- \n
- Gov Lists 28 Clinical Studies, Mostly Ocular, for Aptamers<\/strong><\/li>\n
- Only 3 On This List Are Currently Active Studies<\/strong><\/li>\n
- NOXXON Pharma\u2019s Mirror-Image L-RNA Aptamer is in the Clinic for Cancers<\/strong><\/li>\n<\/ul>\n
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Devoted readers of\u00a0Zone In With Zon<\/em>\u00a0who have photographic memories\u2014or anyone who simply uses this blog\u2019s search engine\u2014will know that my\u00a0first blog<\/a>\u00a0on aptamers touted these nucleic acids as being better than antibodies in many applications. That deliberately provocative proclamation was followed by a\u00a0second blog<\/a>\u00a0on aptamers featuring top-cited publications, and also included aptamer studies which cited TriLink products in the methods section. The present, third blog on aptamers focuses entirely on clinical applications.<\/p>\n
In the interest of full disclosure, picking this blog\u2019s titled topic was catalyzed, so to speak, by my being invited to contribute a chapter devoted to clinical aspects of aptamers for a book on nucleic acids therapeutics to be published in 2019. After this book becomes available, I\u2019ll be able to comment on its well-known co-editors, many contributors, and comprehensive contents. However, for now, here are \u201csneak previews\u201d of some items that will be covered in my chapter.<\/p>\n
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Overview of Aptamer Functional Versatility<\/strong><\/p>\n
![\"\"](\"http:\/\/zon.trilinkbiotech.com\/wp-content\/uploads\/2018\/02\/aptamer-300x242.png\")
<\/p>\nTaken from\u00a0genelink.com<\/a><\/p>\n<\/div>\n
Aptamers are highly structured nucleic acids that bind to a specific target molecule. RNA or DNA aptamers are usually selected from a very large pool (aka library) of random sequences, and can be comprised of either natural and\/or chemically modified nucleotides. Clinical applications of aptamers, with or without chemical modifications, are all predicated on target-specific binding.<\/p>\n
However, as depicted below for diverse examples, aptamers can function as therapeutic agents\u00a0per se<\/em>, or as targeting agents. Direct agency of an aptamer drug can include binding to either extracellular protein, cell-surface protein, or viral surface protein, wherein each target is associated with a specific disease or clinical indication of interest for achieving therapeutic intervention. These three targets are also addressable by conventional small molecules or antibodies; however, it was recognized early on that aptamers might provide advantages in specificity or cost, respectively.<\/p>\n
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![\"\"](\"http:\/\/zon.trilinkbiotech.com\/wp-content\/uploads\/2018\/02\/therapeutic.png\")
<\/p>\nCartoon depicting various modes for RNA aptamers (shown as stem-loop structures) functioning as therapeutic agents (left panel) or as cell-targeting agents (right panel). Figure from Poolsup & Kim with permission.<\/p>\n<\/div>\n
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Use of aptamers as targeting agents is depicted as conjugates for delivery of either a nanoparticle loaded with drug, therapeutic oligonucleotide, such as short-interfering RNA (siRNA), or small molecule drug, such as a cytotoxic agent. Although the present blog is devoted to the first modality, namely, aptamers as therapeutic (i.e. clinical) agents, a review by\u00a0Poolsup & Kim<\/a>\u00a0can be consulted for information on the second mode, namely, aptamers as targeting agents.<\/p>\n
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Aptamer Drugs Listed in ClinicalTrials.Gov<\/strong><\/p>\n
ClinicalTrials.gov<\/a>\u00a0is my \u201cgo to\u201d website for obtaining reliable information on clinical investigations in general. This freely accessible website is a comprehensive registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. This trove of information, which is provided as a service of the U.S. National Institutes of Health, is currently comprised of 261,814 clinical research studies in all 50 states and in 201 countries.<\/p>\n
Basic information for each study listed in ClinicalTrials.gov includes the sponsor, participating investigators and hospitals, aptamer drug, targeted disease(s), and type of study (aka\u00a0Phase<\/a>), i.e. safety (Phase 1), efficacy (Phase 2), and better than standard of care (Phase 3). Geographical mapping on global, country, or state\/regional bases for participating hospitals is also provided.<\/p>\n
