It’s great to see one of the region’s leading medical institutions partner with a private company on a possible preventive treatment for the novel coronavirus. It’s even better when the clinical trial is funded by a local nonprofit.
Afif Ghannoum was running Oasis Consumer Healthcare, a Cleveland-based manufacturer of oral-care products, when he made an observation that would change the trajectory of his entrepreneurial career: There wasn’t a single product on the market that offered long-lasting protection against airborne germs that entered the body through the mouth.
The Moreland Hills resident, a biotech attorney at BakerHostetler before he left to start Oasis 13 years ago, put his regulatory expertise to work. He and Brian Sokol, a partner with a background in specialty chemicals, began developing what he calls “a hand sanitizer for your mouth,” something that would coat the mouth and create a barrier that remained in place for hours.
“The problem with airborne germs is they hang in the air,” he says. “If you kill them instantly, that doesn’t really help you because [with] your next breath, they’re going to be right back in.”
He points out that moving into another space after someone coughs or sneezes isn’t always feasible, even in a time of social distancing.
The result, an oral spray sold over the counter under the name Halo, began appearing on retailers’ shelves in 2012 and spawned Cleveland-based ARMS Pharmaceutical a year later. Now, ARMS Pharmaceutical is navigating the Food and Drug Administration’s regulatory process for launching a major clinical trial on Halo as a new investigational drug — in this case, to determine whether the spray prevents front-line health care workers from becoming infected by the novel coronavirus, along with whether it decreases the frequency, duration and severity of symptoms in those who do develop the resulting upper-respiratory illness, COVID-19.
“More recent studies have verified that this virus especially invades not just the nasal mucosa — that’s the site for testing as to whether or not somebody has COVID-19 — but also the oral pharynx,” says principal investigator Dr. Robert Salata, chairman of the department of medicine at University Hospitals (UH) Cleveland Medical Center, program director of the UH Roe Green Center for Travel Medicine & Global Health, and professor of medicine, epidemiology and international health at Case Western Reserve University.
The 12-week study will involve approximately 3,700 nurses, doctors, respiratory therapists, physical therapists, etc. — 1,500 from University Hospitals. The rest are divided between MetroHealth Medical Center and Summa Health to ensure “a broader northeastern Ohio population of health care workers,” according to Salata. They will pursue the study with an IND exemption after hearing back from the FDA. It could start by mid-August.
“We really feel strongly that this will work,” he says.
The active ingredient in the spray, referred to clinically as ARMS-1, is cetylpyridinium chloride, or CPC, a common antiseptic found in several mouthwashes. Salata notes that a Chinese study published in a 2019 issue of the Journal of Virology found that it was effective in killing other coronaviruses, including those that cause the potentially fatal severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).
What sets ARMS-1 apart from other oral products is its infusion of CPC in a berry-flavored preparation of xanthan gum and glycerin, among other things. The user sprays his or her mouth three times with the patented formula, then swallows.
“What we believe happens is that it sticks to the back of the oral cavity,” Ghannoum says. “It kills germs that are there. But then, as more germs come in, they hit that barrier, and they stick.”
Tests in which ARMS-1 was mixed with a dye showed it spread around subjects’ mouths and remained there for up to six hours, even after they ate and drank. It can be used up to three times a day. And unlike “swish-and-spit” mouthwashes and rinses, it’s ingestible.
ARMS-1 already has shown promise in preventing influenza and other respiratory illnesses. In a small, three-month clinical trial funded by ARMS Pharmaceutical that Salata supervised at University Hospitals during the 2015-2016 cold-and-flu season, only six of the 94 healthy adult participants developed an upper-respiratory infection, a relative reduction of 55 percent.
“There was statistical significance around the ability to reduce symptoms, such as length of cough, severity of cough, sore throat, those types of things,” Ghannoum adds.
A 2017-2018 UH study involving approximately 60 bone-marrow transplant patients conducted to determine whether ARMS-1 was safe to give to that population provided similar results.
“Those folks often acquire, once they’ve been hospitalized for their transplant, these very resistant bacterial infections,” explains Salata, who also served as principal investigator on that trial. “That first is evident in the gastrointestinal tract and even in the mouth. We did not see the emergence of these very resistant bacteria in their mouth, at least, through that period of time.”
The initial collaboration between ARMS Pharmaceutical and UH resulted from a working relationship Salata and Ghannoum’s father Dr. Mahmoud Ghannoum, a director of medical mycology at Case Western Reserve University who also serves as ARMS’s chief scientific officer, had maintained for years. Salata had been intrigued by ARMS-1 when it first hit the market as Halo.
“When we approached UH about doing a clinical trial, it made sense to do it with him because of his expertise,” the younger Ghannoum says of Salata. “When all hell broke loose in March, [ARMS-1] was identified pretty quickly as a candidate that was worth studying. [The trial] was an amalgamation of UH’s leadership, my father, Dr. Salata all sort of putting the pedal to the metal and saying, ‘We should do this.’”
Talks with Ronn Richard, Cleveland Foundation president and chief executive officer, and his team yielded a $1 million grant to support the trial. According to Salata, it is only the second time in the foundation’s history that it has given money to fund a clinical trial.
“When this came up and they saw the tremendous potential impact it could have, they thought it was a great thing for their foundation to be involved in supporting,” Ghannoum says.
Halo, most recently sold on amazon.com for between $12.99 and $14.99 for a 1-ounce bottle, has not been available to the public since approximately March 23.
“The company, in preparation for this trial, pulled all their current stock off the market,” Salata says.
Production has ramped up at a contracted manufacturer in Aurora. Salata says there are preliminary talks of developing a nasal preparation and more ARMS-1 trials involving populations more vulnerable to developing COVID-19 and its severe complications: the elderly, nursing-home residents, those with hypertension and cardiac and lung disease and patients with cancer.
“[A vaccine] is our best hope for prevention in the future,” he observes. “But until we get there, particularly in our attempt to maintain our health care workforce, this, I think, is a very exciting way, a very safe way, to study this carefully and see if it makes a difference.”