Eric Topol to Stephen Hahn/FDA: “Tell the Truth or Resign”

An open letter from Eric Topol to Dr.Stephen Hahn details a number of glaring mistakes at the FDA which threaten its credibility and its mission.

Here’s the link: Dear Commissioner Hahn: Tell the Truth or Resign

The letter points to three high profile, politically-fraught decisions at the FDA:

  1. Authorization of hydroxychloroquine
    • “Immediately after President Trump widely and aggressively promoted hydroxychloroquine as a “miracle drug,” on March 30, 2020, you granted an Emergency Use Authorization (EUA) for this drug without any sufficient or meaningful supportive evidence”
  2. Authorization of convalescent plasma
    • “This is a major advance…[A]nd a 35% improvement in survival is a pretty substantial clinical benefit. What that means is — and if the data continue to pan out — [of] 100 people who are sick with COVID-19, 35 would have been saved because of the admission of plasma.” Every part of that statement is incorrect and a blatant misrepresentation of the data.
  3. Authorizaton of remdesevir
    • The third breach of evidence-based data was your EUA issued August 28, 2020 broadening the remdesivir approval to include any patient hospitalized with moderate COVID-19. There are insufficient data to support this approval, as it is based on small, open-label studies with subjective endpoints.

Dr. Topol worries that Dr. Hahn will further erode confidence in the FDA by approval of a SARS-CoV-2 vaccine prematurely.  “Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA.”

Not Curing Obesity with Fecal Microbiota Transplantation & More on Remdesivir

A recent pilot (n=22) double-blind study (JR Allegrett et al. Clin Gastroenterol Hepatol 2020; 18: 855-63) pours cold water on the idea that repopulating one’s microbiome would be helpful in treating obesity.

In this study, the authors examined obese patients without diabetes, nonalcoholic steatohepatitis, or metabolic syndrome.  In the treatment group, patients received FMT by capsules: 30 capsules at week 4 and then a maintenance dose of 12 capsules at week 8.  All FMT was derived from a single lean donor.

Key findings:

  • There were no significant changes in mean BMI at week 12 in either group.
  • Patients in the FMT group had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001).  In addition, bile acid profiles became more similar to the donor.

My take: Though this was a small study, it suggests that changing the microbiome by itself is likely insufficient to result in significant weight loss.

Related blog posts:

JH Beigel et al. NEJM DOI: 10.1056/NEJMoa2007764 (May 22, 2020): Full text: Remdesivir for the Treatment of Covid-19 — Preliminary Report

This was a a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement (n=1063).

Key findings:

  • Faster recovery for remdesivir recipients: 11 days vs 15 days
  • Lower mortality rate: 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70, 95% CI, 0.47 to 1.04) (mortality difference did not reach statistical significance)

 

 

NEJM: Compassionate Use of Remdesivir

Full report, NEJM, J Grein et al. April 10, 2020, DOI: 10.1056/NEJMoa2007016: Compassionate Use of Remdesivir for Patients with Severe Covid-19

53 of 61 had adequate data for inclusion.  Indications of severe COVID-19: at baseline, 57% required mechanical ventilation and 4 (8%) were receiving ECMO.

With a median follow-up of 18 days, Key findings:

  • 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated.
  • 25 patients (47%) were discharged
  • 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.
  • By 28 days of follow-up, the cumulative incidence of clinical improvement, as defined by either a decrease of 2 points or more on the six-point ordinal scale or live discharge, was 84%

My take: Given the severity of the disease, this therapy looks promising. However, the authors note that “measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy.”

For each oxygen-support category, percentages were calculated with the number of patients at baseline as the denominator. Improvement (blue cells), no change (beige) and worsening (gray) in oxygen-support status are shown. Invasive ventilation includes invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO), or both. Noninvasive ventilation includes nasal high-flow oxygen therapy, noninvasive positive pressure ventilation (NIPPV), or both.