Comparison of Major COVID-19 Early Treatment Pharmaceuticals    Late Treatment Pharmaceutical
       
Considerations Paxlovid Molnupiravir Curcumin Vitamin D Zinc HCQ Ivermectin Considerations Bamlanivimab + Casirivimab + Sotrovimab Considerations Remdesivir Notes  
 
FDA Endorsed (EUA) as a COVID-19 Early Treatment Therapy EUA (12-22-21) EUA (12-23-21) No No No No No FDA Endorsed (EUA) as a COVID-19 Early Treatment Therapy EUA (2-9-21) [See Notes Below] EUA (11-21-20) EUA (5-26-21)* FDA Endorsed (EUA) as a COVID-19 Late Treatment Therapy EUA (5-1-20)* Hydroxychloroquine (HCQ) and Ivermectin (IVM) are FDA approved for other human uses. Doctors quite often prescribe off-label use.**  
Is the Drug Currently Patented Yes Yes No No No No No Is the Drug Currently Patented Yes Yes Yes Is the Drug Currently Patented Yes Paxlovid is a combination of Ritonavir + Nirmatrelvir.  
Sponsor for FDA COVID-19 EUA  Pfizer Merck No One No One No One No One No One Sponsor for FDA COVID-19 EUA  Eli Lilly Regeneron Pharmaceuticals GlaxoSmithKline Sponsor for FDA COVID-19 EUA  Gilead Sciences There appears to be no Consumer Advocate in the FDA EUA process.  
Primary Data Source FDA.gov C19early.com/PL FDA.gov C19MP.com C19Curcumin.com VDmeta.com C19Zinc.com HCQmeta.com IVMmeta.com Primary Data Source FDA.gov (2020) FDA.gov (2021) C19ly.com/meta.html FDA.gov C19regn.com/meta.html FDA.gov C19sv.com Primary Data Source FDA.gov C19rmd.com The Non-FDA webpages are professionally maintained by independent experts.  
   
 
Total Number of all COVID-19 Studies 1 13 1 13 19 85 32 350 89 Total Number of all COVID-19 Studies 1 1 14 1 21 1 7 Total Number of all COVID-19 Studies 5 38 Most of the patented drug studies were done by the manufacturers.***  
   Total Number of all Study Participants 2,085 41,303 1,408 15,517 4,006 140,678 35,459 459,719 133,038    Total Number of all Study Participants 452 1,035 24,423 799 47,101 583 9,907    Total Number of all Study Participants 32,333 124,717 The more subjects tested, the better: 1000+ would be desirable.  
Number of Early Treatment Studies (ET) 1 10 1 9 8 8 4 36 36 Number of Early Treatment Studies (ET) 1 1 8 1 15 1 6 Number of Late Treatment Studies (LT) 5 36 ET = all COVID-19 Early Treatment studies. More studies indicate more scientists involved, and different perspectives. More participants means more statistical soundness.  
   Number of ET Study Participants 2,085 34,082 1,408 4,714 771 43,422 3,010 56,721 56,911    Number of ET Study Participants 452 1,035 17,980 799 31,102 583 9,547    Number of LT Study Participants 32,333 123,983
   Overall ET Effectiveness 88% 45% 30% 43% 46% 67% 61% 62% 63%    Overall ET Effectiveness 74% 70% 69% 67% 57% 85% 37%    Overall LT Effectiveness ~10% 15% It VERY important to understand that this is the Relative benefit, not Absolute.****  
Number of ET Hospital/Death Studies (ET1) 1 7 1 6 3 5 4 22 19 Number of ET Hospital/Death Studies (ET1) 1 1 8 1 8 1 5 Number of LT Death Studies (LT1) 5 35 ET1 = a subset of ET, including only ET studies whose primary focus was on Hospitalization or Mortality (e.g., not viral load reduction, etc.).  
   Number of ET1 Study Participants 2,085 33,951 1,408 9,969 374 42,974 3,010 54,132 55,380    Number of ET1 Study Participants 452 1,035 17,980 799 29,368 583 8,619    Number of LT1 Study Participants 32,333 123,506  
Number of Larger ET1 Studies (ET2) 1 1 1 3 ~ 1 (3) 2 1 1+ 1+ Number of Larger ET1 Studies (ET2) 1 1 2 1 1 1 2 Number of Larger LT1 Studies (LT2) 1 2 ET2 = a subset of ET1. One large ET1 study was used. (Three smaller Curcumin ET1 studies were combined as they are considered equivalent to one study.)  
   Number of ET2 Study Participants 2,085 30,322 1,408 8,436 374 42,846 1,957 10,479 28,048    Number of ET2 Study Participants 452 1,035 15,022 799 9,682 583 7,290    Number of LT2 Study Participants 30,451 70,197  
   ET2 Hospital & Death Reduction 88% 45% 30% 30% 89% 48% 53% 83% 59%    ET2 Hospital & Death Reduction 74% 70% 67% 67% 77% 85% 50%    LT2 Death Reduction 5% 4% Same comment as above.****   See the Primary Data Sources for info.  
     
