Article
Pharmacology & Pharmacy
Sibren van den Berg, Saco de Visser, Hubert G. M. Leufkens, Carla E. M. Hollak
Summary: The European Commission emphasizes the role of academic researchers in drug repurposing, and this study summarizes the contributions of academia to registered repurposed orphan medicinal products over the last 5 years. While the majority of repurposed OMPs originate from academia, there is a gap between healthcare professionals, regulators and industry. Potential solutions include improved regulatory and reimbursement knowledge by academia and the right for regulators to integrate new effectiveness data into product labels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Noa Rosenberg, Sibren van den Berg, Nina N. Stolwijk, Bart A. W. Jacobs, Hendrika C. Post, Anna M. G. Pasmooij, Saco J. de Visser, Carla E. M. Hollak
Summary: This paper provides an easily applicable roadmap for academic researchers to make rare disease medicines available for patients. It emphasizes the importance of interaction with regulators and highlights alternative routes for timely access to medicines. Aligning academic studies with regulatory and reimbursement requirements is crucial for improving access to rare disease medicines.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Siddhee A. Sahasrabudhe, Marcia R. Terluk, Reena V. Kartha
Summary: N-acetylcysteine (NAC) acts as an antioxidant through various mechanisms and has a long history of use as a prescription and off-label over-the-counter product. However, systematic clinical pharmacology investigations on NAC are limited. This review focuses on exploring the use of NAC in rare diseases targeting mitochondrial dysfunction and discusses its history, approved indications, mechanisms of action, safety, and pharmacokinetics, as well as ongoing research on NAC derivatives.
Article
Pharmacology & Pharmacy
Pierre Etienne Chazal, Segolene Ayme
Summary: A timely diagnosis is crucial for proper clinical management, but diagnosing rare diseases presents challenges due to their diversity and quantity. Digital technologies offer new opportunities in improving diagnosis and care for RD, though only applicable to a limited number of diseases. The approach presented aims at defining a subset of priority RD for the development and testing of new solutions to reduce diagnosis time.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemical Research Methods
Seyedeh Shaghayegh Sadeghi, Mohammad Reza Keyvanpour
Summary: Drug repurposing is a crucial function in pharmaceutical fields that focuses on discovering new uses and indications for existing or failed drugs. It is cost-effective and reliable compared to experimental drug discovery processes, and various computational methodologies have been proposed for large-scale drug repurposing using high throughput data. However, there is a lack of comprehensive analysis in the literature on the current computational drug repurposing methodologies.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Anup P. Challa, Nicole M. Zaleski, Rebecca N. Jerome, Robert R. Lavieri, Jana K. Shirey-Rice, April Barnado, Christopher J. Lindsell, David M. Aronoff, Leslie J. Crofford, Raymond C. Harris, T. Alp Ikizler, Ingrid A. Mayer, Kenneth J. Holroyd, Jill M. Pulley
Summary: Repurposing is an efficient method in drug development for identifying new therapeutic opportunities at reduced cost and time, especially in the realm of rare disease treatment. The selection of drugs to be tested in certain conditions currently involves both human and machine discovery, but balancing the roles of these approaches, including artificial intelligence, remains a significant topic in drug discovery.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Tania Lourenco, Nuno Vale
Summary: Prostate cancer is the second most common cancer in men worldwide and a leading cause of death. Standard treatments face issues like side effects and resistance, highlighting the need for drugs that can fill these gaps. This review compiles drugs that can be repurposed for prostate cancer treatment, categorizing them based on their pharmacotherapeutic groups and discussing their mechanisms of action.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Ahmed Olatunde, Manisha Nigam, Rahul Kunwar Singh, Abhaya Shikhar Panwar, Abdulwahab Lasisi, Fahad A. Alhumaydhi, Vijay Jyoti Kumar, Abhay Prakash Mishra, Javad Sharifi-Rad
Summary: Cancer management often involves chemotherapy, surgery, and radiotherapy, but chemotherapy can be cytotoxic to normal cells and lead to drug resistance. Antidiabetic drugs such as sulfonylureas, biguanides, and thiazolidinediones have shown beneficial effects in cancer treatment, despite potential risks like pancreatic cancer development.
CANCER CELL INTERNATIONAL
(2021)
Review
Pharmacology & Pharmacy
Yu-Jun Huang, Wan-Yu Chao, Chi-Chuan Wang, Lin-Chau Chang
Summary: The USA pioneered orphan drug-specific legislation, which was subsequently followed by other regions such as the EU, Australia, Japan, and Taiwan. This article discusses the regulations and impacts of these regions, which have specific frameworks for orphan drugs. Different scopes of rare diseases or orphan drugs, incentives, and reimbursement systems highlight the prioritization of the agencies involved. The numbers of designated and approved drugs reflect the effect of regulatory and reimbursement frameworks. Comparing these frameworks and their impact can provide valuable information for developing and improving related frameworks in countries worldwide.
