Coronavirus - GS-441524 a promising Covid-19 Treatment stalled - will Gilead and the FDA help Texas University cancer researchers find out the truth ?

Jul 2, 2020
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In May 2020 Cancer researchers from the University of Texas set out in some detail why Gileads drug GS-441524 was superior to Gileads Remdesivir as a Coronavirus treatment. This was based both on animals trials and previous research on GS-441524. In some animals trials GS-441524 was compared directly with Remdesivir, as an anti coronavirus treatment, with GS-441524 becoming the preferred treatment.

Gilead developed Remdesivir with the FDA, however it is much more complicated and expensive to make than GS-441524 and could be less effective but for numerous reasons Gilead will make more money from Remdesivir and the FDA may also has a financial interest in remdesivir.

Critics say a long known promising Covid-19 treatment GS-441524 has not been studied and that it was delibrately blocked, for profit reasons, from Covid-19 researchers, having proper access to all the information on it.

Prior lab studies have shown that GS-441524 is effective against coronaviruses SARS, MERS and FIP a near 100% fatal cat coronavirus that GS-441524 had a near 100% cure rate for.

Gileads' responses have not addressed the points raised nor whether Gilead is promoting remdesivir because of its longer patent or why Gilead blocked and/or also had not encouraged or helped anyone researching the medical effectiveness of GS-441524 to resolve matters.

Gilead has for a some years also refused to explain why it has not allowed the manufacture or licensing of GS-441524 for use in cats after successful animal trials cured cats of a fatal coronavirus disease


A journalist writing in The Atlantic said "After Ebola trials in previous years found little benefit, remdesivir became a drug in search of a (human) disease."

Some years ago GS-441524 and Remdesivir were both tested against FIP a 95% fatal cat coronavirus.

Gilead was involved in these University of California animal tests providing the 25+ different drugs initially screened for use in the trials and credited in the published research.

The trials showed both remdesivir and GS-441524 were effective against FIP however GS-441524 was preferred and cured 100% of the coronavirus infected cats in the university tests. Later field tests on pet cats confirmed GS-441524s effectiveness

Strangely Gilead has refused to allow anyone to make or legally use GS-441524 on cats (or any animals or humans) despite repeated requests related to cats

Thus long before Covid-19 cat owners were forced to buy GS-441524 on the black market to treat their cats and Gilead did nothing nor provided any explaination

Critics say Gilead blocks GS-441524 as it is easier and cheaper to make and so will compete against Remdesivir meaning Gilead will make less money

Following Gileads and the FDAs focus on remdesivir and their failure to enter into meaningful discussions or research on GS-441524, an open letter was written to the FDA and Gilead by a citizens advocacy group asking

why GS-441524 was not being studied as a Covid-19 treatment and

that the FDA and others be encouraged to do research or

to explain why it was not scientifically and medically possible to do so.

The citizens group writing the letter has formally raised medical and other matters over many years, is non political and has been critical of both the Trump administration and the FDA and their response to covid-19 and other citizens rights matters. For example they separately launched legal action against the FDA over what is said to be an unsafe medical device that the FDA failed to withdraw.

The FDA has just responded to the GS-441524 coronavirus research letter saying that they have now

“reviewed the literature and agree that this compound merits further exploration,”

View: https://twitter.com/i/web/status/1297572580853915648


The questions the seem important are

why has it taken so long to start this work,

why did it take a citizens group not doctors or researchers or health officials to get this to happen and

will others also now be encouraged to also do research or will it remain a limited work within the FDA

will Gilead do all it can to help serious researchers resolve if GS-441524 is more effective than remdesivir

does the FDA have a financial interest in remdesivir which is why it favors that drug

Gilead has yet to indicate that it will allow others outside the FDA to view any data it or the FDA holds or encourage third party research.

Research indicates that GS-441524 is less toxic than remdesivir so can be given in higher doses and is much easier to make than remdesivir plus has many other benefits over remdesivir.

Texas University researchers have responded to questions about why GC-441524 is probably superior - see statnews article already linked from May 2020 and the following q&a posted


A private Dr highlighted GS-441524 in Feb 2020 in a Tampa Fl news article.

According to journalists and others Gilead has not responded to requests to clarify its position on allowing GS-441524 for the treatment for cats and seems unwilling to provide any meaningful response to requests for clarification on a range of matters about GS-441524 including encouraging meaningful covid-19 research. Gileads responses have focused on stressing remdesivir benefits or passing comments about any researching of GS-441524

Gilead and the FDA jointly developed the drug Remdesivir however Gilead registered the patent without including any FDA rights though later published research papers clearly list the many government scientists involved


GS-441524 was also developed and patented with other parties and is a very similar drug to remdesivir. The Gilead patent life for Remdesivir is 7+ years longer than the GS-441524 patent and for other reasons the GS-441524 patent may be less profitable for Gilead.

Gilead has prior history of trying to exclude the FDA from participating in patent royalities the FDA contributed to developing.


In a letter to leadership of Gilead Sciences, Inc., the National Institutes of Health, the Food and Drug Administration, and the Biomedical Advanced Research and Development Authority, Public Citizen and two scientists specializing in cancer drug development offer a detailed summary of scientific evidence suggesting that the experimental antiviral drug GS-441524 may be a better drug than the closely-related drug remdesivir to treat COVID-19. The letter asks Gilead and the federal agencies either to work collaboratively to promptly pursue the development of GS-441524 as a treatment for COVID-19 or to publicly explain and provide evidence as to why doing so is not scientifically or medically feasible.

The links to the open letter to Gilead and the FDA and other articles and info are below


Open letter to Gilead and FDA



FDA response

View: https://twitter.com/i/web/status/1297572580853915648


“reviewed the literature and agree that this compound merits further exploration,”

Michael Abrams Phd , health researcher at Public Citizen and lead author of the letter to the FDA states “Such further study of the drug is long overdue, especially given the evidence that GS-441524 may be cheaper and easier to manufacture and more amenable to administration in inhaled or oral forms than remdesivir.”

“We hope that Gilead will respond similarly and commit to working collaboratively with the NIH to study the potential of GS-441524, even if it means the company may reap lower profits than expected from the marketing of remdesivir,” Abrams added.



Research on GS-441524


Lab tests have suggested GS-441524 is active against SARS-CoV-2, and it is apparently similar or superior to the effects of remdesivir at levels that do not cause much toxicity, according to the Anderson researchers, who want to run their own tests. They also maintain the compound is more easily synthesized than remdesivir, so it should be easier to create oral versions and make higher doses.


The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

10 cats were infected with FIP and then treated with GS-441524. All 10 cats recovered.

Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA

Gilead Sciences, Foster City, CA, USA

Accepted 14 April 2018



Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses
Susan Amirian
Julie K.Levy

Public Health & Healthcare Program, Texas Policy Lab, School of Social Sciences, Rice University, Houston, TX, USA

Maddie's Shelter Medicine Program, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA

Accepted 24 March 2020,



The Atlantic

The background to the long term Cat research GS-441524 and the treatment people are using to cure cats of a deadly coronavirus that kills around 95% of infected cats

Around 5 years ago Gilead sent University researchers 25 or 30 molecules, drawn from the large library of drug candidates that pharmaceutical companies typically maintain.

Two of the molecules worked marvelously in cat cells infected with the FIP virus: GS-441524 and GS-5734, the latter of which is now better known as remdesivir.

After Ebola trials found little benefit, remdesivir became a drug in search of a (human) disease.

Both molecules were effective, so Pedersen decided to pursue the simpler one, GS-441524. He then infected 10 cats with FIP and dosed them with GS-441524. All 10 cats recovered.

“We almost fell out of our chairs,” says Weigner.

in a follow-up field trial of 31 pets with naturally acquired FIP, 25 ultimately made it—an unheard-of recovery rate.

Despite the success, Gilead refused to license GS-441524 for use in cats.

While Pedersen was testing GS-441524 in cats, a different virus—a human virus—was raging halfway around the world in West Africa: Ebola. The virus that causes Ebola is not a coronavirus, but remdesivir is unusually broad-acting for an antiviral, and early results against Ebola were promising. So promising, in fact, that the company was eyeing FDA approval of remdesivir in humans.

According to Pedersen, Gilead worried that the cat research could impede the approval process for remdesivir. Because GS-441524 and remdesivir are so similar, any adverse effects uncovered in cats might have to be reported and investigated to guarantee remdesivir’s safety in humans.

Gilead’s caution about generating unnecessary cat data is standard industry practice. “One of the rules in drug development is never perform a test you don’t have to, if the results could be problematic,” says Richard Sachleben, a retired pharma-industry researcher.

(Gilead declined to comment for this story.)




Pharmalot
The U.S. government contributed research to a Gilead remdesivir patent — but didn’t get credit
By Ed Silverman @Pharmalot
May 8, 2020

September 2015 in which Gilead sought a U.S. patent for a using the compound for any number of coronavirus infections. Although the code Gilead assigned to the compound – GS-5734 – does not appear in the body of the application, experts who have reviewed the chemical structure say the compound is remdesivir.

One month later, some of the same Gilead employees whose names appeared on the patent application were listed as co-authors on a Nature research paper – along with numerous government scientists – showing remdesivir, specifically, held promise in fighting Ebola and other coronaviruses. The paper also noted testing was conducted at high-risk security labs run by the federal government.

The role played by the federal government in developing remdesivir to combat coronaviruses has, in fact, involved various grants to universities, as well as contributions from government personnel at such agencies as the U.S. Army Medical Research Institute of Infectious Diseases, according to Knowledge Ecology International, an advocacy group that first disclosed these connections.

But while it remains unclear the extent to which federal funds contributed to the R&D, the patent is of particular interest because it is tangible evidence that government work yielded something of potential financial value to the company. Yet government employees are not listed as inventors, which one expert suggested should be corrected, especially in an era when federally financed research might be leveraged to collect royalties or, arguably, lower the price of medicines.

