Thanks Glenn - to add also, it is the most fundamentally important ditty in this entire scam. If it was an aircraft developed 10 times faster than ever before, and it crashed due to defects in manufacture, accident investigators would be all over the manufacturing sites and the people working there, identifying all the shortcuts that must have taken place. Even now, people aren’t asking, still believing the ‘myth’ of immaculate conception of drugs!!!
Interesting story that. It is true no medicine can be deemed real, until they are produced in scale, after establishing their safety profile etc. but then the birth pangs of a medicine, in the nature of a new molecule being synthesised or a natural product being recovered and purified etc, is also real, often long - which the public will not know. But Covid when it appeared in early 2020, though a new disease, did not require new molecules ( anti virals). No medical text book says that a new virus can be eliminated only by a new viral. That is how all other possible options of repurposed medicines, backed by related existing research, were stalled to give time to the hurried offer of Paxlovids, Remdesivirs, Molnupiravirs etc, leaving millions of patients to their death beds without any early treatments. Thus the Covid treatment scene was different. Starting 2021, those who clinically understood that old school medicines like Ivermectin, HCQ, Azithromycin, Montelukast, anti histamines and steroidal and non steroid immune modulators etc could defang this virus quickly and effectively, began burying this virus by end 2021. Those who denigrated this approach and bet totally on new, half tested stuff, like vaccines and new anti virals, haven’t yet recovered from the hammering by this virus. As I have often said elsewhere, the 2000 odd active drug molecules we know today from many different streams are multi- capable, can take on most existing and future diseases and the effort needed to identify the best ones among them for a given need are of a different nature. It requires that the new generation of doctors become better clinicians and constantly keep updating themselves.
Spot on. My next book for Wiley to be published in the New Year will be a 300 page text book for graduates and professionals, both inside and outside the industry - it addresses your points here 😁
I would take the liberty of requesting for a complimentary copy of the book, if possible. In India, such books are expensive and individual ownership is rare. In the case of C-19, there was already some experience with repurposed drugs years ago with the first SARS. Even in years preceding Covid, people have looked at a chemical class of drugs called Cationic Amphiphilic Drugs ( CADs), as possible anti virals against RNA viruses, based on their chemistry in cell lysosomes. For example, a 2017 paper from Italy profiles about 25 such drugs from many different indications, as anti virals. In 2020 itself, people quickly began evaluating such drugs successfully based on the premise of CADs. That is how the choice for many doctors zeroed in on drugs like Anti histamines, Azithromycin, Montelukast, HCQ etc ( Ivermectin was different) being additionally anti virals. Fascinated by the chemistry of these, I looked at the chemical structures of over 700 known drug molecules, from over 20 different indications. Based on their nitrogen based chemical structures, a gross shared structural feature, I got the inkling that almost all of them could be additionally anti virals. However, my efforts requesting a few researchers to go for a quick screening did not bear fruit. This led me to believe that most of these drugs will have atleast 2-3 extra potentials. Slowly, reports of repurposing many common drugs for cancer, autoimmune diseases, Alzemeirs, Parkinson’s etc started trickling into my inbox. Now, is the time for repurposing of drugs - on a very big scale. This would change the scenario of drug development and completely eliminate the stranglehold of commercial interests in it. Only for very rare needs, we will need new drugs and that, as in the case of Penicillin, must become the preserve of universities and public funded medical research schools. My gut feeling is that the present portfolio of drugs can be repurposed for over 90% of treatment needs - from simple pains to cancers. They can serve humanity for the next 50 years easily - safely, effectively, affordably, and with easy access everywhere. It is also my earnest desire that repurposed drugs must become a serious subject in medical degrees, even worthy of a post graduate specialisation. That is how the impetus for continuous research and exploration for the subject can be sustained.
