Editor-in-Chief Peggy Peck offers some thoughts about celebrating before all the facts are known

The stock market loves good news, and in the midst of a pandemic, what news could be better than that of an effective treatment?

Apparently nothing, as evidenced by gains in the Dow Jones, NASDAQ, S&P 500, NYSE, etc., on word that remdesivir, a novel agent from Gilead Sciences, appears to be an effective treatment for severe Covid-19 symptoms.

But the “good” news comes not from published findings of an RCT but rather from this report in STATa well-written, nicely sourced report that was based on the transcript of a video discussion among clinicians at the University of Chicago, where 125 Covid-19 patients are receiving daily remdesivir infusions as part of an FDA-sanctioned phase III trial of the drug.

The article includes this transcript quote from Kathleen Mullane, DO, PharmD, who is described as PI for the trial: “The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish.”

In early January, FierceBiotech pointed out that Gilead was well-positioned to move rapidly with remdesivir, which was initially developed in conjunction with the CDC as a potential treatment for Ebola. That “R&D program culminated in a randomized controlled clinical trial that tested remdesivir and three other drugs in patients with Ebola.

“The trial found two of the drugs were more effective than remdesivir, putting an end to efforts to establish the NUC inhibitor as a treatment option in Ebola,” they wrote.

The case for remdesivir to treat SARS-CoV infection was detailed by Agostini et al in mBio in 2018, who wrote that remdesiver —also known as GS-5734— had potential to treat MERS-CoV and had “potential utility in the broad-spectrum treatment of CoV infections.”

But Gilead is cautious. An open letter from Gilead chairman and CEO Daniel O’Day, posted on April 10—6 days ahead of the STAT article—stated: “In studying remdesivir, the question is not just whether it is safe and effective against Covid-19 but in which patients it shows activity, how long should they receive treatment and at what stage of their disease would treatment be most beneficial. Many answers are needed, which is why we need multiple types of studies involving many types of patients.”

There are 152 clinical centers participating in a trial of severely ill patients that is planned for an enrollment of 2,400, and 169 clinical centers enrolling a total of 1,600 moderately ill patients. The trials are testing 10-day and 5-day treatment regimens. There are no control arms in the studies.

So when the results are “locked down” and results are released — most likely as topline results from the company, but eventually as peer-reviewed papers in medical journals — what will we know?

The lack of a control arm is a potential problem.

For example, consider SARS, the coronavirus that first alarmed the world.

A review published in 2007 noted that the SARS “pandemic caught the world by surprise in 2003 and spread rapidly within a relatively short period of time. Hence, randomized placebo-controlled clinical trials on the treatment of SARS were not possible. Our understanding was obtained from observational, cohort studies, case series and reports… Early in the pandemic, a combination of ribavirin and corticosteroids was adopted as the standard treatment in Hong Kong, Canada, and elsewhere because of the apparent good results of the first few patients. Subsequent reports showed that ribavirin was associated with a high rate of toxicity and lacked in vitro antiviral effect on SARS-coronavirus (SAR-CoV).” [Emphasis added].

And, of course, confusion about promotion of unproven treatments is already an issue in the current pandemic. For example, early studies of hydroxycloroquine (HCQ) offered evidence of benefit, but those early reports have not withstood scrutiny, so much so that the publishers of an French study that is often cited by HCQ believers had this to say about it:

“ISAC shares the concerns regarding the above article published recently in the International Journal of Antimicrobial Agents (IJAA). The ISAC Board believes the article does not meet the Society’s expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety.”

Of course, randomized trials of HCQ are now underway and, as with the clinical trials of remdesivir, there is more to come. But will that news be good? Stay tuned.

Peggy Peck, Editor-in-Chief, BreakingMED™

Cat ID: 125

Topic ID: 79,125,730,933,125,190,520,926,192,927,151,928,925,934