“In this case, all of these scientists were really working together very intimately on research that led to the molecule,” said Arti Rai, a Duke University law professor who specializes in intellectual property and a former U.S. Patent and Trademark Office official, who is researching remdesivir patents and the role played by the federal government.

“Gilead actually had a huge number of patents on the molecules, but had to do a tremendous amount of work to figure out which variations of the various molecules would work against the biological models the government had. This patent illustrates the essence of why collaboration between the public and private sectors is important, not just in terms of money, such as grants, but resources.”

“What really matters is how much money the government has put into research, but if their names were on there, it would help to make the case there was a lot of in-kind contribution from the government,” she explained. “Right now, if Gilead tried to assert rights (in response to a patent challenge), there would be no way to know there was some government right to a license to the patent.”

Generally, one must play connect the dots to find government assistance. For instance, the National Institutes of Health gave grants to several universities whose researchers worked with Gilead scientists. Their efforts appeared in a 2018 paper in the American Society for Microbiology, which found remdesivir can combat coronaviruses, noted Tahir Amin, who heads the Initiative for Medicines, Access, and Knowledge, an advocacy group that challenged various Gilead patents on hepatitis C medicines.

We asked Gilead, which several months ago sought to add claims to the patent, for comment and will update you accordingly.

Numerous consumer advocates, academics, and lawmakers have argued that prescription drugs invented with taxpayer dollars should be affordable to Americans. Public Citizen estimated that U.S. taxpayers contributed $70.5 million to remdesivir R&D overall.

“Since we’re paying for the research, we shouldn’t expect to be at disadvantage,” said Jamie Love of Knowledge Ecology International. “The argument that you have to have a high price because a company made big investments is harder to justify when there was a large public financing role in the R&D. A high company may say a high price is necessary, but the rationale falls apart when we’re paying for the R&D.”

Gilead has often been at the center of such debates. As noted previously, the drug maker and the federal government filed dueling lawsuits over patents that formed the basis of a best-selling HIV prevention pill called Truvada. The government claims Gilead should pay royalties on its patents, which stemmed, in part, from taxpayer funding, while the company has argued the government patents are invalid.


Feb 2020 news article on GS-441524
By Dr. Joette Giovinco

Dr. Joette Giovinco wrote a press article highlighting GS-441524 in Feb 2020 as a promising Covid-19 treatment




Remdesivir is a promising antiviral drug and works by inhibiting the activity of RNA dependent RNA polymerase (RdRp).

GS-441524 is a feline infectious peritonitis virus (FIPV) inhibitor and a predominant metabolite of Remdesivir that is superior to Remdesivir against COVID-19.

First GS-441524 shows comparable efficacy in cell-based models of primary human lung and cat cells infected with the coronavirus. GS-441524 could strongly inhibit feline infectious peritonitis virus (FIPV), with an EC50of 0.78 μM.

Recent research in coronavirus-infected nonhuman primates demonstrated problems with remdesivir that inadvertently showed the antiviral effectiveness of GS-441524. In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream..... injection of remdesivir in NHP results in GS-441524 being present in serum at concentrations 1000-fold higher than remdesivir throughout a 7-day treatment course (Figure 3b).

Last but not the least, GS-441524 is capable of treating cats suffering from feline infectious peritonitis (FIP) with a 96% cure rate. Importantly, coupled with the robust antiviral activity of GS-441524 against FIP, these data compel further investigations into the therapeutic and prophylactic utility of GS-441524 against SARS-CoV-2.

All in all, GS-441524, a FIPV inhibitor, is a predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19.







GILEAD owns patent rights to GS-441524 (2009) and Remdesivir (2017); The 2009 patent of GS-441524 may be invalid due to prior art: as we have seen in the GILEAD vs MERK trial (which Merk initially won), there is a large amount of prior art in the nucleoside space that may invalidate the GS-441524 patent.


Covid-19 treatnent research drug GC376

A final thought - great research is being done on Covid-19 some of it is below on another drug also tested on cats with FIP. However this drug GC376 was much less successful than GS-441524

The researchers of GC376 are clearly very good and professional

However how is it Covid-19 treatment research can be done on GC376 with cat coronavirus FIP treatment effectiveness being cited as one of the reasons for rapid research, and yet this not happen on GS-441524 when its almost 100% effective against the cat coronavirus FIP and worked well against other coronaviruses plus GS-441524 is potentially better than remdesivir ?

antiviral GC376 out of Kansas State University had previously been tested but only seven out of 20 cats had gone into remission. Those results seemed impressive at the time, but GS-441524 appeared to be even better

"Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1-7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission."


Research on GC376


Published: 27 August 2020

Feline coronavirus drug GC376 inhibits the main protease of SARS-CoV-2 and blocks virus replication


GC376 has been used to successfully treat FIP in cats as its breakdown product, GC373, effectively inhibits the Mpro of FCoV. Analogs of these drugs also inhibited the MERS CoV Mpro and blocked viral replication in cells at an EC50 of 0.5 μM14. Our studies show GC376 and GC373 to be effective inhibitors of SARS-CoV-2 Mpro, in agreement with previous studies showing GC373 and GC376 possess broad specificity against the Mpro of coronaviruses and calciviruses (Supplementary Table 2)10,13,14,22. Clearly, these drugs need to be advanced quickly into human trials for COVID-19. SARS-CoV-2 is the cause of COVID-19 and is a virus with a significant mutation rate23. Also, in some patients the virus has persisted longer than 2 months with some possibility of re-infection24. Vaccines are critically important, but still likely a year or more away as this virus may present vaccine challenges.

There are many clinical trials testing drugs re-purposed from their original indications. Remdesivir, a polymerase inhibitor developed as a treatment for Ebola virus25 had initially been used in compassion cases, and is now FDA approved for emergency use in patients with COVID-19......

 
Last edited:

Gringoz

BANNED
Oct 3, 2020
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In May 2020 Cancer researchers from the University of Texas set out in some detail why Gileads drug GS-441524 was superior to Gileads Remdesivir as a Coronavirus treatment. This was based both on animals trials and previous research on GS-441524. In some animals trials GS-441524 was compared directly with Remdesivir, as an anti coronavirus treatment, with GS-441524 becoming the preferred treatment.

Gilead developed Remdesivir with the FDA, however it is much more complicated and expensive to make than GS-441524 and could be less effective but for numerous reasons Gilead will make more money from Remdesivir and the FDA may also has a financial interest in remdesivir.

Critics say a long known promising Covid-19 treatment GS-441524 has not been studied and that it was delibrately blocked, for profit reasons, from Covid-19 researchers, having proper access to all the information on it.

Prior lab studies have shown that GS-441524 is effective against coronaviruses SARS, MERS and FIP a near 100% fatal cat coronavirus that GS-441524 had a near 100% cure rate for.

Gileads' responses have not addressed the points raised nor whether Gilead is promoting remdesivir because of its longer patent or why Gilead blocked and/or also had not encouraged or helped anyone researching the medical effectiveness of GS-441524 to resolve matters.

Gilead has for a some years also refused to explain why it has not allowed the manufacture or licensing of GS-441524 for use in cats after successful animal trials cured cats of a fatal coronavirus disease


A journalist writing in The Atlantic said "After Ebola trials in previous years found little benefit, remdesivir became a drug in search of a (human) disease."

Some years ago GS-441524 and Remdesivir were both tested against FIP a 95% fatal cat coronavirus.

Gilead was involved in these University of California animal tests providing the 25+ different drugs initially screened for use in the trials and credited in the published research.

The trials showed both remdesivir and GS-441524 were effective against FIP however GS-441524 was preferred and cured 100% of the coronavirus infected cats in the university tests. Later field tests on pet cats confirmed GS-441524s effectiveness

Strangely Gilead has refused to allow anyone to make or legally use GS-441524 on cats (or any animals or humans) despite repeated requests related to cats

Thus long before Covid-19 cat owners were forced to buy GS-441524 on the black market to treat their cats and Gilead did nothing nor provided any explaination

Critics say Gilead blocks GS-441524 as it is easier and cheaper to make and so will compete against Remdesivir meaning Gilead will make less money

Following Gileads and the FDAs focus on remdesivir and their failure to enter into meaningful discussions or research on GS-441524, an open letter was written to the FDA and Gilead by a citizens advocacy group asking

why GS-441524 was not being studied as a Covid-19 treatment and

that the FDA and others be encouraged to do research or

to explain why it was not scientifically and medically possible to do so.

The citizens group writing the letter has formally raised medical and other matters over many years, is non political and has been critical of both the Trump administration and the FDA and their response to covid-19 and other citizens rights matters. For example they separately launched legal action against the FDA over what is said to be an unsafe medical device that the FDA failed to withdraw.

The FDA has just responded to the GS-441524 coronavirus research letter saying that they have now

“reviewed the literature and agree that this compound merits further exploration,”

View: https://twitter.com/i/web/status/1297572580853915648


The questions the seem important are

why has it taken so long to start this work,

why did it take a citizens group not doctors or researchers or health officials to get this to happen and

will others also now be encouraged to also do research or will it remain a limited work within the FDA

will Gilead do all it can to help serious researchers resolve if GS-441524 is more effective than remdesivir

does the FDA have a financial interest in remdesivir which is why it favors that drug

Gilead has yet to indicate that it will allow others outside the FDA to view any data it or the FDA holds or encourage third party research.

Research indicates that GS-441524 is less toxic than remdesivir so can be given in higher doses and is much easier to make than remdesivir plus has many other benefits over remdesivir.

Texas University researchers have responded to questions about why GC-441524 is probably superior - see statnews article already linked from May 2020 and the following q&a posted


A private Dr highlighted GS-441524 in Feb 2020 in a Tampa Fl news article.

