RLF-100 Drug Could Speed Up Recovery of Critically-Ill COVID-19 Patients
Wed, April 21, 2021

RLF-100 Drug Could Speed Up Recovery of Critically-Ill COVID-19 Patients



A new drug developed by two firms found to rapidly improve symptoms of critically-ill COVID-19 patients. The drug could significantly hasten the recovery of patients who developed respiratory failure.

A new drug called RLF-100 has been found effective in COVID-19 patients who experienced acute respiratory distress syndrome (ARDS). Although its general safety and efficacy are being determined in clinical trials, doctors in a hospital administered it to some patients who showed indications. Those patients recovered from ARDS as quickly as four days, which removed the need for mechanical ventilation. The drug is developed by Relief Therapeutic in partnership with NeuroRx.



Acute Respiratory Distress Syndrome in COVID-19

SARS-CoV-2, the virus of COVID-19, primarily attacks cells in the respiratory system. The more cells are infected, the more damage is done in the lungs. And the longer the illness is, the higher the risk of severe outcomes. Serious outcomes of COVID-19 include breathing difficulty, systemic inflammation, and respiratory failure. As such, patients with moderate to serious symptoms are recommended to be treated and monitored in medical facilities.

According to Relief Therapeutics, a biotechnology firm, ARDS is a life-threatening complication of COVID-19. The condition is characterized by rapid, widespread inflammation in the lungs. It is usually linked to multi-organ system failure, which may lead to premature death. In COVID-19, the virus can induce two connected events inside the lungs.

First, the virus can infect type 2 alveolar cells by binding to the ACE2 receptor protein. These cells play a role in secreting fatty substances and proteins to prevent alveoli collapse. But the pathogen destroys cells after making new copies, promoting alveoli collapse. It explains improper lung function.



And second, the occupancy of ACE2 by SARS-CoV-2 changes cellular processes. The occupancy increases blood pressure and promotes cytokine production. Inflammatory cytokines at very high levels can induce a cytokine storm – a type of widespread inflammation. Because of the inflammation, fluids in the lungs accumulate which may lead to edema.

Unfortunately, there is no cure for ARDS. Clinicians typically provide supportive care, such as intubation and mechanical ventilation, and wait till the lungs heal from injury or infection. In a paper published in The Lancet journal, on July 6, 2020, COVID-19 surged the number of ARDS patients. Authors examined the respiratory support in those patients. Seven studies were analyzed for what type of support was given.

All of the 16 patients in a study in Italy were given invasive mechanical ventilation (IV). While in another study in Italy with 1,300 patients, 1,150 were given IV and 137 were given non-invasive ventilation (NIV). Out of 24 patients in a study in Seattle, 18 were given IV and 10 were given high-flow nasal cannula (HFNC), a simpler oxygen therapy than NIV. In a Boston study, all 66 patients were given IV but one patient had both IV and NIV, and another patient had both IV and HFNC.

In the Amsterdam study, all 38 patients received IV. Two studies in New York City showed the majority of patients under IV. One study had 257 patients and 203 were treated with IV, three with NIV, and 12 with HFNC. The other study had 267 patients and all of them were treated with IV. A total of 51 of 267 patients were also treated with NIV. The authors showed that some patients had to be administered with more than one respiratory support type.



Aviptadil for COVID-19-Related ARDS

Two firms have developed a drug that addresses the root causes of lung inflammation linked to COVID-19. The RLF-100 or Aviptadil is a synthetic version of a natural peptide. While it is currently being investigated for erectile dysfunction, both firms see the potential in treating critically-ill COVID-19 patients. Its vasoactivity could reduce the inflammation caused by SARS-CoV-2 in the lungs.

"No other antiviral agent has demonstrated rapid recovery from viral infection and demonstrated laboratory inhibition of viral replication," said Jonathan Javitt, CEO of NeuroRx, quoted international news organization Reuters.

RLF-100 proved its potential in a 54-year-old male who developed COVID-19 while under treatment for double lung transplant rejection. Since the drug's indication include ARDS, doctors at Houston Methodist Hospital considered it for the patient. Under emergency use, doctors administered the patient and observed their symptoms. In four days, the patient's breathing condition improved and doctors had to remove the ventilator. The same outcome was observed in 15 other patients qualified for the drug.

The emergency use for the drug is permitted via the Fast Track designation of the US Food and Drug Administration. Early findings revealed its potential in treating respiratory distress due to COVID-19. However, it cannot be used yet for every COVID-19 patient with breathing problems. The drug's indications are limited to ARDS, COVID-19 ARDS, and sarcoidosis.

To further expand its utilization in COVID-19 cases, the firms started two Phase IIb/III studies of aviptadil. The first study involves patients with COVID-19-induced ARDS admitted to intensive care units. Patients are either given endotracheal intubation, mechanical ventilation, or other similar procedures to support breathing. They have been randomly assigned to receive either placebo shots or aviptadil, with doses from 50 to 150 picomole per kilogram per hour for 12 hours. Investigators will look into mortality at five days with a follow-up of 30 days.

The other trial focuses on non-acute lung injury due to COVID-19. Patients involve demonstrated reduced blood oxygenation, dyspnea, and exercise tolerance without respiratory supportive care. Patients are to receive either inhalable aviptadil, standard inhalation therapy, or placebos three times per day. Investigators will examine progression to ARDS in 28 days.

Meanwhile, independent researchers in Brazil highlighted the effects of RLF-100 in lab settings. They said that the drug could block the replication of SARS-CoV-2 in human immune and lung cells. The disrupted replication reduced the number of infected lung cells and promoted lung recovery during infection.

ARDS is a challenging health complication due to the lack of cure. Supportive care also depends on the severity of the condition. One way to effectively assist patients is to apply evidence-based guidance that permits adjustments to meet patient-specific issues.