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A proprietary formulation of vasoactive intestinal peptide (VIP) called RLF-100 (a.k.a. aviptadil) might have helped critically ill COVID-19 patients, although initial results remain to be confirmed in well-designed trials.

If the product does succeed, it would complete a 50-year effort to bring VIP into the clinic as a drug.

In their press release last week, Wilmington, Delaware-based NeuroRx and Relief Therapeutics AG of Switzerland described rapid recovery of a seriously ill patient, age 54, who received RLF-100 at Houston Methodist Hospital. The man developed COVID-19 following a double lung transplant. He was able to come off the ventilator the day after completing a 3-day series of RLF-100 infusions. Clinicians at Houston Methodist, along with NeuroRx CEO Jonathan Javitt, also wrote up the case .

"Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol," NeuroRx and Relief Therapeutics said. These patients received the drug as compassionate use after being deemed too sick to participate in the companies' , according to the release. As such, there was no control group.

Findings in those patients, according to the companies, included rapid clearing of "classic pneumonitis findings on an x-ray," improvement in blood oxygen, and a 50% or greater average decrease in laboratory markers associated with COVID-19 inflammation.

VIP was first by , and Viktor Mutt; it was found to have , especially in the lung.

Said, who died in 2013, "was an enormous proponent of VIP and was looking for a clinical applications for most of his life after the discovery," according to a former colleague, Nicholas Hill, MD, of Tufts Medical Center.

That eventually led to aviptadil. It was initially thought to have application in pulmonary hypertension and acute respiratory distress syndrome (ARDS). But after eight patients showed a "miraculous response," said Hill, subsequent trials were . That was in the early 2000s.

"The drug lay there ... all dressed up with nowhere to go," he noted.

Hill explained how the drug might have application in COVID-19, as the virus "appears to damage blood vessels in very severe cases."

"VIP might preserve vessel function if damaged by COVID. There are a lot of receptors on cells in the lungs that could be infected by COVID and perhaps [RLF-100] could prevent uptake of virus into these cells and stop the progression of disease."

Despite its failures in pulmonary hypertension, Hill said its properties still mean it could be useful in a number of ways in COVID-19 patients.

"If one of the mechanisms turns out it can prevent uptake of the virus, it could be used as a preventative. It could potentially be used in people just getting sick," he said. "Any drug that could do that, you would want to use early, late, whenever the situation arose."

But Hill cautioned it's still extremely early in the process, and warned other drugs have "gone this route before. Things look great when you give it to the first few patients [but] don't look so great when you get a study put together."

NeuroRx's trials for a variety of patients with COVID-19. Hill said he would not consider what he has seen so far as "real data," but added that "it's nice to have something that looks promising." A is also reportedly underway.

"I am cheering for Sami Said, because if somewhere out there, he knew his drug could block the progression of COVID, there wouldn't be a happier man in the world," Hill said.

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