According to journalists and others Gilead has not responded to requests to clarify its position on allowing GS-441524 for the treatment for cats and seems unwilling to provide any meaningful response to requests for clarification on a range of matters about GS-441524 including encouraging meaningful covid-19 research. Gileads responses have focused on stressing remdesivir benefits or passing comments about any researching of GS-441524

Gilead and the FDA jointly developed the drug Remdesivir however Gilead registered the patent without including any FDA rights though later published research papers clearly list the many government scientists involved


GS-441524 was also developed and patented with other parties and is a very similar drug to remdesivir. The Gilead patent life for Remdesivir is 7+ years longer than the GS-441524 patent and for other reasons the GS-441524 patent may be less profitable for Gilead.

Gilead has prior history of trying to exclude the FDA from participating in patent royalities the FDA contributed to developing.


In a letter to leadership of Gilead Sciences, Inc., the National Institutes of Health, the Food and Drug Administration, and the Biomedical Advanced Research and Development Authority, Public Citizen and two scientists specializing in cancer drug development offer a detailed summary of scientific evidence suggesting that the experimental antiviral drug GS-441524 may be a better drug than the closely-related drug remdesivir to treat COVID-19. The letter asks Gilead and the federal agencies either to work collaboratively to promptly pursue the development of GS-441524 as a treatment for COVID-19 or to publicly explain and provide evidence as to why doing so is not scientifically or medically feasible.

The links to the open letter to Gilead and the FDA and other articles and info are below


Open letter to Gilead and FDA



FDA response

View: https://twitter.com/i/web/status/1297572580853915648


“reviewed the literature and agree that this compound merits further exploration,”

Michael Abrams Phd , health researcher at Public Citizen and lead author of the letter to the FDA states “Such further study of the drug is long overdue, especially given the evidence that GS-441524 may be cheaper and easier to manufacture and more amenable to administration in inhaled or oral forms than remdesivir.”

“We hope that Gilead will respond similarly and commit to working collaboratively with the NIH to study the potential of GS-441524, even if it means the company may reap lower profits than expected from the marketing of remdesivir,” Abrams added.



Research on GS-441524


Lab tests have suggested GS-441524 is active against SARS-CoV-2, and it is apparently similar or superior to the effects of remdesivir at levels that do not cause much toxicity, according to the Anderson researchers, who want to run their own tests. They also maintain the compound is more easily synthesized than remdesivir, so it should be easier to create oral versions and make higher doses.


The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

10 cats were infected with FIP and then treated with GS-441524. All 10 cats recovered.

Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA

Gilead Sciences, Foster City, CA, USA

Accepted 14 April 2018



Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses
Susan Amirian
Julie K.Levy

Public Health & Healthcare Program, Texas Policy Lab, School of Social Sciences, Rice University, Houston, TX, USA

Maddie's Shelter Medicine Program, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA

Accepted 24 March 2020,



The Atlantic

The background to the long term Cat research GS-441524 and the treatment people are using to cure cats of a deadly coronavirus that kills around 95% of infected cats

Around 5 years ago Gilead sent University researchers 25 or 30 molecules, drawn from the large library of drug candidates that pharmaceutical companies typically maintain.

Two of the molecules worked marvelously in cat cells infected with the FIP virus: GS-441524 and GS-5734, the latter of which is now better known as remdesivir.

After Ebola trials found little benefit, remdesivir became a drug in search of a (human) disease.

Both molecules were effective, so Pedersen decided to pursue the simpler one, GS-441524. He then infected 10 cats with FIP and dosed them with GS-441524. All 10 cats recovered.

“We almost fell out of our chairs,” says Weigner.

in a follow-up field trial of 31 pets with naturally acquired FIP, 25 ultimately made it—an unheard-of recovery rate.

Despite the success, Gilead refused to license GS-441524 for use in cats.

While Pedersen was testing GS-441524 in cats, a different virus—a human virus—was raging halfway around the world in West Africa: Ebola. The virus that causes Ebola is not a coronavirus, but remdesivir is unusually broad-acting for an antiviral, and early results against Ebola were promising. So promising, in fact, that the company was eyeing FDA approval of remdesivir in humans.

According to Pedersen, Gilead worried that the cat research could impede the approval process for remdesivir. Because GS-441524 and remdesivir are so similar, any adverse effects uncovered in cats might have to be reported and investigated to guarantee remdesivir’s safety in humans.

Gilead’s caution about generating unnecessary cat data is standard industry practice. “One of the rules in drug development is never perform a test you don’t have to, if the results could be problematic,” says Richard Sachleben, a retired pharma-industry researcher.

(Gilead declined to comment for this story.)




Pharmalot
The U.S. government contributed research to a Gilead remdesivir patent — but didn’t get credit
By Ed Silverman @Pharmalot
May 8, 2020

September 2015 in which Gilead sought a U.S. patent for a using the compound for any number of coronavirus infections. Although the code Gilead assigned to the compound – GS-5734 – does not appear in the body of the application, experts who have reviewed the chemical structure say the compound is remdesivir.

One month later, some of the same Gilead employees whose names appeared on the patent application were listed as co-authors on a Nature research paper – along with numerous government scientists – showing remdesivir, specifically, held promise in fighting Ebola and other coronaviruses. The paper also noted testing was conducted at high-risk security labs run by the federal government.

The role played by the federal government in developing remdesivir to combat coronaviruses has, in fact, involved various grants to universities, as well as contributions from government personnel at such agencies as the U.S. Army Medical Research Institute of Infectious Diseases, according to Knowledge Ecology International, an advocacy group that first disclosed these connections.

But while it remains unclear the extent to which federal funds contributed to the R&D, the patent is of particular interest because it is tangible evidence that government work yielded something of potential financial value to the company. Yet government employees are not listed as inventors, which one expert suggested should be corrected, especially in an era when federally financed research might be leveraged to collect royalties or, arguably, lower the price of medicines.

“In this case, all of these scientists were really working together very intimately on research that led to the molecule,” said Arti Rai, a Duke University law professor who specializes in intellectual property and a former U.S. Patent and Trademark Office official, who is researching remdesivir patents and the role played by the federal government.

“Gilead actually had a huge number of patents on the molecules, but had to do a tremendous amount of work to figure out which variations of the various molecules would work against the biological models the government had. This patent illustrates the essence of why collaboration between the public and private sectors is important, not just in terms of money, such as grants, but resources.”

“What really matters is how much money the government has put into research, but if their names were on there, it would help to make the case there was a lot of in-kind contribution from the government,” she explained. “Right now, if Gilead tried to assert rights (in response to a patent challenge), there would be no way to know there was some government right to a license to the patent.”

Generally, one must play connect the dots to find government assistance. For instance, the National Institutes of Health gave grants to several universities whose researchers worked with Gilead scientists. Their efforts appeared in a 2018 paper in the American Society for Microbiology, which found remdesivir can combat coronaviruses, noted Tahir Amin, who heads the Initiative for Medicines, Access, and Knowledge, an advocacy group that challenged various Gilead patents on hepatitis C medicines.

We asked Gilead, which several months ago sought to add claims to the patent, for comment and will update you accordingly.

Numerous consumer advocates, academics, and lawmakers have argued that prescription drugs invented with taxpayer dollars should be affordable to Americans. Public Citizen estimated that U.S. taxpayers contributed $70.5 million to remdesivir R&D overall.

“Since we’re paying for the research, we shouldn’t expect to be at disadvantage,” said Jamie Love of Knowledge Ecology International. “The argument that you have to have a high price because a company made big investments is harder to justify when there was a large public financing role in the R&D. A high company may say a high price is necessary, but the rationale falls apart when we’re paying for the R&D.”

Gilead has often been at the center of such debates. As noted previously, the drug maker and the federal government filed dueling lawsuits over patents that formed the basis of a best-selling HIV prevention pill called Truvada. The government claims Gilead should pay royalties on its patents, which stemmed, in part, from taxpayer funding, while the company has argued the government patents are invalid.


Feb 2020 news article on GS-441524
By Dr. Joette Giovinco

Dr. Joette Giovinco wrote a press article highlighting GS-441524 in Feb 2020 as a promising Covid-19 treatment




Remdesivir is a promising antiviral drug and works by inhibiting the activity of RNA dependent RNA polymerase (RdRp).

GS-441524 is a feline infectious peritonitis virus (FIPV) inhibitor and a predominant metabolite of Remdesivir that is superior to Remdesivir against COVID-19.

First GS-441524 shows comparable efficacy in cell-based models of primary human lung and cat cells infected with the coronavirus. GS-441524 could strongly inhibit feline infectious peritonitis virus (FIPV), with an EC50of 0.78 μM.

Recent research in coronavirus-infected nonhuman primates demonstrated problems with remdesivir that inadvertently showed the antiviral effectiveness of GS-441524. In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream..... injection of remdesivir in NHP results in GS-441524 being present in serum at concentrations 1000-fold higher than remdesivir throughout a 7-day treatment course (Figure 3b).

Last but not the least, GS-441524 is capable of treating cats suffering from feline infectious peritonitis (FIP) with a 96% cure rate. Importantly, coupled with the robust antiviral activity of GS-441524 against FIP, these data compel further investigations into the therapeutic and prophylactic utility of GS-441524 against SARS-CoV-2.

All in all, GS-441524, a FIPV inhibitor, is a predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19.







GILEAD owns patent rights to GS-441524 (2009) and Remdesivir (2017); The 2009 patent of GS-441524 may be invalid due to prior art: as we have seen in the GILEAD vs MERK trial (which Merk initially won), there is a large amount of prior art in the nucleoside space that may invalidate the GS-441524 patent.


Covid-19 treatnent research drug GC376

A final thought - great research is being done on Covid-19 some of it is below on another drug also tested on cats with FIP. However this drug GC376 was much less successful than GS-441524

The researchers of GC376 are clearly very good and professional

However how is it Covid-19 treatment research can be done on GC376 with cat coronavirus FIP treatment effectiveness being cited as one of the reasons for rapid research, and yet this not happen on GS-441524 when its almost 100% effective against the cat coronavirus FIP and worked well against other coronaviruses plus GS-441524 is potentially better than remdesivir ?

antiviral GC376 out of Kansas State University had previously been tested but only seven out of 20 cats had gone into remission. Those results seemed impressive at the time, but GS-441524 appeared to be even better

"Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1-7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission."