This is an article of mine published in GMP Review: https://www.dropbox.com/scl/fi/bwm5kqa3wix9u8z6i71h0/GMP-Vol20No2_Rees.pdf?rlkey=66t72wvndnflcc3rkwn4rhzue&dl=0 if speaks to doctors being able to re-purpose medicines once they understand the chemistry, manufacturing and controls (CMC) aspects. It highlights the lack of manufacturing understanding in drug development, Big pharma companies don't have it any more, but that's what I do. Please do have a read. The book will by $100+ and I have no control over the price. Hopefully you can learn a lot here...
Surely it is playing into Pharma's hands when the focus is on dealing with symptoms rather than causes. Removing the causes of disease is surely the priority not inventing new medicines to deal with the symptoms of the last medicine.
Thanks Hedley. No distinction is drawn by the Papers beyween bacterial and viral infections. We know after ConVid, that the Virus debate is still ongoing. A better study would be directed perhaps at the vast number of vaccine and Pharma harms for which the drugs are "required". After all a Patient Cured is a Customer Lost.
If there is one clinical lesson to be learnt from the successful use of antibiotics like Azithromycin and a few others in covid, it is that the distinction between anti virals and antibiotics, as stand alone categories of drugs, needs to be reviewed. As I explained in another post here on structural chemistry features of common drugs in COVID, some of these anti biotics were chiefly looked at as effective part anti virals in covid. And there was this added advantage of any secondary bacterial infection too getting treated alongside. In many common respiratory infections, the two types might coexist. That also means that a review of the classical stand that “no antibiotics in viral infections” need to be reviewed, in the context of the concern of anti biotic resistance of infections. The classical interpretation of anti biotic resistance itself has to be relooked into. That theory requires the need for totally new antibiotics, not a very patient friendly situation.
Absolutely - a new paradigm is required, based on the principles in the penicillin example - it could have got to market in 4 years if all the skills were assembled from the beginning, instead of 15+ years…
This may not be immediately related to this headline, but I have interacted with a couple of well known physicians cum researchers on the topic of anti biotic resistance, could be another context for repurposed medicines. If a set of known antibiotics have not been found effective against a microbe, the premise now is that those antibiotics are failing, have to look for new anti biotics. This puts a generation of patients to suffering without good clinical treatments. My premise is that those erstwhile established drugs have not failed, but are now inadequate as the microbe has gained some edge over them and this edge needs to be closed with an additional drug related to the condition - could be another anti biotic or even a non anti infective like Ivermectin or any other. Like any other medicinal practice, this will eventually be an accumulated experience to be shared by the community world over. As research and practice on the multiple role of common drugs expand, good, safe options for this approach too will expand. This will enable the tried and tested drugs to be in continuing service. I do hope that many doctors and practitioners following your Substack will be prompted to take note. Kindly discuss this paradigm, bolstering the effect of an existing drug with an add on active molecule, with people whom you interact with in many fora. My wish is that this becomes a text book chapter sometime.
This is music to my ears, Moro (is that your name?). Honest clinicians have been pushed out of the development of new therapies for patients during four decades of blockbuster drugs. The research focus now is molecular modelling software to find ‘hits’ - potential development candidates. They have to be patented, so the 20 year patent clock starts ticking. A chosen candidate is in a race against the clock. All the developing company has is a theory on mechanism of action. As you know, for Alzheimer’s as an example, the MOA is linked to amyloid beta. Thirty late-stage failures in the last 20 years says it’s not that. This magic world of mMRA technology has resurrected new potentially lucrative markets…but it’s all a horrible scam. The failures are down to rushing development candidates into the clinic to collect clinical data as quickly as possible….and the quicker it has got, the more the failure rates has ballooned. The first stage of the new paradigm is to go back five decades, where patents were awarded for the manufacturing process, such as with penicillin and cimetidine (Tagamet). Then, we educate clinicians on how to establish safe manufacturing supply chains for repurposing compounds such as IVM, where there is significant real-world data of efficacy in a number of important areas.
