As companies scramble to develop diagnostic tests and vaccines for COVID-19, there is a need for effective treatments for patients suffering severe respiratory effects from the novel coronavirus. To that end, Beyond Air Inc., of Garden City, N.Y., and Rehovot, Israel, has applied to the U.S. FDA to conduct an IDE trial of its inhaled nitric oxide (NO) system, Lungfit Bro, in COVID-19 patients.

The company plans to evaluate the Lungfit Bro in a randomized, open-label study of 75 adults with confirmed COVID-19 who require hospitalization. Patients will be randomized 2:1 and receive 150 ppm of NO for 40 minutes, four times a day, plus standard care or standard care alone. The primary efficacy endpoint is clinical improvement based on metrics such as fever and oxygen support. Additional endpoints include decreased viral load, cessation of fever, oxygen support, hospital length of stay, mechanical ventilation, death and various biomarkers, the company said.

FDA responses to IDE submissions typically occur within 30 days of filing.

“There is a mounting body of evidence that inhaled NO, including NO generated and delivered by our Lungfit Bro system, is safe and well-tolerated in animals and in human subjects at concentrations of 150 ppm and higher,” said Steve Lisi, Beyond Air’s CEO. “In vitro evidence points to inhibition of viral replication in a variety of viruses, including coronaviruses, as well as anti-inflammatory properties of nitric oxide.”

Earlier studies support NO benefits

Indeed, in a randomized, double-blind, placebo-controlled study in 2014 to compare NO plus standard care vs. standard care alone in bronchiolitis patients, four of 43 patients tested positive for coronavirus – two in the treatment arm and two controls. The length of stay for the two patients in the treatment group was 30 days, compared with 60 days for the two in the control group.

Efficacy data from two other bronchiolitis studies show about a one-day drop in length of stay. The company expects to report data from a third study this spring.

Beyond Air said neither its studies nor other high-concentration NO studies have shown any NO-related serious adverse events in more than 2,000 doses to more than 100 patients.

“We believe that our Lungfit Bro system may, given the three completed pilot clinical studies in bronchiolitis, be a significant tool in the battle against this coronavirus that has reached global pandemic status,” Lisi said. “In response to the unprecedented nature of the COVID-19 situation, Beyond Air is taking all necessary steps to make this potential solution available as quickly as possible to ensure that clinicians have access to NO therapy as a treatment option.”

Portable and easy to use

In an interview with BioWorld, Lisi said the study could likely be done in four to eight weeks, once the FDA gives the greenlight and preparations at clinical sites are completed. Bronchiolitis studies with Lungfit Bro have shown that up to five days of treatment is effective in infants, and the company expects a similar time frame for COVID-19. “We would expect it’s going to be the same thing, but maybe it will be a little longer, given the situation. We don’t know. But it’s not going to be three months,” he said.

Lisi said the regulatory pathway will be a PMA, as there is no precedent for the treatment, but declined to estimate a timeline for approval.

The 20-pound, portable Lungfit Bro system is designed to handle up to 240 volts and run off an electrical outlet. Because NO is generated from ambient air, the supply is unlimited. Special features include a rear port for supplemental oxygen, if needed by the patient, and disposable filters to remove nitrogen dioxide, which can build up with high concentration NO.

It’s also easy to use, meaning patients can self-administer the 40-minute treatments four times daily, and clinicians can simultaneously manage at least 10 systems with four patients each. A programming chip in the filter frees respiratory therapists from having to constantly reset the machines, while alarms monitor performance. Patients use individual breathing circuits to avoid contamination.

Lisi said Beyond Air has enough systems, filters and money to conduct the proposed IDE trial, even if the FDA asked it to double the size of the study. Once approved, the company could quickly produce “thousands and tens of thousands of systems and be “ready to go in six to eight weeks. The main system is manufactured for Beyond Air by Spartan Corp., of Minneapolis. A second contract manufacturer, which the company has not named, makes the filters for Lungfit Bro.

Second study being vetted

Beyond Air is considering a second trial to assess the use of Lungfit Bro in preventing infection in patients exposed to SARS-CoV-2, the coronavirus that causes COVID-19. Such a prophylactic treatment, if effective, could shorten quarantine times for people exposed to the virus, protect health professionals treated COVID-19 patients and aid the military in troop logistics.

The company has applied to HHS’ Biomedical Advance Research and Development Authority (BARDA) for grants to support its COVID-19 efforts with Lungfit Bro and build high capacity to manufacture Lungfit Bro systems at scale.

Laidlaw & Co.’s Yale Jen gave Beyond Air a thumbs up. “We view this is good news that exhibits a quick and decisive move by XAIR to help and deal with the most typical and urgent problem the world is facing right now, especially given the well validated MOA of NO as an anti-viral modality,” he wrote. “We also believe the virus is less likely to develop resistance toward NO versus other chemistry-based therapies.”

Responding to a ‘needs market’

During a March conference call, Lisi underscored that COVID-19 is a priority matter. It “could be something that takes some attention away and maybe some things get pushed out a little – not the pulmonary hypertension approval, not the bronchiolitis pivotal,” he said, referring to two other Lungfit Bro programs. “Don’t get me wrong, but COPD and oncology can certainly slip if we have to focus on COVID-19.”

Lisi described COVID-19 as more of a “needs market” than a commercial market, noting bronchiolitis approval could take about two and half years, people want treatments for COVID-19 now. “I think that if you run an open-label study in COVID-19 patients and … this works and it’s safe, and they give us approval, we’re ready to go,” he said on the call.

Mallinckrodt plc is also seeking to leverage NO in the fight against COVID-19. Last week, the Staines-upon-Thames, U.K.-based company reported that it was in early talks with the FDA about an investigational new drug (IND) study of its INOmax inhaled gas in patients with coronavirus-associated acute respiratory distress syndrome. In a very small study of patients with SARS-COV, INOmax was found to improve oxygenation and reduce the need for supplemental oxygen and ventilator support.