DRUG DISCOVERY TODAY
(2022)
Review
Pharmacology & Pharmacy
Julianne H. Tieu, Siddhee A. Sahasrabudhe, Paul J. Orchard, James C. Cloyd, Reena V. Kartha
Summary: X-linked adrenoleukodystrophy (X-ALD) is a rare genetic neurodegenerative disease with limited treatment options. Drug repurposing has been explored to find effective therapies, but none have been approved for use yet. Advanced translational and clinical pharmacological approaches may improve the success of repurposed drugs for X-ALD and other rare diseases.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Catarina Moura, Nuno Vale
Summary: Dopamine is a neurotransmitter that regulates cognitive and emotional processes in the brain. Its role in cancer is uncertain, but it interacts with receptors in tumor cells and influences cellular processes such as proliferation and migration. Drugs developed for other purposes have been explored for potential cancer treatment, but the role of dopamine in this context needs further clarification.
Review
Cell Biology
Cong Huang, Wenting Li, Xuanyao Ren, Mindan Tang, Kaoyuan Zhang, Fan Zhuo, Xia Dou, Bo Yu
Summary: The cGAS-STING signaling pathway plays a crucial role in infection, autoimmunity, and tumor immunity, and its abnormalities are associated with skin diseases and cancers. New therapeutics targeting this pathway are being developed for skin disorder treatment. However, the precise molecular mechanisms of cGAS-STING-mediated cutaneous disorders have not been fully understood. This review summarizes the regulatory roles and mechanisms of cGAS-STING signaling in skin disorders and provides an update on cGAS-STING-related drug development and potential clinical applications.
Review
Biotechnology & Applied Microbiology
Ruijun Cai, Ling Zhang, Hao Chi
Summary: The eye is a complex organ with various anatomical barriers and clearance mechanisms, necessitating the development of a secure and efficient ocular medication delivery system. Advances in polymer-based nanomicelles have allowed for sustained medication retention and enhanced permeation within the eye, making them the forefront technology in ocular medication. This review consolidates ocular medications based on polymer nanomicelles from 2014 to 2023 and discusses the challenges they pose in clinical applications, providing insights for future clinical research in ocular medication delivery formulations.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
News Item
Multidisciplinary Sciences
Sara Reardon
Summary: The World Health Organization's disease reports indicate public-health priorities and surveillance capabilities.
Letter
Medicine, Research & Experimental
David Lapidus
Summary: The recent paper by Kariampuzha et al. presents an exciting application of artificial intelligence in rare disease epidemiology, surpassing Orphanet in terms of providing basic epidemiological data on rare diseases. However, the AI tool currently lacks key information found in full-text articles, and its public version differs from the original article. Therefore, it should be used similar to Orphanet, with manual verification for completeness and accuracy. Users need to understand that the AI tool is not a cure-all solution for analyzing rare disease epidemiology.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Economics
Benjamin N. Rome, Alexander C. Egilman, Neeraj G. Patel, Aaron S. Kesselheim
Summary: Brand-name drug manufacturers can market or license authorized generics (AGs), which are the same product sold under a generic name. By contrast, independent generics (IGs) are made by other manufacturers. We used this case study to understand how AGs can affect the length of brand-name exclusivity and robustness of generic competition.
Article
Health Care Sciences & Services
Leah Z. Rand, G. J. Melendez-Torres, Aaron S. Kesselheim
Summary: This study analyzed whether other outcome measures used in health technology assessment (HTA) address the criticisms of quality-adjusted life years (QALYs). The study found that among the seven alternative outcome measures currently used for HTA, none of them address all the criticisms of QALYs while retaining their advantageous features.
HEALTH SERVICES RESEARCH
(2023)
Article
Medicine, General & Internal
William B. Feldman, S. Sean Tu, Rasha Alhiary, Aaron S. Kesselheim, Olivier J. Wouters
Summary: This study quantifies and compares the revenue earned on brand-name inhalers approved by the US Food and Drug Administration from 2000 to 2021 before and after the expiration of primary patents on these products.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Editorial Material
Medicine, General & Internal
S. Sean Tu, Sarosh Nagar, Aaron S. Kesselheim
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Letter
Oncology
Edward R. Scheffer Cliff, Gemma Reynolds, Rakesh Popat, Benjamin W. Teh, Aaron S. Kesselheim, Ghulam Rehman Mohyuddin
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Medicine, General & Internal
Cristina Richie, Aaron S. Kesselheim, David S. Jones
Article
Critical Care Medicine
Brandon J. Demkowicz, S. Sean Tu, Aaron S. Kesselheim, Michael A. Carrier, William B. Feldman
Summary: Pharmaceutical companies rely on device patents to maintain market exclusivity for brand-name inhalers.