I understand that ( in USA ?), companies can take patent on the repurposed indication of a drug, but I don’t know if this applies only to the original patent holding company of the drug. Is this for lesser number of years too ? I think 80% of the drug market is for off patent drugs and many even 2-3 decades earlier. Perhaps repurposing a drug still under patent protection might not be straightforward. Otherwise, it is not a problem and we saw it in Covid. If someone wants to evaluate Cetrizine for Alzemeirs on some reported science basis, there shouldn’t be a problem. In fact, repurposing has to be hotly and seriously researched for conditions like cancer, Alzemeirs, Parkinson’s, many Autoimmune diseases and the like where single theories imposed by vested interests like big Pharma have strangled the patients with back breaking costs, frequent failures of new drugs in bulk use etc, denying them with other treatment options that can be cheap, safe and more effective. Even in more freely practising countries, the grip of the big Pharma in these diseases still prevails. Of course, it is worse in countries like the USA with tightly leashed systems. Repurposing drugs is a huge, huge subject, lot of studies and research is needed, often with live testing, but individual doctors can begin building their own small domain of expertise with available knowledge and experience and as part of their regular practice. They must have the commitment to share their experience freely with the rest of the world. They must also realise that they will stand to gain with more patients enrolment for them, compared to another one.
Incidentally, I remember seeing a paper of 2021 ( lost the reference) where software modelling of the existing drug basket identified something like 1500 odd hits for Covid. Around that time, I had made my chemistry based back of the envelope estimate of possible anti virals from the existing portfolio of about 2500 active molecules. I have read that 80% of them have Nitrogen in their chemical structures. If 80% of these have that Nitrogen in an amine like/ basic situation ( pKa above 7.5), which was my premise for anti viral properties, my hits would be 80% of 80% of 2500 active molecules - 1600 of them. Obviously, this has to be from every possible indication - from expensive cancer drugs to OTC pain killers. Talking of the latter, a 2020 study in India found Indomethacin to work effectively in the viral phase in Covid, easing up hospitalised patients.
I will make it as a main comment here in the context of the conversations we had below. I have seen your paper as well and I have a slightly different take on what everyday doctors should know with reference to prescribing repurposed drugs. More important than points like GMP, supply chain etc, assuming even a common GP would strive to self specialise a few chosen indications of interest to him, he is must have a complete idea of the commonly used drug molecules of those indications. This should include a bit of their organic chemistry, their active chemical sites (in their structures), their known metabolism, the biological course of the diseases for which those drugs are used etc. All that is needed is some painstaking preparation of some permanent notes - preferably a hand written manual, about 2 pages for each of the 100 drugs you may dig into for his prescription needs. I have 200 pages of hand written chemical structures of about 700 drugs which I regularly glance into, as my inspiration. . From the Internet and other reading sources, they should also collect information on which other diseases that would pair ( partially or fully) with the metabolism of the drugs, for which they could be eventually repurposed. They should prepare notes on these and keep for constant reading and consultation. If they develop a flair for such enquiries, they will automatically become experts in time. Most of the time , they need not be the first one or a pioneer, lot of published or reported work would be available, nowadays easily accessible from internet. Yes, serendipity has its small role in clinical medicine, but most of the time, it is organised reading and other forms of exposure to the existing knowledge and experience that matters. Unlike most other professions, for a doctor there is no last thing that he has known. Seeking knowledge, information, awareness, experience is a life long pursuit for them. In places like the USA, the medicinal system itself is a big constraint on expanding the scope of treatments with repurposed medicines. Like the need for a generic drug supplier to have applied for a repurposing approval, before a doctor can prescribe it for the condition. What for ? What is the problem if the doctor wants a small course of Levocetrizine for a Covid positive tested patient, if he is experiencing only nasal symptoms. Theoretically, a new virus is also a new allergen to the patient, eminently treatable with an anti histamine. The system there prevents some interested every day doctors in becoming expert clinicians based on their professional experience. In many lesser countries, it is all more open, with the doctors having a freer hand. This is the biggest hurdle ( one among a few more) for the science and practice of repurposed medicines to flourish in places like the USA.
Great little ditty, Hedley! Every time I turn a corner, my belief in the world I once knew, changes by one more degree.
So glad to be awake though, and not a woke!