Research on GC376


Published: 27 August 2020

Feline coronavirus drug GC376 inhibits the main protease of SARS-CoV-2 and blocks virus replication


GC376 has been used to successfully treat FIP in cats as its breakdown product, GC373, effectively inhibits the Mpro of FCoV. Analogs of these drugs also inhibited the MERS CoV Mpro and blocked viral replication in cells at an EC50 of 0.5 μM14. Our studies show GC376 and GC373 to be effective inhibitors of SARS-CoV-2 Mpro, in agreement with previous studies showing GC373 and GC376 possess broad specificity against the Mpro of coronaviruses and calciviruses (Supplementary Table 2)10,13,14,22. Clearly, these drugs need to be advanced quickly into human trials for COVID-19. SARS-CoV-2 is the cause of COVID-19 and is a virus with a significant mutation rate23. Also, in some patients the virus has persisted longer than 2 months with some possibility of re-infection24. Vaccines are critically important, but still likely a year or more away as this virus may present vaccine challenges.

There are many clinical trials testing drugs re-purposed from their original indications. Remdesivir, a polymerase inhibitor developed as a treatment for Ebola virus25 had initially been used in compassion cases, and is now FDA approved for emergency use in patients with COVID-19......

How was a long known treatment found and blocked for a new condition?
 
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How was a long known treatment found and blocked for a new condition?
Critics say Gilead has blocked the use of or studies on its drug GS-441524 on Covid-19 because Gilead will make less money despite evidence that GS-441524 will be as or more effective than Gileads other drug remdesivir

Both remdesivir (GS-5734) and GS-441524 are owned in full or part by Gilead and are almost identical chemically.

GS-441524 is much simpler to make than remdesivir so much cheaper to produce and has extensively used on cats to cure about 96% of cats with a fatal cat coronavirus - FIP

GS-441524 is the "predominant metabolite of Remdesivir"

GS-441524 was successful in prior lab studies against coronaviruses SARS, MERS and FIP a near 100% fatal cat coronavirus that GS-441524 cures

Some years ago Gilead and the University of California did tests with GS-441524 on cats with FIP both in lab settings and later on pet cats with the 100% fatal cat coronavirus FIP - GS-441524 was an almost 100% successful cure

Gilead refused to allow GS-441524 to be manufactured to treat cats, so it has for many years been made without permission and used by cat owners and cat charities to successfully and rapidly treat cats who are in critical and fatal condition

The patent life for GS-441524 is much shorter than remdesivir and could be challanged or need to be shared and so Gilead will make less money.

Gilead has a history of seeking to exclude the FDA for sharing patents it has a right to due to the FDA facilities, researchers and indirect financial support - with the need for patent litigation between the FDA and Gilead being publically discussed over previous drugs

Gilead failed to included the FDA in its remdesivir patent filings despite published research and papers crediting FDA researchers and facilities for much of the work and development

As early as Feb 2020 Drs were pointing out GS-441524 could be a very effective covid-19 treatment


Further research shows GS-441524 is the effective compound in remdesivir

High Potency Remdesivir studies show GS-441524 is the effective compound that is left in lungs to treat covid-19

Robert O. Williams III, study co-author said “And importantly, new data from the study regarding the formulation of remdesivir with leucine suggest that the TFF formulation can significantly prolong the duration of the remdesivir nucleoside analog GS-441524 in the lung, providing a important therapeutic benefit for lung delivery.”

 
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In May 2020 Cancer researchers from the University of Texas set out in some detail why Gileads drug GS-441524 was superior to Gileads Remdesivir as a Coronavirus treatment. This was based both on animals trials and previous research on GS-441524. In some animals trials GS-441524 was compared directly with Remdesivir, as an anti coronavirus treatment, with GS-441524 becoming the preferred treatment.

Gilead developed Remdesivir with the FDA, however it is much more complicated and expensive to make than GS-441524 and could be less effective but for numerous reasons Gilead will make more money from Remdesivir and the FDA may also has a financial interest in remdesivir.

Critics say a long known promising Covid-19 treatment GS-441524 has not been studied and that it was delibrately blocked, for profit reasons, from Covid-19 researchers, having proper access to all the information on it.

Prior lab studies have shown that GS-441524 is effective against coronaviruses SARS, MERS and FIP a near 100% fatal cat coronavirus that GS-441524 had a near 100% cure rate for.

Gileads' responses have not addressed the points raised nor whether Gilead is promoting remdesivir because of its longer patent or why Gilead blocked and/or also had not encouraged or helped anyone researching the medical effectiveness of GS-441524 to resolve matters.

Gilead has for a some years also refused to explain why it has not allowed the manufacture or licensing of GS-441524 for use in cats after successful animal trials cured cats of a fatal coronavirus disease


A journalist writing in The Atlantic said "After Ebola trials in previous years found little benefit, remdesivir became a drug in search of a (human) disease."

Some years ago GS-441524 and Remdesivir were both tested against FIP a 95% fatal cat coronavirus.

Gilead was involved in these University of California animal tests providing the 25+ different drugs initially screened for use in the trials and credited in the published research.

The trials showed both remdesivir and GS-441524 were effective against FIP however GS-441524 was preferred and cured 100% of the coronavirus infected cats in the university tests. Later field tests on pet cats confirmed GS-441524s effectiveness

Strangely Gilead has refused to allow anyone to make or legally use GS-441524 on cats (or any animals or humans) despite repeated requests related to cats

Thus long before Covid-19 cat owners were forced to buy GS-441524 on the black market to treat their cats and Gilead did nothing nor provided any explaination

Critics say Gilead blocks GS-441524 as it is easier and cheaper to make and so will compete against Remdesivir meaning Gilead will make less money

Following Gileads and the FDAs focus on remdesivir and their failure to enter into meaningful discussions or research on GS-441524, an open letter was written to the FDA and Gilead by a citizens advocacy group asking

why GS-441524 was not being studied as a Covid-19 treatment and

that the FDA and others be encouraged to do research or

to explain why it was not scientifically and medically possible to do so.

The citizens group writing the letter has formally raised medical and other matters over many years, is non political and has been critical of both the Trump administration and the FDA and their response to covid-19 and other citizens rights matters. For example they separately launched legal action against the FDA over what is said to be an unsafe medical device that the FDA failed to withdraw.

The FDA has just responded to the GS-441524 coronavirus research letter saying that they have now

“reviewed the literature and agree that this compound merits further exploration,”

View: https://twitter.com/i/web/status/1297572580853915648


The questions the seem important are

why has it taken so long to start this work,

why did it take a citizens group not doctors or researchers or health officials to get this to happen and

will others also now be encouraged to also do research or will it remain a limited work within the FDA

will Gilead do all it can to help serious researchers resolve if GS-441524 is more effective than remdesivir

does the FDA have a financial interest in remdesivir which is why it favors that drug

Gilead has yet to indicate that it will allow others outside the FDA to view any data it or the FDA holds or encourage third party research.

Research indicates that GS-441524 is less toxic than remdesivir so can be given in higher doses and is much easier to make than remdesivir plus has many other benefits over remdesivir.

Texas University researchers have responded to questions about why GC-441524 is probably superior - see statnews article already linked from May 2020 and the following q&a posted


A private Dr highlighted GS-441524 in Feb 2020 in a Tampa Fl news article.

According to journalists and others Gilead has not responded to requests to clarify its position on allowing GS-441524 for the treatment for cats and seems unwilling to provide any meaningful response to requests for clarification on a range of matters about GS-441524 including encouraging meaningful covid-19 research. Gileads responses have focused on stressing remdesivir benefits or passing comments about any researching of GS-441524

Gilead and the FDA jointly developed the drug Remdesivir however Gilead registered the patent without including any FDA rights though later published research papers clearly list the many government scientists involved


GS-441524 was also developed and patented with other parties and is a very similar drug to remdesivir. The Gilead patent life for Remdesivir is 7+ years longer than the GS-441524 patent and for other reasons the GS-441524 patent may be less profitable for Gilead.

Gilead has prior history of trying to exclude the FDA from participating in patent royalities the FDA contributed to developing.


In a letter to leadership of Gilead Sciences, Inc., the National Institutes of Health, the Food and Drug Administration, and the Biomedical Advanced Research and Development Authority, Public Citizen and two scientists specializing in cancer drug development offer a detailed summary of scientific evidence suggesting that the experimental antiviral drug GS-441524 may be a better drug than the closely-related drug remdesivir to treat COVID-19. The letter asks Gilead and the federal agencies either to work collaboratively to promptly pursue the development of GS-441524 as a treatment for COVID-19 or to publicly explain and provide evidence as to why doing so is not scientifically or medically feasible.

The links to the open letter to Gilead and the FDA and other articles and info are below


Open letter to Gilead and FDA



FDA response

View: https://twitter.com/i/web/status/1297572580853915648


“reviewed the literature and agree that this compound merits further exploration,”

Michael Abrams Phd , health researcher at Public Citizen and lead author of the letter to the FDA states “Such further study of the drug is long overdue, especially given the evidence that GS-441524 may be cheaper and easier to manufacture and more amenable to administration in inhaled or oral forms than remdesivir.”

“We hope that Gilead will respond similarly and commit to working collaboratively with the NIH to study the potential of GS-441524, even if it means the company may reap lower profits than expected from the marketing of remdesivir,” Abrams added.



Research on GS-441524


Lab tests have suggested GS-441524 is active against SARS-CoV-2, and it is apparently similar or superior to the effects of remdesivir at levels that do not cause much toxicity, according to the Anderson researchers, who want to run their own tests. They also maintain the compound is more easily synthesized than remdesivir, so it should be easier to create oral versions and make higher doses.


