version 2, 2020-09-20
- In the recommended doses (200 mg on day 1, 100 mg per day after that), Remdesivir (RDV) has only insignificant antiviral effect against SARS-COV-2.
- RDV treatment in accordance with the current recommendations is likely to significantly increase mortality in severe COVID-19 patients.
- Only 3 (three) useful clinical trials have been cited by the FDA in the two EUAs they issued for RDV and by the NIH COVID-19 Treatment Panel in its recommendations to use RDV for COVID-19.
- Only one of the referenced studies claimed clinical benefits of RDV for COVID-19 patients, but it is invalidated by conflicts of interest, misleading reporting of results, suspicious data, and multiple significant changes in the protocol in the middle of the study
- The lack of RDV’s antiviral effect for SARS-COV-2 is consistent with the results of its trials for respiratory coronavirus on animals.
- The lack of RDV’s antiviral effect for SARS-COV-2 is also consistent with hindsight interpretation of early in vitro trials. RDV and Chloroquine (CQ) have shown similar selective antiviral effects in vitro. However, in vivo, CQ accumulates in lung tissue, while RDV does not. Even with this accumulation, CQ/HCQ is only effective in a synergetic combination with additional medicines, such as Azithromycin (AZ) and/or Zinc.
This paper analyzes all clinical trials referenced by the FDA and the NIH COVID-19 Treatment Panel, in their decisions to issue Emergency Use Authorizations and recommendations for the use of Remdesivir (RDV) for COVID-19 treatment.
Surprisingly, only three comparative clinical trials were cited in four documents issued by the FDA and the NIH, and only one of these studies asserted that RDV treatment was beneficial for COVID-19 patients.
Only one of the three studies – Wang Y. et al. – was conducted without gross conflicts of interest in favor of Gilead Sciences, Inc., the rights owner and manufacturer of RDV. This study found that RDV had no effect in the treatment of COVID-19.
The remaining two studies (Beigel et al., May 22, and Spinner et al., August 21) were marred by gross methodological defects, including changing the primary endpoints in the middle of the study, invalidating their results. Beigel et al. was supposed to be double blind, but it was not. Spinner et al. was not placebo controlled.
Beigel et al. is the only one of these studies that asserted that RDV had clinical benefits in COVID-19 patients. In addition to other defects, it incorrectly reported mortality. The article’s text selectively reported the mortality rates after 14 days from the start of treatment, which was lower in the RDV group. However, the results for RDV group deteriorated immediately after that. The mortality rates in severe patients, and only slightly decreased mortality in moderate patients, and severe patients had much higher mortality after RDV treatment than after placebo. The in-depth analysis of this trial’s conduct and reporting results indicates a strong bias in favor of the researched product. With a correction for that bias, RDV is likely to increase mortality in the general population of COVID-19 patients, and to sharply increase mortality in severe patients.
Each of the FDA and NIH decisions on RDV only cited one or two useful clinical trials, as follows:
FDA EUA for RDV, May 1: cited Beigel et al. unpublished data
NIH Panel on RDV, May 12: cited Beigel et al., Wang Y. et al.
NIH Panel on RDV, July 24: cited Beigel et al.
FDA EUA for RDV, August 28: cited Beigel et al., Spinner et al.
The two additional studies cited in the FDA and NIH documents were: Goldman et al. (compared a 5-day RDV treatment course against a 10-day RDV treatment course, with no control group) and Grein et al., (a summary of selected cases from Gilead’s early compassionate treatment with RDV, with no control group). Neither of these studies are randomized controlled trials (RTC), nor are they observational studies. They did not compare results of RDV treatment to anything else and could not provide any information in favor of the drug’s effectiveness or safety.
The in-vitro and animal studies also show that RDV is not an effective antiviral against SARS-COV-2.
The author declares no conflict of interest.
No funding was provided for this work.
All relevant ethical guidelines have been followed.