Article
Medicine, General & Internal
Hussain S. Lalani, Sarosh Nagar, Ameet Sarpatwari, Rachel E. Barenie, Jerry Avorn, Benjamin N. Rome, Aaron S. Kesselheim
Summary: This retrospective cohort study aimed to estimate US public investment in the development of mRNA covid-19 vaccines. The study analyzed publicly funded science from January 1985 to March 2022 and identified 34 NIH-funded research grants directly related to mRNA covid-19 vaccines. The total US public investment in research, development, production, and purchase of mRNA covid-19 vaccines was at least $31.9bn.
BMJ-BRITISH MEDICAL JOURNAL
(2023)
Review
Medicine, General & Internal
Beatrice L. Brown, Aaron S. Kesselheim, Ameet Sarpatwari
Summary: In this analysis, the authors, Ameet Sarpatwari, Beatrice Brown, and Aaron Kesselheim, examine the differences in primary and secondary prevention measures for teratogenic drugs.
Article
Medicine, General & Internal
Catherine S. Hwang, Aaron S. Kesselheim, Ameet Sarpatwari, Krista F. Huybrechts, Gregory Brill, Benjamin N. Rome
Summary: This study estimated the impact of the COVID-19 pandemic and regulatory changes on abortion rates. The findings showed a decrease in the incidence rate of procedural abortions during the pandemic, and this lower rate persisted even after other elective procedures returned to pre-pandemic levels. The use of telehealth for insurance-covered medical abortions remained rare despite the removal of the in-person dispensing requirement for mifepristone.
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Medicine, General & Internal
William B. Feldman, Aaron S. Kesselheim, Jerry Avorn, Massimiliano Russo, Shirley V. Wang
Summary: In 2019, the FDA approved the first generic maintenance inhaler for asthma and COPD. The study compared the effectiveness and safety of the generic inhaler (Wixela Inhub) and the brand-name inhaler (Advair Diskus) in routine care for patients with COPD. The results showed that both inhalers had similar outcomes in terms of COPD exacerbation and pneumonia hospitalization.
ANNALS OF INTERNAL MEDICINE
(2023)
Review
Medicine, General & Internal
Kerstin N. Vokinger, Miquel Serra-Burriel, Camille E. G. Glaus, Ulrich-Peter Rohr, Thomas J. Hwang, Simon Dalla Torre di Sanguinetto, Aaron S. Kesselheim
Summary: The research assessed the regulatory review duration of drug regulatory agencies in the United States and Europe, and found that the review duration in Europe is generally longer than in the United States and Switzerland. The study also revealed that the European Medicines Agency took longer than the U.S. Food and Drug Administration to review drugs, and there were differences in submission times between the United States and Europe.
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Medicine, General & Internal
John C. Messinger, Leo Beletsky, Aaron S. Kesselheim, Rachel E. Barenie
Summary: Naloxone plays a crucial role in preventing death from opioid overdose, but its accessibility remains limited. The recent approval of an over-the-counter formulation of naloxone provides an important opportunity to increase distribution, but careful steps must be taken to ensure it doesn't hinder overall access. This includes ensuring a sustainable supply at affordable prices, prioritizing comprehensive distribution methods, and investing in harm-reduction strategies such as supervised consumption spaces.
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Medicine, General & Internal
Liam Bendicksen, Diana M. Zuckerman, Jerry Avorn, Sophia Phillips, Aaron S. Kesselheim
Summary: The FDA approved eteplirsen for Duchenne muscular dystrophy in 2016 based on a study of 12 boys. The approval has been controversial due to questionable evidence, delays in testing, and high prices. Questions about effectiveness and safety remain, and further reforms are needed to balance evidence generation with patient safety.
ANNALS OF INTERNAL MEDICINE
(2023)
Editorial Material
Pharmacology & Pharmacy
S. Sean Tu, Aaron S. Kesselheim
Summary: This article discusses the barriers that patents create for generic drug entry and introduces the "skinny label" pathway created by Congress to address this issue. The recent court case has put this pathway at risk.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)