The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

10 cats were infected with FIP and then treated with GS-441524. All 10 cats recovered.

Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA

Gilead Sciences, Foster City, CA, USA

Accepted 14 April 2018



Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses
Susan Amirian
Julie K.Levy

Public Health & Healthcare Program, Texas Policy Lab, School of Social Sciences, Rice University, Houston, TX, USA

Maddie's Shelter Medicine Program, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA

Accepted 24 March 2020,



The Atlantic

The background to the long term Cat research GS-441524 and the treatment people are using to cure cats of a deadly coronavirus that kills around 95% of infected cats

Around 5 years ago Gilead sent University researchers 25 or 30 molecules, drawn from the large library of drug candidates that pharmaceutical companies typically maintain.

Two of the molecules worked marvelously in cat cells infected with the FIP virus: GS-441524 and GS-5734, the latter of which is now better known as remdesivir.

After Ebola trials found little benefit, remdesivir became a drug in search of a (human) disease.

Both molecules were effective, so Pedersen decided to pursue the simpler one, GS-441524. He then infected 10 cats with FIP and dosed them with GS-441524. All 10 cats recovered.

“We almost fell out of our chairs,” says Weigner.

in a follow-up field trial of 31 pets with naturally acquired FIP, 25 ultimately made it—an unheard-of recovery rate.

Despite the success, Gilead refused to license GS-441524 for use in cats.

While Pedersen was testing GS-441524 in cats, a different virus—a human virus—was raging halfway around the world in West Africa: Ebola. The virus that causes Ebola is not a coronavirus, but remdesivir is unusually broad-acting for an antiviral, and early results against Ebola were promising. So promising, in fact, that the company was eyeing FDA approval of remdesivir in humans.

According to Pedersen, Gilead worried that the cat research could impede the approval process for remdesivir. Because GS-441524 and remdesivir are so similar, any adverse effects uncovered in cats might have to be reported and investigated to guarantee remdesivir’s safety in humans.

Gilead’s caution about generating unnecessary cat data is standard industry practice. “One of the rules in drug development is never perform a test you don’t have to, if the results could be problematic,” says Richard Sachleben, a retired pharma-industry researcher.

(Gilead declined to comment for this story.)




Pharmalot
The U.S. government contributed research to a Gilead remdesivir patent — but didn’t get credit
By Ed Silverman @Pharmalot
May 8, 2020

September 2015 in which Gilead sought a U.S. patent for a using the compound for any number of coronavirus infections. Although the code Gilead assigned to the compound – GS-5734 – does not appear in the body of the application, experts who have reviewed the chemical structure say the compound is remdesivir.

One month later, some of the same Gilead employees whose names appeared on the patent application were listed as co-authors on a Nature research paper – along with numerous government scientists – showing remdesivir, specifically, held promise in fighting Ebola and other coronaviruses. The paper also noted testing was conducted at high-risk security labs run by the federal government.

The role played by the federal government in developing remdesivir to combat coronaviruses has, in fact, involved various grants to universities, as well as contributions from government personnel at such agencies as the U.S. Army Medical Research Institute of Infectious Diseases, according to Knowledge Ecology International, an advocacy group that first disclosed these connections.

But while it remains unclear the extent to which federal funds contributed to the R&D, the patent is of particular interest because it is tangible evidence that government work yielded something of potential financial value to the company. Yet government employees are not listed as inventors, which one expert suggested should be corrected, especially in an era when federally financed research might be leveraged to collect royalties or, arguably, lower the price of medicines.

“In this case, all of these scientists were really working together very intimately on research that led to the molecule,” said Arti Rai, a Duke University law professor who specializes in intellectual property and a former U.S. Patent and Trademark Office official, who is researching remdesivir patents and the role played by the federal government.

“Gilead actually had a huge number of patents on the molecules, but had to do a tremendous amount of work to figure out which variations of the various molecules would work against the biological models the government had. This patent illustrates the essence of why collaboration between the public and private sectors is important, not just in terms of money, such as grants, but resources.”

“What really matters is how much money the government has put into research, but if their names were on there, it would help to make the case there was a lot of in-kind contribution from the government,” she explained. “Right now, if Gilead tried to assert rights (in response to a patent challenge), there would be no way to know there was some government right to a license to the patent.”

Generally, one must play connect the dots to find government assistance. For instance, the National Institutes of Health gave grants to several universities whose researchers worked with Gilead scientists. Their efforts appeared in a 2018 paper in the American Society for Microbiology, which found remdesivir can combat coronaviruses, noted Tahir Amin, who heads the Initiative for Medicines, Access, and Knowledge, an advocacy group that challenged various Gilead patents on hepatitis C medicines.

We asked Gilead, which several months ago sought to add claims to the patent, for comment and will update you accordingly.

Numerous consumer advocates, academics, and lawmakers have argued that prescription drugs invented with taxpayer dollars should be affordable to Americans. Public Citizen estimated that U.S. taxpayers contributed $70.5 million to remdesivir R&D overall.

“Since we’re paying for the research, we shouldn’t expect to be at disadvantage,” said Jamie Love of Knowledge Ecology International. “The argument that you have to have a high price because a company made big investments is harder to justify when there was a large public financing role in the R&D. A high company may say a high price is necessary, but the rationale falls apart when we’re paying for the R&D.”

Gilead has often been at the center of such debates. As noted previously, the drug maker and the federal government filed dueling lawsuits over patents that formed the basis of a best-selling HIV prevention pill called Truvada. The government claims Gilead should pay royalties on its patents, which stemmed, in part, from taxpayer funding, while the company has argued the government patents are invalid.


Feb 2020 news article on GS-441524
By Dr. Joette Giovinco

Dr. Joette Giovinco wrote a press article highlighting GS-441524 in Feb 2020 as a promising Covid-19 treatment




Remdesivir is a promising antiviral drug and works by inhibiting the activity of RNA dependent RNA polymerase (RdRp).

GS-441524 is a feline infectious peritonitis virus (FIPV) inhibitor and a predominant metabolite of Remdesivir that is superior to Remdesivir against COVID-19.

First GS-441524 shows comparable efficacy in cell-based models of primary human lung and cat cells infected with the coronavirus. GS-441524 could strongly inhibit feline infectious peritonitis virus (FIPV), with an EC50of 0.78 μM.

Recent research in coronavirus-infected nonhuman primates demonstrated problems with remdesivir that inadvertently showed the antiviral effectiveness of GS-441524. In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream..... injection of remdesivir in NHP results in GS-441524 being present in serum at concentrations 1000-fold higher than remdesivir throughout a 7-day treatment course (Figure 3b).

Last but not the least, GS-441524 is capable of treating cats suffering from feline infectious peritonitis (FIP) with a 96% cure rate. Importantly, coupled with the robust antiviral activity of GS-441524 against FIP, these data compel further investigations into the therapeutic and prophylactic utility of GS-441524 against SARS-CoV-2.

All in all, GS-441524, a FIPV inhibitor, is a predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19.







GILEAD owns patent rights to GS-441524 (2009) and Remdesivir (2017); The 2009 patent of GS-441524 may be invalid due to prior art: as we have seen in the GILEAD vs MERK trial (which Merk initially won), there is a large amount of prior art in the nucleoside space that may invalidate the GS-441524 patent.


Covid-19 treatnent research drug GC376

A final thought - great research is being done on Covid-19 some of it is below on another drug also tested on cats with FIP. However this drug GC376 was much less successful than GS-441524

The researchers of GC376 are clearly very good and professional

However how is it Covid-19 treatment research can be done on GC376 with cat coronavirus FIP treatment effectiveness being cited as one of the reasons for rapid research, and yet this not happen on GS-441524 when its almost 100% effective against the cat coronavirus FIP and worked well against other coronaviruses plus GS-441524 is potentially better than remdesivir ?

antiviral GC376 out of Kansas State University had previously been tested but only seven out of 20 cats had gone into remission. Those results seemed impressive at the time, but GS-441524 appeared to be even better

"Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1-7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission."


Research on GC376


Published: 27 August 2020

Feline coronavirus drug GC376 inhibits the main protease of SARS-CoV-2 and blocks virus replication


GC376 has been used to successfully treat FIP in cats as its breakdown product, GC373, effectively inhibits the Mpro of FCoV. Analogs of these drugs also inhibited the MERS CoV Mpro and blocked viral replication in cells at an EC50 of 0.5 μM14. Our studies show GC376 and GC373 to be effective inhibitors of SARS-CoV-2 Mpro, in agreement with previous studies showing GC373 and GC376 possess broad specificity against the Mpro of coronaviruses and calciviruses (Supplementary Table 2)10,13,14,22. Clearly, these drugs need to be advanced quickly into human trials for COVID-19. SARS-CoV-2 is the cause of COVID-19 and is a virus with a significant mutation rate23. Also, in some patients the virus has persisted longer than 2 months with some possibility of re-infection24. Vaccines are critically important, but still likely a year or more away as this virus may present vaccine challenges.

There are many clinical trials testing drugs re-purposed from their original indications. Remdesivir, a polymerase inhibitor developed as a treatment for Ebola virus25 had initially been used in compassion cases, and is now FDA approved for emergency use in patients with COVID-19......

High Potency Remdesivir and normal remdesivir are effectively just producing another cheaper Gilead drug GS-441524

Studies have shown GS-441524 is the effective compound that remdesivir (GS-5734) is converted into and GS-441524 is left in lungs to treat Covid-19 infection. So why not use GS-441524 rather than remdesivir.

Robert O. Williams III, study co-author said “And importantly, new data from the study regarding the formulation of remdesivir with leucine suggest that the TFF formulation can significantly prolong the duration of the remdesivir nucleoside analog GS-441524 in the lung, providing a important therapeutic benefit for lung delivery.”