Thanks Glenn - to add also, it is the most fundamentally important ditty in this entire scam. If it was an aircraft developed 10 times faster than ever before, and it crashed due to defects in manufacture, accident investigators would be all over the manufacturing sites and the people working there, identifying all the shortcuts that must have taken place. Even now, people aren’t asking, still believing the ‘myth’ of immaculate conception of drugs!!!
Interesting story that. It is true no medicine can be deemed real, until they are produced in scale, after establishing their safety profile etc. but then the birth pangs of a medicine, in the nature of a new molecule being synthesised or a natural product being recovered and purified etc, is also real, often long - which the public will not know. But Covid when it appeared in early 2020, though a new disease, did not require new molecules ( anti virals). No medical text book says that a new virus can be eliminated only by a new viral. That is how all other possible options of repurposed medicines, backed by related existing research, were stalled to give time to the hurried offer of Paxlovids, Remdesivirs, Molnupiravirs etc, leaving millions of patients to their death beds without any early treatments. Thus the Covid treatment scene was different. Starting 2021, those who clinically understood that old school medicines like Ivermectin, HCQ, Azithromycin, Montelukast, anti histamines and steroidal and non steroid immune modulators etc could defang this virus quickly and effectively, began burying this virus by end 2021. Those who denigrated this approach and bet totally on new, half tested stuff, like vaccines and new anti virals, haven’t yet recovered from the hammering by this virus. As I have often said elsewhere, the 2000 odd active drug molecules we know today from many different streams are multi- capable, can take on most existing and future diseases and the effort needed to identify the best ones among them for a given need are of a different nature. It requires that the new generation of doctors become better clinicians and constantly keep updating themselves.
Spot on. My next book for Wiley to be published in the New Year will be a 300 page text book for graduates and professionals, both inside and outside the industry - it addresses your points here 😁
I would take the liberty of requesting for a complimentary copy of the book, if possible. In India, such books are expensive and individual ownership is rare. In the case of C-19, there was already some experience with repurposed drugs years ago with the first SARS. Even in years preceding Covid, people have looked at a chemical class of drugs called Cationic Amphiphilic Drugs ( CADs), as possible anti virals against RNA viruses, based on their chemistry in cell lysosomes. For example, a 2017 paper from Italy profiles about 25 such drugs from many different indications, as anti virals. In 2020 itself, people quickly began evaluating such drugs successfully based on the premise of CADs. That is how the choice for many doctors zeroed in on drugs like Anti histamines, Azithromycin, Montelukast, HCQ etc ( Ivermectin was different) being additionally anti virals. Fascinated by the chemistry of these, I looked at the chemical structures of over 700 known drug molecules, from over 20 different indications. Based on their nitrogen based chemical structures, a gross shared structural feature, I got the inkling that almost all of them could be additionally anti virals. However, my efforts requesting a few researchers to go for a quick screening did not bear fruit. This led me to believe that most of these drugs will have atleast 2-3 extra potentials. Slowly, reports of repurposing many common drugs for cancer, autoimmune diseases, Alzemeirs, Parkinson’s etc started trickling into my inbox. Now, is the time for repurposing of drugs - on a very big scale. This would change the scenario of drug development and completely eliminate the stranglehold of commercial interests in it. Only for very rare needs, we will need new drugs and that, as in the case of Penicillin, must become the preserve of universities and public funded medical research schools. My gut feeling is that the present portfolio of drugs can be repurposed for over 90% of treatment needs - from simple pains to cancers. They can serve humanity for the next 50 years easily - safely, effectively, affordably, and with easy access everywhere. It is also my earnest desire that repurposed drugs must become a serious subject in medical degrees, even worthy of a post graduate specialisation. That is how the impetus for continuous research and exploration for the subject can be sustained.
This is an article of mine published in GMP Review: https://www.dropbox.com/scl/fi/bwm5kqa3wix9u8z6i71h0/GMP-Vol20No2_Rees.pdf?rlkey=66t72wvndnflcc3rkwn4rhzue&dl=0 if speaks to doctors being able to re-purpose medicines once they understand the chemistry, manufacturing and controls (CMC) aspects. It highlights the lack of manufacturing understanding in drug development, Big pharma companies don't have it any more, but that's what I do. Please do have a read. The book will by $100+ and I have no control over the price. Hopefully you can learn a lot here...
