Off-Roading with the FDA

It appears the FDA is now willing to deviate from its “bedrock mission” of guiding the public with accurate science-based information to a different road emphasizing variable political interests.

“The deep state, or whoever, over at the FDA is making it very difficult  .  .  .   @SteveFDA“, addressing you directly with your Twitter handle (trump). 

FDA is endorsing twitter as a mechanism to broadcast actions with and by Commissioner Dr. Hahn. Tweeting:

I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.” SteveFDA.

It would appear the FDA is now under direction of trump who is taking it down roads not traveled by the FDA in the past with the medical profession in the back seat. Some are not so willing to go along for the ride.

“We cannot entrust the health of 330 million Americans to a person who is subservient to President Trump’s whims, unprecedented promotion of unproven therapies, outrageous lies, and political motivations.” Dr. Eric J. Topol, MD, the editor-in-chief of Medscape

Medscape has three interesting articles critiquing the FDA. The first article reviews the  expansion of remdesivir usage, the second covers FDA Commissioner Dr. Stephen Hahn actions, and the last is questioning the FDA’s Covid decisions.   The first two articles were published on August 31st and the last on September 2nd. Typically, I read the articles and then go on to the comments section to see what medical practitioners have to say. I would suggest you too read the articles and then read the comments which can reveal a different perspective.  The comments can be useful and insightful.

First article; “FDA Expands Remdesivir Use for All COVID-19 Hospitalized Patients” regardless of when it was contracted. It is my understanding remdesivir is a drug which has its greatest impact early on before the Covid virus replicates.

The second article I am linking too is(?) a letter written by Dr. Eric J. Topol, MD, the editor-in-chief of Medscape to the current FDA Commissioner: “Dear Commissioner Hahn: Tell the Truth or Resign.” Dr. Eric Topol has written an open letter to Dr. Stephen Hahn who replaced Dr. Scott Gottlieb as Commissioner of the FDA. In it he accuses Dr. Hahn of misusing “emergency use authorizations” (EUAs) to promote 3 drugs having little scientific evidence in support of their efficacy. Here again, I would ask you to read the article and then go to the comments (>450). There is good information there which you may not get ordinarily by surfing the web. The comments are informative about the drugs being promoted without completing the clinical trial requiem and subsequent decisions being made which may be in error due to a lack of testing.

The last Medscape article asks; “What Do You Think of the FDA’s COVID-19 Decisions?” The article has a questionnaire to be answered by medical personnel, which I skipped and went to the posted results. It has some interesting data information reviews the “three emergency use authorizations (EUAs)” DR, Topol states are not evidence-based:

– One EUA for hydroxychloroquine on March 30 (revoked in June for lack of evidence),

– one for convalescent plasma on August 23, and

– an expanded EUA for remdesivir to treat “any” hospitalized COVID-19 patient, not just those with severe disease.

My opinion, which others may dispute what I have to say:

Every article I have read on HCQ, the failures in countries in question or US entities (such as the VA) have used different dosages (higher) than what was used in Korea, France, Costa Rica and a few other places. As I read, the failed treatment were started later, after Covid was discovered, and beyond the initial ten days in which success was achieved. The testing facilities did not duplicate what was done in prior successful patterns of treatment. Why would any entity not try to duplicate the “supposed” treatment plan which was touted to be successful? If the process is duplicated, the hypothesis is tested.  You can form your own conclusion to that question. Henry Ford Health System in a multi-hospital assessment, tested HCQ utilizing ~2500 patients participating. “Treatment with hydroxychloroquine, azithromycin, and in combination in patients hospitalized with COVID-19.”  The data is there have at it.

The second article is discussing a process and procedure utilizing convalescent plasma which is barely off the ground in the treatment of Covid.  HHS Secretary Alex Azar; a “35% improvement in survival is a pretty substantial clinical benefit. If the data continues to pan out, of 100 people who are sick with COVID-19, 35 would have been saved because of the admission of plasma.”