There has been no real news about what research the FDA has started doing on GS-441524 despite the FDA belatedly admitting in August they had now

“reviewed the literature and agree that this compound (GS-441524) merits further exploration,”

Gilead has refused to research GS-441524 which has a shorter patent than remdedivir, despite it being almost identical to remdesivir and the main metabolite of remdesivir.


The treatment study about high potency remdesivir is different to the work on GS-441524 but supports the questions raised

It looks like different researchers at the University of Texas are working on remdesivir and GS-441524. It is unclear if this will cause a conflict of interest or not or if any co-ordination is taking place

Further research indicates a highly effective fatal cat coronavirus treatment drug GS-441524 (also owned by Gilead) is a direct competitor, more effective and a cheaper treatment against Covid-19 than Gilead's remdesivir (GS-5734) treatment

For full links to published studies, news and the FDA response agreeing Covid-19 treatment research should be done on GS-441524 see link at start of this response or the start of this thread.

The FDA responded in August to an open letter to Gilead and the FDA from a well respected citizens rights group and University of Texas researchers asking why GS-441524 was not being researched as a Covid-19 treatment despite extensive long established research studies and animal treatment showing its high effectiveness against various coronaviruses and being simpler and almost identictical to remdesivir

This includes widespread use of GS-441524 over some years with a near 100% success rate as a treatment for a common and fatal cat coronavirus, and successful previous use against other coronaviruses such as SARS and MERS

Gilead failed to respond to the letter or the Texas researchers or materially address their position on GS-441524

Neither the FDA or Gilead have explained why no research on GS-441524 was carried out or even considered to date or promoted despite researchers and others setting out their findings or serious questions / comments since around Feb 2020 and certainly by May 2020

With the FDA now confirming that the long standing research on GS-441524 going back many years had merit and would now be looked into questions should be asked about the FDAs duties and why Gilead has acted against the public interest in blocking research on GS-441524 over many years and did Gilead have the right to do so ? Also has Gilead claimed rights over a patent for GS-441524 that it had only questionable rights to ?
 
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In May 2020 Cancer researchers from the University of Texas set out in some detail why Gileads drug GS-441524 was superior to Gileads Remdesivir as a Coronavirus treatment. This was based both on animals trials and previous research on GS-441524. In some animals trials GS-441524 was compared directly with Remdesivir, as an anti coronavirus treatment, with GS-441524 becoming the preferred treatment.

Gilead developed Remdesivir with the FDA, however it is much more complicated and expensive to make than GS-441524 and could be less effective but for numerous reasons Gilead will make more money from Remdesivir and the FDA may also has a financial interest in remdesivir.

Critics say a long known promising Covid-19 treatment GS-441524 has not been studied and that it was delibrately blocked, for profit reasons, from Covid-19 researchers, having proper access to all the information on it.

Prior lab studies have shown that GS-441524 is effective against coronaviruses SARS, MERS and FIP a near 100% fatal cat coronavirus that GS-441524 had a near 100% cure rate for.

Gileads' responses have not addressed the points raised nor whether Gilead is promoting remdesivir because of its longer patent or why Gilead blocked and/or also had not encouraged or helped anyone researching the medical effectiveness of GS-441524 to resolve matters.

Gilead has for a some years also refused to explain why it has not allowed the manufacture or licensing of GS-441524 for use in cats after successful animal trials cured cats of a fatal coronavirus disease


A journalist writing in The Atlantic said "After Ebola trials in previous years found little benefit, remdesivir became a drug in search of a (human) disease."

Some years ago GS-441524 and Remdesivir were both tested against FIP a 95% fatal cat coronavirus.

Gilead was involved in these University of California animal tests providing the 25+ different drugs initially screened for use in the trials and credited in the published research.

The trials showed both remdesivir and GS-441524 were effective against FIP however GS-441524 was preferred and cured 100% of the coronavirus infected cats in the university tests. Later field tests on pet cats confirmed GS-441524s effectiveness

Strangely Gilead has refused to allow anyone to make or legally use GS-441524 on cats (or any animals or humans) despite repeated requests related to cats

Thus long before Covid-19 cat owners were forced to buy GS-441524 on the black market to treat their cats and Gilead did nothing nor provided any explaination

Critics say Gilead blocks GS-441524 as it is easier and cheaper to make and so will compete against Remdesivir meaning Gilead will make less money

Following Gileads and the FDAs focus on remdesivir and their failure to enter into meaningful discussions or research on GS-441524, an open letter was written to the FDA and Gilead by a citizens advocacy group asking

why GS-441524 was not being studied as a Covid-19 treatment and

that the FDA and others be encouraged to do research or

to explain why it was not scientifically and medically possible to do so.

The citizens group writing the letter has formally raised medical and other matters over many years, is non political and has been critical of both the Trump administration and the FDA and their response to covid-19 and other citizens rights matters. For example they separately launched legal action against the FDA over what is said to be an unsafe medical device that the FDA failed to withdraw.

The FDA has just responded to the GS-441524 coronavirus research letter saying that they have now

“reviewed the literature and agree that this compound merits further exploration,”

View: https://twitter.com/i/web/status/1297572580853915648


The questions the seem important are

why has it taken so long to start this work,

why did it take a citizens group not doctors or researchers or health officials to get this to happen and

will others also now be encouraged to also do research or will it remain a limited work within the FDA

will Gilead do all it can to help serious researchers resolve if GS-441524 is more effective than remdesivir

does the FDA have a financial interest in remdesivir which is why it favors that drug

Gilead has yet to indicate that it will allow others outside the FDA to view any data it or the FDA holds or encourage third party research.

Research indicates that GS-441524 is less toxic than remdesivir so can be given in higher doses and is much easier to make than remdesivir plus has many other benefits over remdesivir.

Texas University researchers have responded to questions about why GC-441524 is probably superior - see statnews article already linked from May 2020 and the following q&a posted


A private Dr highlighted GS-441524 in Feb 2020 in a Tampa Fl news article.

According to journalists and others Gilead has not responded to requests to clarify its position on allowing GS-441524 for the treatment for cats and seems unwilling to provide any meaningful response to requests for clarification on a range of matters about GS-441524 including encouraging meaningful covid-19 research. Gileads responses have focused on stressing remdesivir benefits or passing comments about any researching of GS-441524

Gilead and the FDA jointly developed the drug Remdesivir however Gilead registered the patent without including any FDA rights though later published research papers clearly list the many government scientists involved


GS-441524 was also developed and patented with other parties and is a very similar drug to remdesivir. The Gilead patent life for Remdesivir is 7+ years longer than the GS-441524 patent and for other reasons the GS-441524 patent may be less profitable for Gilead.

Gilead has prior history of trying to exclude the FDA from participating in patent royalities the FDA contributed to developing.


In a letter to leadership of Gilead Sciences, Inc., the National Institutes of Health, the Food and Drug Administration, and the Biomedical Advanced Research and Development Authority, Public Citizen and two scientists specializing in cancer drug development offer a detailed summary of scientific evidence suggesting that the experimental antiviral drug GS-441524 may be a better drug than the closely-related drug remdesivir to treat COVID-19. The letter asks Gilead and the federal agencies either to work collaboratively to promptly pursue the development of GS-441524 as a treatment for COVID-19 or to publicly explain and provide evidence as to why doing so is not scientifically or medically feasible.

The links to the open letter to Gilead and the FDA and other articles and info are below


Open letter to Gilead and FDA



FDA response

View: https://twitter.com/i/web/status/1297572580853915648


“reviewed the literature and agree that this compound merits further exploration,”

Michael Abrams Phd , health researcher at Public Citizen and lead author of the letter to the FDA states “Such further study of the drug is long overdue, especially given the evidence that GS-441524 may be cheaper and easier to manufacture and more amenable to administration in inhaled or oral forms than remdesivir.”

“We hope that Gilead will respond similarly and commit to working collaboratively with the NIH to study the potential of GS-441524, even if it means the company may reap lower profits than expected from the marketing of remdesivir,” Abrams added.



Research on GS-441524


Lab tests have suggested GS-441524 is active against SARS-CoV-2, and it is apparently similar or superior to the effects of remdesivir at levels that do not cause much toxicity, according to the Anderson researchers, who want to run their own tests. They also maintain the compound is more easily synthesized than remdesivir, so it should be easier to create oral versions and make higher doses.


The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

10 cats were infected with FIP and then treated with GS-441524. All 10 cats recovered.

Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA

Gilead Sciences, Foster City, CA, USA

Accepted 14 April 2018



Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses
Susan Amirian
Julie K.Levy

Public Health & Healthcare Program, Texas Policy Lab, School of Social Sciences, Rice University, Houston, TX, USA

Maddie's Shelter Medicine Program, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA

Accepted 24 March 2020,



The Atlantic

The background to the long term Cat research GS-441524 and the treatment people are using to cure cats of a deadly coronavirus that kills around 95% of infected cats

Around 5 years ago Gilead sent University researchers 25 or 30 molecules, drawn from the large library of drug candidates that pharmaceutical companies typically maintain.

Two of the molecules worked marvelously in cat cells infected with the FIP virus: GS-441524 and GS-5734, the latter of which is now better known as remdesivir.

After Ebola trials found little benefit, remdesivir became a drug in search of a (human) disease.

Both molecules were effective, so Pedersen decided to pursue the simpler one, GS-441524. He then infected 10 cats with FIP and dosed them with GS-441524. All 10 cats recovered.

“We almost fell out of our chairs,” says Weigner.

in a follow-up field trial of 31 pets with naturally acquired FIP, 25 ultimately made it—an unheard-of recovery rate.

Despite the success, Gilead refused to license GS-441524 for use in cats.

While Pedersen was testing GS-441524 in cats, a different virus—a human virus—was raging halfway around the world in West Africa: Ebola. The virus that causes Ebola is not a coronavirus, but remdesivir is unusually broad-acting for an antiviral, and early results against Ebola were promising. So promising, in fact, that the company was eyeing FDA approval of remdesivir in humans.