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![\"\"](\"http:\/\/zon.trilinkbiotech.com\/wp-content\/uploads\/2018\/02\/clinical.png\")
<\/p>\nTaken from aidsinfo.nih.gov<\/p>\n<\/div>\n
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The ClinicalTrials.gov website is relatively easy to navigate, and has built-in help \u201cbuttons\u201d as well as dropdown menus as aids to find and filter the extensive amount of available information. My search\u00a0results<\/a>\u00a0from ClinicalTrials.gov several months ago using the term \u201captamer\u201d provided information for 32 different clinical studies, which when sorted by medical conditions gave 87 items covering a wide range of diseases, with ocular being the most prevalent general category. However, my reading of procedural details for all 32 studies revealed that, in 4 studies, samples from subjects treated with non-aptamer drugs were to be used for\u00a0in vitro<\/em>\u00a0investigations such as screening for aptamer biomarkers. The remaining 28 clinical studies involve aptamer drugs\u00a0per se<\/em>, about which I\u2019ll comment below.<\/p>\n
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Status of Aptamer Studies in ClinicalTrials.Gov<\/strong><\/p>\n
Among the various ways the search\u00a0results<\/a>\u00a0for 28 aptamer drug studies in ClinicalTrials.gov can be sorted for perusal and commentary, I chose to use study \u201cstatus,\u201d which ClinicalTrials.gov defines as follows:<\/p>\n
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- Completed<\/strong>\u2014clinical study has ended normally, and participants are no longer being examined or treated (that is, the \u201clast subject, last visit\u201d has occurred).<\/li>\n
- Terminated<\/strong>\u2014clinical study has stopped recruiting or enrolling participants early and will not start again and participants are no longer being examined or treated.<\/li>\n
- Withdrawn<\/strong>\u2014clinical study stopped before enrolling its first participant.<\/li>\n
- Active<\/strong>\u2014clinical study is ongoing (that is, participants are receiving an intervention or being examined), but potential participants may not be being currently recruited.<\/li>\n<\/ul>\n
![\"\"](\"http:\/\/zon.trilinkbiotech.com\/wp-content\/uploads\/2018\/02\/macular-268x300.png\")
<\/p>\nTaken from\u00a0doctorabidi.com<\/a><\/p>\n<\/div>\n
These categories can be used as filters to easily group studies for perusal, which when I did so, led to several general observations. The overwhelming majority of the 17 Completed clinical studies involve\u00a0ocular diseases<\/a>, of which\u00a0age-related macular degeneration<\/a>\u00a0(ARMD) was a frequently studied indication. ARMD is the leading cause of blindness for people over the age of 55 years, in the U.S. and Europe, and occurs as either \u201cdry\u201d or \u201cwet\u201d ARMD, as described elsewhere.<\/p>\n
While ARMD is a significant medical problem, my guess as to why it was chosen for initial clinical studies with aptamers is that clinical development had fewer practical challenges. Ocular administration required much smaller amounts of drug, which made manufacturing scale-up less problematic, and there were likely less toxicity issues to worry about. In any case, the sponsors included Eyetech Pharma, Ophthotech Corp, Achemix and NOXXON.<\/p>\n
Terminated or Withdrawn studies, which numbered 8, were also mostly ARMD-related but also included aptamer for hemophilia and acute myeloid leukemia sponsored by Baxalta and Antisoma Research. Perhaps most important are the Active studies, which were only 3 in number, and I\u2019ve put into tabular form here with some basic information including the National Clinical Trials (NCT) identification number that is searchable in any search engine. You can click on each NCT number to access detailed information provided in ClinTrials.gov; however, following are some snippets for each of these Active Studies.<\/p>\n
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Table of Active Studies Listed in ClinicalTrials.Gov in 2017<\/strong><\/p>\n
- Terminated<\/strong>\u2014clinical study has stopped recruiting or enrolling participants early and will not start again and participants are no longer being examined or treated.<\/li>\n
- Only 3 On This List Are Currently Active Studies<\/strong><\/li>\n
![\"\"](\"http:\/\/zon.trilinkbiotech.com\/wp-content\/uploads\/2018\/02\/40-150x150.png\")
<\/p>\n![\"\"](\"http:\/\/zon.trilinkbiotech.com\/wp-content\/uploads\/2018\/02\/pubs.jpg\")
<\/p>\n![\"\"](\"http:\/\/zon.trilinkbiotech.com\/wp-content\/uploads\/2018\/02\/iomers-300x273.png\")
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