 
Number of Human Doses 100,000+ 100,000+ Many Billions Many Billions Many Billions Billions 4± Billion Number of Human Doses 10± thousand 90± thousand 100± thousand 100± thousand Number of Human Doses 1± million Estimates. The more the better, as this provides real-world safety and effectiveness data.  
Any Long Term Safety Data No* No* Yes Yes Yes Yes Yes Any Long Term Safety Data No No No Any Long Term Safety Data No Where Yes, the data are based on billions of human doses.  
Safe for Persons with Common Diseases Unknown* Unknown* Yes Yes Yes Yes Yes Safe for Persons with Common Diseases Unknown Unknown Unknown Safe for Persons with Common Diseases Unknown Examples of Common Diseases are: Cancer, Diabetes, Parkinson's, etc.  
Potential Side Effects Serious* Serious* Trivial Trivial Trivial Moderate Mild Potential Side Effects Serious Moderate to Serious Moderate to Serious Moderate to Serious Potential Side Effects Serious An approximation based on what appears on FDA documents and on <Drugs.com>.  
Details about Potential Side Effects FDA's Warnings FDA's Warnings Side Effects Side Effects Side effects Side Effects Side Effects Details about Potential Side Effects Withdrawn FDA's Warnings FDA's Warnings FDA's Warnings Details about Potential Side Effects Original FDA Warnings** Links to FDA documents and <Drugs.com> webpages.  
Restrictions 12+ Years Old 18+ Years Old No No No No No Restrictions Only for High Risk and Non-vaccinated 12+ Years; High Risk; Non-vaccinated 12+ Years; High Risk; Non-vaccinated Restrictions Yes: See FDA Warnings An approximation based on what appears on FDA documents and on <Drugs.com>.  
How is it administered Pill Pill Pill Pill Pill Pill Pill How is it administered Injection or infusion Injection or Infusion Infusion How is it administered Infusion A patient-taken pill is preferable to an injection/infusion that may require a hospital setting.  
   