According to Pedersen, Gilead worried that the cat research could impede the approval process for remdesivir. Because GS-441524 and remdesivir are so similar, any adverse effects uncovered in cats might have to be reported and investigated to guarantee remdesivir’s safety in humans.

Gilead’s caution about generating unnecessary cat data is standard industry practice. “One of the rules in drug development is never perform a test you don’t have to, if the results could be problematic,” says Richard Sachleben, a retired pharma-industry researcher.

(Gilead declined to comment for this story.)




Pharmalot
The U.S. government contributed research to a Gilead remdesivir patent — but didn’t get credit
By Ed Silverman @Pharmalot
May 8, 2020

September 2015 in which Gilead sought a U.S. patent for a using the compound for any number of coronavirus infections. Although the code Gilead assigned to the compound – GS-5734 – does not appear in the body of the application, experts who have reviewed the chemical structure say the compound is remdesivir.

One month later, some of the same Gilead employees whose names appeared on the patent application were listed as co-authors on a Nature research paper – along with numerous government scientists – showing remdesivir, specifically, held promise in fighting Ebola and other coronaviruses. The paper also noted testing was conducted at high-risk security labs run by the federal government.

The role played by the federal government in developing remdesivir to combat coronaviruses has, in fact, involved various grants to universities, as well as contributions from government personnel at such agencies as the U.S. Army Medical Research Institute of Infectious Diseases, according to Knowledge Ecology International, an advocacy group that first disclosed these connections.

But while it remains unclear the extent to which federal funds contributed to the R&D, the patent is of particular interest because it is tangible evidence that government work yielded something of potential financial value to the company. Yet government employees are not listed as inventors, which one expert suggested should be corrected, especially in an era when federally financed research might be leveraged to collect royalties or, arguably, lower the price of medicines.

“In this case, all of these scientists were really working together very intimately on research that led to the molecule,” said Arti Rai, a Duke University law professor who specializes in intellectual property and a former U.S. Patent and Trademark Office official, who is researching remdesivir patents and the role played by the federal government.

“Gilead actually had a huge number of patents on the molecules, but had to do a tremendous amount of work to figure out which variations of the various molecules would work against the biological models the government had. This patent illustrates the essence of why collaboration between the public and private sectors is important, not just in terms of money, such as grants, but resources.”

“What really matters is how much money the government has put into research, but if their names were on there, it would help to make the case there was a lot of in-kind contribution from the government,” she explained. “Right now, if Gilead tried to assert rights (in response to a patent challenge), there would be no way to know there was some government right to a license to the patent.”

Generally, one must play connect the dots to find government assistance. For instance, the National Institutes of Health gave grants to several universities whose researchers worked with Gilead scientists. Their efforts appeared in a 2018 paper in the American Society for Microbiology, which found remdesivir can combat coronaviruses, noted Tahir Amin, who heads the Initiative for Medicines, Access, and Knowledge, an advocacy group that challenged various Gilead patents on hepatitis C medicines.

We asked Gilead, which several months ago sought to add claims to the patent, for comment and will update you accordingly.

Numerous consumer advocates, academics, and lawmakers have argued that prescription drugs invented with taxpayer dollars should be affordable to Americans. Public Citizen estimated that U.S. taxpayers contributed $70.5 million to remdesivir R&D overall.

“Since we’re paying for the research, we shouldn’t expect to be at disadvantage,” said Jamie Love of Knowledge Ecology International. “The argument that you have to have a high price because a company made big investments is harder to justify when there was a large public financing role in the R&D. A high company may say a high price is necessary, but the rationale falls apart when we’re paying for the R&D.”

Gilead has often been at the center of such debates. As noted previously, the drug maker and the federal government filed dueling lawsuits over patents that formed the basis of a best-selling HIV prevention pill called Truvada. The government claims Gilead should pay royalties on its patents, which stemmed, in part, from taxpayer funding, while the company has argued the government patents are invalid.


Feb 2020 news article on GS-441524
By Dr. Joette Giovinco

Dr. Joette Giovinco wrote a press article highlighting GS-441524 in Feb 2020 as a promising Covid-19 treatment




Remdesivir is a promising antiviral drug and works by inhibiting the activity of RNA dependent RNA polymerase (RdRp).

GS-441524 is a feline infectious peritonitis virus (FIPV) inhibitor and a predominant metabolite of Remdesivir that is superior to Remdesivir against COVID-19.

First GS-441524 shows comparable efficacy in cell-based models of primary human lung and cat cells infected with the coronavirus. GS-441524 could strongly inhibit feline infectious peritonitis virus (FIPV), with an EC50of 0.78 μM.

Recent research in coronavirus-infected nonhuman primates demonstrated problems with remdesivir that inadvertently showed the antiviral effectiveness of GS-441524. In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream..... injection of remdesivir in NHP results in GS-441524 being present in serum at concentrations 1000-fold higher than remdesivir throughout a 7-day treatment course (Figure 3b).

Last but not the least, GS-441524 is capable of treating cats suffering from feline infectious peritonitis (FIP) with a 96% cure rate. Importantly, coupled with the robust antiviral activity of GS-441524 against FIP, these data compel further investigations into the therapeutic and prophylactic utility of GS-441524 against SARS-CoV-2.

All in all, GS-441524, a FIPV inhibitor, is a predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19.







GILEAD owns patent rights to GS-441524 (2009) and Remdesivir (2017); The 2009 patent of GS-441524 may be invalid due to prior art: as we have seen in the GILEAD vs MERK trial (which Merk initially won), there is a large amount of prior art in the nucleoside space that may invalidate the GS-441524 patent.


Covid-19 treatnent research drug GC376

A final thought - great research is being done on Covid-19 some of it is below on another drug also tested on cats with FIP. However this drug GC376 was much less successful than GS-441524

The researchers of GC376 are clearly very good and professional

However how is it Covid-19 treatment research can be done on GC376 with cat coronavirus FIP treatment effectiveness being cited as one of the reasons for rapid research, and yet this not happen on GS-441524 when its almost 100% effective against the cat coronavirus FIP and worked well against other coronaviruses plus GS-441524 is potentially better than remdesivir ?

antiviral GC376 out of Kansas State University had previously been tested but only seven out of 20 cats had gone into remission. Those results seemed impressive at the time, but GS-441524 appeared to be even better

"Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1-7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission."


Research on GC376


Published: 27 August 2020

Feline coronavirus drug GC376 inhibits the main protease of SARS-CoV-2 and blocks virus replication


GC376 has been used to successfully treat FIP in cats as its breakdown product, GC373, effectively inhibits the Mpro of FCoV. Analogs of these drugs also inhibited the MERS CoV Mpro and blocked viral replication in cells at an EC50 of 0.5 μM14. Our studies show GC376 and GC373 to be effective inhibitors of SARS-CoV-2 Mpro, in agreement with previous studies showing GC373 and GC376 possess broad specificity against the Mpro of coronaviruses and calciviruses (Supplementary Table 2)10,13,14,22. Clearly, these drugs need to be advanced quickly into human trials for COVID-19. SARS-CoV-2 is the cause of COVID-19 and is a virus with a significant mutation rate23. Also, in some patients the virus has persisted longer than 2 months with some possibility of re-infection24. Vaccines are critically important, but still likely a year or more away as this virus may present vaccine challenges.

There are many clinical trials testing drugs re-purposed from their original indications. Remdesivir, a polymerase inhibitor developed as a treatment for Ebola virus25 had initially been used in compassion cases, and is now FDA approved for emergency use in patients with COVID-19......

Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment

Victoria C. Yan* and Florian L. Muller

University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States

Cite this: ACS Med. Chem. Lett. 2020, 11, 7, 1361–1366
Publication Date:June 23, 2020
Copyright © 2020 American Chemical Society

 
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In Feb 2020 Professor Pedersen from the University of California was interviewed about Covid-19 pointing out that he had discovered and conducted clinical trials on a very successful cure for a fatal cat coronavirus and that this work was being ignored by public health officials and others.

This drug is Gilead's GS-441524 which Gilead has refused over many years to allow any licensing, research, production or official use in animals let alone humans.

Dr. Niels Pedersen has spent 50 years studying the coronavirus, specifically a strain found in cats, called Feline Infectious Peritonitis or FIP, for short.

View: https://youtu.be/YMhDyTcOv3o


Some other Drs and researchers also highlighted GS-441524 as a potentially important Covid-19 cure but were ignored.

However GS-441524 has been unofficially used over many years to treat cats with the 100% fatal coronavirus FIP and has about a 96% successful cure rate

GS-441524 is almost identical to Gilead's preferred Covid-19 drug Remdesivir (GS-5734)

GS-441524 was also effective against the coronaviruses SARS and MERS

Further researchers have set out based on historic and current research testing and animal use that GS-441524 is probably safer less toxic and more effective against Covid-19 than Remdesivir plus also cheaper and simpler to make and can probably be taken orally unlike Remdesivir

It should be noted that Remdesivir actually converts into GS-441524 in the human body to be effective against Covid-19 and GS-441524 becomes the main metabolite of Remdesivir - so a big question is why give Remdesivir and not GS-441524?

At the very least GS-441524 should have been extensively researched as a Covid-19 treatment.

Requests to Gilead for info on GS-441524 or assistance with research were extensively stonewalled until a recent open letter to the FDA and Gilead made public what was going on.

The FDA subsquently admitted in writing that GS-441524 should be researched as a Covid-19 treatment



Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment

Victoria C. Yan* and Florian L. Muller

Cite this: ACS Med. Chem. Lett. 2020, 11, 7, 1361–1366
Publication Date:June 23, 2020



Further info is in my previous posts
 
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The following info comes mostly from a web site that focuses on cats with FIP the fatal cat coronavirus. Links below

University of California was actively involved in developing GS-441524 as a treatment for the fatal cat coronavirus FIP and later researchers pointed out it could be equally effective against Covid-19 which Gilead did not investigate.