Surely it is playing into Pharma's hands when the focus is on dealing with symptoms rather than causes. Removing the causes of disease is surely the priority not inventing new medicines to deal with the symptoms of the last medicine.
Thanks Hedley. No distinction is drawn by the Papers beyween bacterial and viral infections. We know after ConVid, that the Virus debate is still ongoing. A better study would be directed perhaps at the vast number of vaccine and Pharma harms for which the drugs are "required". After all a Patient Cured is a Customer Lost.
Patenting molecular compounds is a nonsense, Jas - the solution is to make them prove they have a viable drug before awarding a patent
If there is one clinical lesson to be learnt from the successful use of antibiotics like Azithromycin and a few others in covid, it is that the distinction between anti virals and antibiotics, as stand alone categories of drugs, needs to be reviewed. As I explained in another post here on structural chemistry features of common drugs in COVID, some of these anti biotics were chiefly looked at as effective part anti virals in covid. And there was this added advantage of any secondary bacterial infection too getting treated alongside. In many common respiratory infections, the two types might coexist. That also means that a review of the classical stand that “no antibiotics in viral infections” need to be reviewed, in the context of the concern of anti biotic resistance of infections. The classical interpretation of anti biotic resistance itself has to be relooked into. That theory requires the need for totally new antibiotics, not a very patient friendly situation.
Absolutely - a new paradigm is required, based on the principles in the penicillin example - it could have got to market in 4 years if all the skills were assembled from the beginning, instead of 15+ years…
This may not be immediately related to this headline, but I have interacted with a couple of well known physicians cum researchers on the topic of anti biotic resistance, could be another context for repurposed medicines. If a set of known antibiotics have not been found effective against a microbe, the premise now is that those antibiotics are failing, have to look for new anti biotics. This puts a generation of patients to suffering without good clinical treatments. My premise is that those erstwhile established drugs have not failed, but are now inadequate as the microbe has gained some edge over them and this edge needs to be closed with an additional drug related to the condition - could be another anti biotic or even a non anti infective like Ivermectin or any other. Like any other medicinal practice, this will eventually be an accumulated experience to be shared by the community world over. As research and practice on the multiple role of common drugs expand, good, safe options for this approach too will expand. This will enable the tried and tested drugs to be in continuing service. I do hope that many doctors and practitioners following your Substack will be prompted to take note. Kindly discuss this paradigm, bolstering the effect of an existing drug with an add on active molecule, with people whom you interact with in many fora. My wish is that this becomes a text book chapter sometime.
This is music to my ears, Moro (is that your name?). Honest clinicians have been pushed out of the development of new therapies for patients during four decades of blockbuster drugs. The research focus now is molecular modelling software to find ‘hits’ - potential development candidates. They have to be patented, so the 20 year patent clock starts ticking. A chosen candidate is in a race against the clock. All the developing company has is a theory on mechanism of action. As you know, for Alzheimer’s as an example, the MOA is linked to amyloid beta. Thirty late-stage failures in the last 20 years says it’s not that. This magic world of mMRA technology has resurrected new potentially lucrative markets…but it’s all a horrible scam. The failures are down to rushing development candidates into the clinic to collect clinical data as quickly as possible….and the quicker it has got, the more the failure rates has ballooned. The first stage of the new paradigm is to go back five decades, where patents were awarded for the manufacturing process, such as with penicillin and cimetidine (Tagamet). Then, we educate clinicians on how to establish safe manufacturing supply chains for repurposing compounds such as IVM, where there is significant real-world data of efficacy in a number of important areas.