 
Total Treatment Drug Cost $500± $700± $5± $5± $5± $50± $50± Total Treatment Drug Cost $2,500± $2100± $2100± Total Treatment Drug Cost $3100± Approximate cost for five (5) days of COVID-19 treatment, excluding cost of doctor visit.  
How Drug is Purchased Prescription Prescription OTC OTC OTC Prescription Prescription How Drug is Purchased Prescription Prescription Prescription How Drug is Purchased Prescription Prescription is negative as valuable time is lost in that process.  
 Color Code:  Green = Positive Black = Neutral Red = Negative For Color Code ranges, see here   *Revised EUA: 3-25-22 * Revised EUAs: 8-28-20; 10-1-20; 10-16-20
What is an Emergency Use Authorization (EUA)? Understanding the Regulatory Terminology of Potential Preventions and Treatments for COVID-19 Despite the claimed high effectiveness of sotrovimab (see above), the FDA took the relatively unusual step of issuing a revised EUA for it. The new EUA states that it is not effective for the latest COVID-19 variant. **Updated FDA Warnings
* Some Additional Safety Data —  There are multiple FDA EUA documents and modifications of the remdesivir (veklury) case. For example, on the NIH website they list five studies that they say were the basis for the FDA granting an EUA. On another FDA document (<tinyurl.com/y2dj5fj6>) they say the number of studies is three. On another, they say one! To give them the maximum benfit, we listed five (see above).
Some Molnupiravir Safety Concerns Note: Paxlovid includes Ritonavir and Nirmatrelvir —> Ritonavir Side Effects Unable to find side-effects, etc. listed for Nirmatrelvir. —> Three disconcerting new study results about Paxlovid: here here & here.
Note 1: One of the serious side effects that the FDA EUA pharmaceuticals may have (that the non-EUA options have less of, or none), is a potential conflict with pregnancy.
Note 2: This fascinating study revealed that eighteen common medical conditions were not tested prior to the COVID-19 vaccine EUAs.  A similar situation exists with all of the FDA EUA pharmaceuticals above.
** Physicians prescribe "off-label" pharmaceuticals quite frequently. Two good discussions are  here (NIH) and here (FDA).
*** Major pharmaceutical companies have the funds (and experience) to run large, well-controlled studies on drugs where they would like to get FDA EUAs. Non-patented drugs have no such financial backer.
        All studies have a chance of confirmation bias, especially when there is a significant economic incentive at stake.
**** A good, layperson explanation of Relative vs Absolute improvement is here.
A brief write-up about some of the takeaways from this data is here. A more abbreviated version of this data is  here.
Using Monoclonal Antibodies (MAs) against COVID-19. Study: Vaccines and Most Monoclonal Antibodies are Not Effective against Omicron Study: Benefits And Risks Of Administering Monoclonal Antibody Therapy For COVID-19. FDA gives remdesivir full Approval 10-22-20.
         Bamlanivimab was granted an FDA EUA: 11/9/20. It was then withdrawn (4-16-21) due to adverse results. Initial Bam authorization Bam Revocation   FDA Updates remdesivir Approval 1-21-22.
              The FDA subsequently granted Bamlanivimab a second EUA, only if it was used with Etesevimab. The info in the 2nd & 3rd columns in the Bam section is for that combination.  
         "Casirivimab +" means that it is combined with Imdevimab. The combination is called REGEN-COV.   See our detailed report on remdesivir:
         For all three MAs, the FDA does not have a link to the clinical trial cited as their justification for the EUAs. (They do for the Pfizer and Merck pills...)   here.
         The FDA documents for each of the three Monoclonal Antibodies (MA) has a statement similar to: There are limited clinical data available for MA. Serious and unexpected adverse events may occur that have not been previously reported with MA use.
SOME CONCLUSIONS —
    It's startling that the FDA would give an EUA to a drug with only a 10%± relative benefit!  See this commentary.
    Likewise incomprehensible is that the FDA would give an EUA to a drug with only a 30% relative benefit (3% absolute)!  See this commentary. (Merck News Release)
            This is particularly puzzling considering that the FDA has publicly stated that they would not give an EUA to a COVID-19 vaccine unless it had an effectiveness of over 50%. See FDA Statement.
    The referenced studies appear to indicate that the chances of Early Treatment success against COVID-19 are likely superior to Paxlovid by combining HCQ with all of the three OTCs listed here.  
    The referenced studies also appear to indicate that the chances of Early Treatment success against COVID-19 with IVM, or HCQ, or all of the three OTCs listed here, are superior to Molnupiravir.
    The referenced studies appear to indicate that the chances of Early Treatment success against COVID-19 are likely better than  any of the MAs by combining HCQ with all of the three OTCs listed here.  
    Compared to the patented drugs, the non-patented alternatives: have lower likelihood of adverse health complications, plus the pharmaceutical cost is considerably less.
    Based on the above information — especially the Molnupiravir data — there is no reason why the FDA should not have given HCQ and IVM their EUA blessing.
    It's also quite revealing that the FDA gave an EUA to three MAs only after single, small (<800 people) clinical trials. Why isn’t this standard applied to the non-patented options?
    It is a major disservice to the public that the FDA does not have a Consumer Advocate to sponsor non-patented pharmaceuticals for FDA EUAs and approvals.
         Likewise, the FDA should have adequate funding to run clinical trials on pharmaceuticals recommended by their Consumer Advocate.
Always consult with a qualified physician before taking any medications, OTC (Over-The-Counter) or otherwise.
For questions, comments or possible errors (please provide the evidence), email physicist John Droz, jr.
Revision: 8-7-22