IDWeek 2022: COVID-19 News for Clinical Practice or FDA Consideration

Paul G. Auwaerter, MD


November 09, 2022

This transcript has been edited for clarity.

Hello. I'm Paul Auwaerter with Medscape Infectious Diseases. Many of us were happy to be back meeting in person at IDWeek in Washington in mid-October, which was the first time in 3 years.

There were many excellent presentations, but I thought I would focus on a few of the late-breaker COVID-19 presentations that would be interesting for you to know about in terms of either incorporating into your practice or perhaps some interesting presentations that will be in front of the US Food and Drug Administration (FDA) soon.

The first drug I'd like to mention is sabizabulin. This is a colchicine-like molecule that's a microtubular disruptor, but it works a bit differently by targeting two different sites on microtubules, and it's thought to have both antiviral and anti-inflammatory properties.

This drug was reported in an interim way this past July in NEJM Evidence, when 204 patients who had severe COVID-19 were randomized to standard of care or this drug, which was given up to 21 days. The study found a rather significant 24.9% absolute reduction or 55% relative reduction in mortality that was followed up to 60 days.

What was somewhat unusual in this multicenter trial, which included patients from the United States and Brazil, was a high mortality rate of 45% in the placebo group. This was done earlier in the pandemic, but in the Delta and early Omicron phases.

Added in a late-breaker session was a subset analysis of this group that looked at patients only on low-flow or supplemental oxygen, but who also had risk factors for hospitalization. This only numbered 88 patients (so much smaller) who fell into that World Health Organization (WHO) ordinal scale of four. The analysis found that the mortality rate there dropped from 27.6% among placebo to 5.2%. Again, this was a significant reduction, although the high mortality among placebo recipients, even in this mild to moderate group of COVID-19, is a bit surprising.

Also, this drug did correlate with reduced hospital length of stay, falling from 24 to 13 days. Intensive care unit (ICU) care for those that required it was reduced 17 to 4 days and ventilator days decreased from 17 to 3 days. In this current Omicron era, whether the drug's effect on mortality would be as large is probably not the case; there is a much lower mortality rate because people are more immunized or have had infection and are granted immunity. This is a well-tolerated drug and will be presented in November in front of the FDA.

There are two other trials I thought I would report on briefly for you. The ACTIV-6 trial was a multi-arm trial that looked at repurposed drugs, including ivermectin, fluticasone inhaler, and fluvoxamine, which was compared with placebo during the Delta and early Omicron waves.

The primary endpoint was resolution of symptoms for 3 days. This study was unique because it looked at these repurposed drugs, but it was conducted via telemedicine visits with direct mailing to the participant. There might be somewhat of a lag in terms of starting the medications as opposed to people running out that day to the store.

Regardless, this was a generally younger group than in some of the other studies, even in outpatient COVID-19, and there were few hospitalizations. Ultimately, there were no differences in outcomes in terms of resolution of symptoms for 3 days. The drugs were generally without significant adverse effects, although there was one death in the ivermectin arm.

I also noticed that the ivermectin data arm was published in JAMA this past week, and that reference is included below.[1] This is yet another nail in the coffin, I think, for repurposed drugs, and I thought the way this trial was conducted was also interesting — entirely remotely and by mailing drugs to patients.

The last study I'll briefly mention was presented as a late-breaker, the ACTIV-1 IM study, that looked at whether two anti-inflammatory agents might enhance recovery. The drugs that were examined were infliximab and abatacept. Abatacept is a drug that is FDA-approved for rheumatoid arthritis and it works a bit differently. It's a selective T-cell co-stimulatory modifier. Of course, many of you are aware of infliximab, which has been around for a while as a tumor necrosis factor (TNF) inhibitor.

The primary endpoint was time to recovery. In this case, both arms were not significant, but on secondary analysis had reduced 28- and 60-day mortality for infliximab. Abatacept also reduced 28-day mortality but did not reach the primary endpoint of reducing time to recovery, being just barely off statistical significance with a P value of.057.

There has been perhaps some consideration as to where these drugs might fit in the same way as the better-studied baricitinib and tocilizumab. These are intriguing, but at this late stage I don't think there's much added. Because we have faced occasional drug shortages, and of course, with some of these newer variants that are emerging, we do worry whether we may be in circumstances such as during the early Omicron or Delta waves, when we saw a greater severity of illness.

This, of course, remains unknown, but I think it's helpful to be aware of information and potential alternatives in this regard. Thanks so much for listening.

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