I understand that ( in USA ?), companies can take patent on the repurposed indication of a drug, but I don’t know if this applies only to the original patent holding company of the drug. Is this for lesser number of years too ? I think 80% of the drug market is for off patent drugs and many even 2-3 decades earlier. Perhaps repurposing a drug still under patent protection might not be straightforward. Otherwise, it is not a problem and we saw it in Covid. If someone wants to evaluate Cetrizine for Alzemeirs on some reported science basis, there shouldn’t be a problem. In fact, repurposing has to be hotly and seriously researched for conditions like cancer, Alzemeirs, Parkinson’s, many Autoimmune diseases and the like where single theories imposed by vested interests like big Pharma have strangled the patients with back breaking costs, frequent failures of new drugs in bulk use etc, denying them with other treatment options that can be cheap, safe and more effective. Even in more freely practising countries, the grip of the big Pharma in these diseases still prevails. Of course, it is worse in countries like the USA with tightly leashed systems. Repurposing drugs is a huge, huge subject, lot of studies and research is needed, often with live testing, but individual doctors can begin building their own small domain of expertise with available knowledge and experience and as part of their regular practice. They must have the commitment to share their experience freely with the rest of the world. They must also realise that they will stand to gain with more patients enrolment for them, compared to another one.
Incidentally, I remember seeing a paper of 2021 ( lost the reference) where software modelling of the existing drug basket identified something like 1500 odd hits for Covid. Around that time, I had made my chemistry based back of the envelope estimate of possible anti virals from the existing portfolio of about 2500 active molecules. I have read that 80% of them have Nitrogen in their chemical structures. If 80% of these have that Nitrogen in an amine like/ basic situation ( pKa above 7.5), which was my premise for anti viral properties, my hits would be 80% of 80% of 2500 active molecules - 1600 of them. Obviously, this has to be from every possible indication - from expensive cancer drugs to OTC pain killers. Talking of the latter, a 2020 study in India found Indomethacin to work effectively in the viral phase in Covid, easing up hospitalised patients.
I will make it as a main comment here in the context of the conversations we had below. I have seen your paper as well and I have a slightly different take on what everyday doctors should know with reference to prescribing repurposed drugs. More important than points like GMP, supply chain etc, assuming even a common GP would strive to self specialise a few chosen indications of interest to him, he is must have a complete idea of the commonly used drug molecules of those indications. This should include a bit of their organic chemistry, their active chemical sites (in their structures), their known metabolism, the biological course of the diseases for which those drugs are used etc. All that is needed is some painstaking preparation of some permanent notes - preferably a hand written manual, about 2 pages for each of the 100 drugs you may dig into for his prescription needs. I have 200 pages of hand written chemical structures of about 700 drugs which I regularly glance into, as my inspiration. . From the Internet and other reading sources, they should also collect information on which other diseases that would pair ( partially or fully) with the metabolism of the drugs, for which they could be eventually repurposed. They should prepare notes on these and keep for constant reading and consultation. If they develop a flair for such enquiries, they will automatically become experts in time. Most of the time , they need not be the first one or a pioneer, lot of published or reported work would be available, nowadays easily accessible from internet. Yes, serendipity has its small role in clinical medicine, but most of the time, it is organised reading and other forms of exposure to the existing knowledge and experience that matters. Unlike most other professions, for a doctor there is no last thing that he has known. Seeking knowledge, information, awareness, experience is a life long pursuit for them. In places like the USA, the medicinal system itself is a big constraint on expanding the scope of treatments with repurposed medicines. Like the need for a generic drug supplier to have applied for a repurposing approval, before a doctor can prescribe it for the condition. What for ? What is the problem if the doctor wants a small course of Levocetrizine for a Covid positive tested patient, if he is experiencing only nasal symptoms. Theoretically, a new virus is also a new allergen to the patient, eminently treatable with an anti histamine. The system there prevents some interested every day doctors in becoming expert clinicians based on their professional experience. In many lesser countries, it is all more open, with the doctors having a freer hand. This is the biggest hurdle ( one among a few more) for the science and practice of repurposed medicines to flourish in places like the USA.
Will respond tomorrow- appreciate your wise words 😁
Thank you for sharing the truth!🙏🏻
Much more to come Henry - thank you so much!!!