher motto is "Superbi progressu aspiramus ad maximum" (the proud aspire to great promise). Please, consider submitting your next manuscript to the Journal of Rare Diseases and Orphan Drugs.

scholarly journals New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis

2018 ◽  
Vol 44 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Denise Rossato Silva ◽  
Margareth Dalcolmo ◽  
Simon Tiberi ◽  
Marcos Abdo Arbex ◽  
Marcela Munoz-Torrico ◽  
...  
Keyword(s):  
New Drugs ◽  
Special Focus ◽  
Drug Resistant ◽  
Success Rates ◽  
Duration Of Treatment ◽  
Drug Resistant Tuberculosis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Repurposed Drugs

ABSTRACT Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the “white plague”, and promising results are being reported.

Potential Interactions of the Orphan Drug Act and Pharmacogenomics: A Flood of Orphan Drugs and Abuses?

2005 ◽  
Vol 31 (2-3) ◽  
pp. 365-380 ◽  
Author(s):  
David Loughnot
Keyword(s):  
Orphan Drug ◽  
Rare Diseases ◽  
Orphan Drugs ◽  
The United States ◽  
New Drugs ◽  
United States Government ◽  
Orphan Drug Act ◽  
The Government ◽  
Effective Drugs ◽  
Potential Interactions

To overcome the unattractiveness of small markets, the United States government provides financial aid and incentives for drug manufacturers to create cures for rare diseases under the Orphan Drug Act (“the Act”). Recent research integrating genetic information and pharmacology holds promise for creating more effective drugs targeted at smaller populations than ever before. In the near future, it seems that a flood of new drugs targeted at small disease populations could take advantage of the government benefits under the Act. Drug applicants will include true orphan drugs along with “Trojan” applicants that seek to co-opt the benefits for drugs that should not qualify as orphans. Currently, the FDA appears ill prepared to discern between the two types of applicants and prevent abuse of the system.In 1983, the federal government passed the Act. Congress designed the Act and subsequent modifications to provide incentives for companies to bring drugs for rare diseases to market.

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