Dr. Eric Topol; “The statement was based on a preprint, which by definition has not been peer-reviewed and published by Mayo Clinic’s Michael Joyner and coauthors. It is a retrospective, observational study of over 35,000 patients who received convalescent plasma, without any controls or untreated patients for comparison. The claim of reduction of mortality is totally unsubstantiated.  If the preprint data held up in a proper randomized controlled trial, it would be avoiding deaths of 3 or 4 people per 100 who would have died. ”

We are reminded by Dr. Topol of the FDA’a goal:

“FDA is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health.”

Finally, we come to Gilead’s remdesivir. “Gilead Sciences announced that it would begin charging a US price of $3,120 for a 5-day course of remdesivir as a treatment for COVID-19.” The pricing has been modeled by the ICER, which everyone says is expensive for a 5-day treatment course of action. Not to justify the price of it, maybe I am missing some additional information for their reasoning?

“Remdesivir is an expensive drug, costing approximately $3000 per treatment,” Dr. Topol

There is something in error as the cost is far less than what is being said here. Perhaps I am misreading?  Cost recovery for remdesivir has been mostly achieved. I am assuming Dr. Topol means the pricing for remdesivir has been established by the ICER which Gilead stated as a  “5-day treatment course.” The “initial ICER-COVID model suggested a price of approximately $4,500 per treatment course, whether that course is 10 or 5 days.”

Remdesivir is effective when used early on after contracting Covid (I am not going to discuss why). It has shown limited ability in later stages of treatment the same as HCQ in combination with other drugs. There is a history to Gilead’s remdesivir being approved as an orphan drug initially and then being switched back. It is all in the demand and the returns. Covid is no longer a rare disease as expected and more profit can be made from remdesivir under normal pricing due to demand. Declared orphan drugs have a lower demand and are given special consideration due to the rarity of the disease and low demand (<200,000). A drug can still be an Orphan drug if declared such before it exceeds 200,000 also. Timely declaration is important.

Simplistically stated, how does remdesivir (GS-5734) work?  Nucleoside/tide analogues (remdesivir) mimics the structure of a natural nucleoside or nucleotide such that they are recognized by viruses and attach to them. Due to those structural modifications they stop or interrupt viral replication which prevents the virus from multiplying and infecting more cells in the body. They are known as direct-acting antivirals. This is the case for remdesivir, which works by blocking the coronavirus’s RNA polymerase – one of the key enzymes this virus needs in order to replicate its genetic material (RNA) and proliferate in an infected person. It is a pro-drug.  Remdesivir is metabolized and undergoes a sequence of five bioactivation steps before it becomes triphosphate, the active compound that impedes replication of the virus. You are probably wondering why I am going to such a lengthy explanation. Be patient, I am getting there.

Gilead has another antiviral nucleoside analogue (I picked up a whole new vocabulary since the onslaught of Covid). GS-441524, a pro-drug the body converts into a GS-441524 triphosphate in just three steps.”GS-441524 is either similar too or more potent than remdesivir against SARS-CoV-2 in cell culture causing some researchers arguing that GS-441524 would be better than remdesivir for the treatment of COVID.”

It was originally  thought remdesivir would activate quicker than GS-441524 in human cells infected with the SARS and MERS coronaviruses. Data from primary human airway epithelial cells showed no statistically significant difference in potency between the two compounds. The data aligns with previous reports on the similar effectiveness of remdesivir and GS-441524 in coronavirus-infected cat cells. GS-441524 was used to treat cats with feline infectious peritonitis, a progressive and usually fatal disease caused by a coronavirus. It displayed remarkable safety and therapeutic efficacy, with 96% of cats recovering after treatment. Gilead should perhaps focus on remdesivir’s ancestor rather than remdesivir. It has been claimed it will convert to a triphosphate faster.

Back to MedScape articles. Read them and then go to the comments section to see what the medical practitioners are saying. You will find most of the doctors will not administer a drug unless it has been FDA approved. Secondly, hospitals are against administering convalescent plasma. Thirdly, the letter from Dr. Topol to trump-appointed FDA Commissioner Dr. Hahn is condemning as Hahn is approving drugs without clinical trials which in one case the drug labeled HCQ was reversed. To be redundant, I usually read the article and then go on to read the comments by the medical people. The comments can be useful, insightful, and interesting.