It looks like Gilead may have decided to move forward with using GS-441524 as a treatment for the fatal Cat coronavirus FIP at the same time that Remdesivir was removed from the list of approved ebola treatments - around August 2019

However once Covid-19 emerged in Jan 2020 Gilead turned its attention back to Remdesivir and dropped GS-441524

For economic reasons ?

Gilead would prefer its Remdesivir patent to be used as a Covid-19 treatment and not GS-441524 which is jointly owned and may also be subject to other patent challanges. See previous posts

At some earlier point it seems that Gilead had filed the patent for GS-441524 in only its name but then in August 2019 amended the application to add the University of California.

I cannot find much separate supporting info however it seems that the patent for GS-441524 is now jointly owned by Gilead and the University of California plus this filing was made at about the same time in August 2019 that Remdesivir was removed from the list of NIH approved ebola drugs.

This might explain Gileads reluctance to promote or research GS-441524 as a treatment for humans or animals until it thought Remdesivir had little future.

It could also explain Gileads back tracking on GS-441524 for cats or humans once Covid-19 came along to save Remdesivir in Jan 2020

Gileads actions on Remdesivir Vs GS-441524 as a Covid-19 or FIP treatment have certainly not been transparent or helpful.

I could be shooting at clouds but as I found this info I thought it was better in the public domain to let others dig deeper to seeif anything is "there there"

See links and info below

Gilead mulls repositioning failed Ebola drug in China virus - Jan 2020


The patent rights to GS-441524 are Gilead Sciences, Inc, and the Regents of the University of California (a patent applicant change was made on the 08/12/2019 to add the Regents of the University of California)



The following is a footnote at the bottom of the related page link

On August 12, 2019 Anthony Fauci, Director of the NIH’s National Institute of Allergy and Infectious Diseases announced that Remdesivir had been removed from the current Ebola clinical trials, citing a mortality rate of 53%.




Gilead has filed the Remdesivir patent in its sole name but the FDA probably has a good claim to jointly own the patent.

Remdesivir, an experimental COVID-19 treatment, has benefited significantly from public funding. Based off publicly available data, Public Citizen estimates that taxpayers are contributing at least $70.5 million to develop remdesivir.[1] The real number is likely higher. We trace the story below.

 
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A recent public posting on 17th September 2020 by a legal firm (Kershaw, Cook & Talley) on its web site about ongoing litigation confirms that Gilead has a history of withholding more effective less harmful drugs it owns, developed at the same time, for commercial reasons - and only releasing the better drug 15 years later as a "new" improved treatment once the more toxic and damaging drug was nearing the end of its patent life

Kershaw, Cook & Talley - statements and comments

Gilead Sciences, Inc. and the federal government have been accused of withholding [GS-441524] a promising treatment for COVID-19, also known as the coronavirus, that may offer “significant advantages” over Remdesivir, currently Gilead’s sole drug undergoing clinical trials for COVID-19 treatment, according to Public Citizen, a non-profit consumer advocacy organization. Kershaw, Cook & Talley is actively pursuing a lawsuit alleging that Gilead engaged in nearly identical conduct regarding the marketing of TDF- and TAF-based drugs used in the treatment and prevention of HIV infection over 20 years earlier.

The allegations Public Citizen brought forward concerning Gilead’s conduct with respect to Remdesivir and GS-441524 is remarkably similar to its alleged conduct in a lawsuit pending in San Francisco Superior Court on behalf of thousands of individuals represented by Kershaw, Cook & Talley and other law firms across the United States. In this lawsuit, plaintiffs allege that Gilead developed TDF-based drugs — commonly known as Viread®, Truvada®, Truvada for PrEP®, Atripla®, Complera® and Stribild® — for the treatment and prevention of HIV infection, while it simultaneously developed TAF-based drugs proved to be safer and at least equally effective at much smaller doses. Gilead’s own studies demonstrated that TDF had a much higher risk of severe side effects, including bone loss and kidney failure. Gilead chose to sell TDF and kept TAF (the safer drug) off the market for nearly 15 years. Plaintiffs allege that this strategy was enacted solely to maximize Gilead’s profits and extend its patent protection for these life-saving drugs. Once the patent on TDF ran out, Gilead then came out with TAF and marketed it as a “new and improved” drug with fewer side effects than TDF.

To date, almost 18,000 plaintiffs have filed lawsuits against Gilead, which have been consolidated in San Francisco Superior Court for pretrial discovery.

In an August 4 letter, Public Citizen and scientists at MD Anderson Cancer Center alleged that both Gilead and the U.S. Department of Health and Human Services (HHS) have been sitting on a drug known as GS-441524 despite the fact that it has shown superior antiviral behavior against the coronavirus in cell cultures compared to Remdesivir. Gilead is accused of keeping GS-441524 on the shelf in order to extend its monopoly over drugs that can be used to treat COVID-19.

“It is sadly predictable that Big Pharma responds to a global pandemic by trying to bring to market only those drugs that maximize its profits,” said Michael Abrams, health researcher with Public Citizen’s Health Research Group and lead author of the letter. “What is alarming here is that federal scientists and Trump administration regulators appear to be willing partners with Gilead in decisions that run distinctly counter to the government’s primary imperative of advancing public health during this worldwide crisis.”

Kershaw, Cook & Talley



Gilead is in a patent dispute with the FDA over patents the FDA was almost certainly entitled to and directly or indirectly funded and/or researched - this patent dispute is related to the same drug Truvada that Gilead is accused of bringing to market even though it had also developed a less toxic and more and/or as effective alternative which Gilead released only many years later



Financial Times report that the company didn’t seek patent protection for the drug to cover PrEP use in the U.S. As a result, the drugmaker could owe $1 billion or more in royalties and damages to the government, according to the newspaper. Gilead disagreed with that conclusion and argued its Truvada patents cover all uses for the drug, the FT reported.

 
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I agree with you - too much wad

I did send a message to a journalist late this week

That was after I found the recent litigation background statement about Gilead, with the specific references to Gilead and GS-441524, plus the 2019 confirmation from Gilead it was blocking research on GS-441524 to support Remdesivir.

I guess I write too much for people to read and its not always very clear

If you know any journalists send them the links to these posts

I have learned about whats happened slowly over time. This has been a way to record the info publically. The info is hidden all over the place

Something does not add up - why block research into a hugely successful coronavirus drug during this crisis in favor of a similar drug that has only limited benefit.


Lets summarize for anyone who hasnt read the extensive previous posts/wad

I only post things if there are credible web links to the info - I have backed it up on the public online wayback archieve incase it should disappear from the web

GS-441524 and Remdesivir are almost chemically identical and produce the same anti coronavirus metabolite

A range of independent university researchers set out GS-441524 looks much more effective against covid-19 than Remdesivir - they show how it is much less toxic, delivers much more of the same anti coronavirus metabolite than Remdesivir ever could, is much cheaper to make and much easier to give to patient etc etc.

GS-441524 was 100% effective in clinical lab animal trials against a 100% fatal cat coroavirus. 96% effective when given to pet animals with the infection.

Gileads GS-441524 patent is less profitable than its Remdesivir patent - as its jointly owned and has a shorter life.

There is nothing stopping Gilead testing both drugs side by side - they produce the same active anti coronavirus metabolite

Gilead is facing litigation claims from 18,000 people that it held back a less toxic better drug until the patent expired on a worse drug that damaged and may have killed people. Gilead had the research for both drugs all the time but it is claimed wanted to make money on both drugs so held back the better drug to release 15 years later as a new improved version. Gilead already faces patent breach claims from the FDA for both the two litigation related drugs and will also over remdesivir if the FDA acts as it should. Gilead has settled some other serious charges

Gilead officially said in 2019 long before coronavirus that it would not allow research development or sales of GS-441524 for humans or animals until Remdesivir was approved by the FDA

This despite having 100% clinical evidence GS-441524 was a cure for a 100% fatal coronavirus illness but no similar clinical evidence to support remdesivir

Note Remdesivir had pretty much failed to treat anything and in 2019 it is set out that it was removed from medical use by the FDA.

After coronavirus Gilead continued to stonewall third party research requests and did not do any GS-441524 research itself etc

There are enough serious people now admitting something is wrong in not researching GS-441524 - even the FDA cannot hide any more after an open letter was sent in August and the FDA agreed to urgently do research in late August. Gilead has not been clear about the priority it will give such research

Did some good guys in the FDA know all along that research should be done on GS-441524 ?

Things do not add up but the mainstream press is ignoring it, and even the specialist press only writes on a limited specific points

No one is asking why did the FDA and Gilead not research GS-441524 and what communication was there before the open letter to the FDA and Gilead forced them to say it should have been and now will be researched ?

Others fast tracked university Covid-19 lab research into a drug similar to GS-441524 that being GC376 - both tested at UC Davis

[GC376 was only about 1/3 as effective as GS-441524 ]

University Professors now report the GC376 drug has been positioned for fast human clinical trials in Canada and FDA approval in the USA all because its patent owners allowed 2020 lab research to go forward and previous clinical trial research shows GC376 acted against a fatal cat coronavirus virus - GC376 was never FDA approved for animal use

UC Davis studies of both drugs show GS-441524 was light years better and was pretty much a 100% coronavirus cure in live animals compared to about 35% for GC376

I have nothing against GC376, the research looks great and well done. However it makes not researching GS-441524 even less understandable

All this is public info

Given whats going on with covid-19 and the status Remdesivir was given by the FDA some answers are due on GS-441524.

I guess the mainstream press are staying away from asking these questions and upsetting big pharma in favor of getting some of the $30 billion pharma spent in 2019 on marketing and advertizing.

Big pharma/healthcare are also the far biggest spenders on lobbying and donating to politicians.

I hoped people here might be interested and look into this themselves - as the process of finding treatments will effect all of us

I found a livescience staff writer article about Remdesivir and GS-441524 and posted on that page as well - which Valentine commented on


Hope other people can take this forward.
 
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