RLF-100 (Aviptadil) Associated with Rapid Respiratory Failure Recovery Among COVID-19 Patients

Aug 3, 2020 | COVID-19, News, Popular Posts, Positive Results, RLF-100, SARS-CoV-2

RLF-100 (Aviptadil) Associated with Rapid Respiratory Failure Recovery Among COVID-19 Patients

NeuroRX, Inc. and Relief Therapeutics Holdings AG (SIX:RFL, OTC:RLFTF) “Relief” announced that the investigational therapy RLF-100 (Aviptadil) evidence rapid recovery from respiratory failure in the most critically ill patients with COVID-19. In parallel, an independent group of researchers have reported that Aviptadil blocked replication of SARS-CoV-2 in human lung cells and monocytes. The drug has been granted Fast Track designation by FDA and is being developed as a Material Threat Medical Countermeasure in cooperation with the National Institutes of Health and other federal agencies.

First Use Emergency Use IND Houston Methodist Hospital

The first report of rapid clinical recovery under emergency use IND was posted by doctors from Houston Methodist Hospital. The report describes a 54-year-old man who developed COVID-19 while being treated for rejection of a double lung transplant and who came off a ventilator within four days. Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol which is open to patients too ill to be admitted to the ongoing Phase 2/3 FDA trial.

Positive Findings Continue

Patients with Critical COVID-19 were seen to have a rapid clearing of classic pneumonitis findings on x-ray, accompanied by an improvement in blood oxygen and a 50% or greater average decrease in laboratory markers associated with COVID-19 inflammation

The clinical findings may be based on evidence that VIP inhibits the replication of the SARS-CoV-2 virus in human lung cells and immune cells (monocytes).  The work was reported by Brazilian researchers working in a level-4 biocontainment laboratory. The same researchers reported a case-control study in which patients who survived being on ventilators for COVID-19 had significantly higher levels of VIP in their blood than those who died of respiratory failure.

“No other antiviral agent has demonstrated rapid recovery from viral infection and demonstrated laboratory inhibition of viral replication,” said Prof. Jonathan Javitt, CEO and Chairman of NeuroRx. “We are conducting placebo-controlled trials to see whether the observations made in the case-control and open-label studies will be confirmed for less ill patients with COVID-19-related respiratory failure. Our independent Data Monitoring Committee will be conducting an interim analysis of these data later this month.”

About VIP in Lung Injury

Vasoactive Intestinal Polypeptide (VIP) was first discovered by the late Dr. Sami Said in 1970. Although first identified in the intestinal tract, VIP is now known to be produced throughout the body and to be primarily concentrated in the lungs. VIP has been shown in more than 100 peer-reviewed studies to have potent anti-inflammatory/anti-cytokine activity in animal models of respiratory distress, acute lung injury, and inflammation. Most importantly, 70% of the VIP in the body is bound to a rare cell in the lung, the Alveolar Type II cell, which is critical for the transmission of oxygen to the body.  VIP has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, pulmonary fibrosis, asthma/allergy, and pulmonary hypertension.

COVID-19-related death is primarily caused by respiratory failure. Before this acute phase, however, there is evidence of early viral infection of the alveolar type 2 cells. These cells are known to have angiotensin converting enzyme 2 (ACE2) receptors at high levels, which serve as the route of entry for the SARS-CoV-2 into the cells. coronaviruses are shown to replicate in alveolar type 2 cells, but not in the more numerous type 1 cells. These same type 2 alveolar cells have high concentrations of VIP receptors on their cell surfaces giving rise to the hypothesis that VIP could specifically protect these cells from injury.

Injury to the type 2 alveolar cells is an increasingly plausible mechanism of COVID-19 disease progression. (Mason 2020). These specialized cells replenish the more common type 1 cells that line the lungs. More importantly, type 2 cells manufacture surfactant that coats the lung and is essential for oxygen exchange. Other than RLF-100, no currently proposed treatments for COVID-19 specifically target these vulnerable type 2 cells.

About RLF-100

RLF-100 (aviptadil) is a patented formulation of Vasoactive Intestinal Polypeptide (VIP) that was developed based on Dr. Said’s original work and was originally approved for human trials by the FDA in 2001 and the European Medicines Agency in 2005. VIP is known to be highly concentrated in the lungs and to inhibit a variety of inflammatory cytokines. Relief’s predecessor company, Mondo Biotech, was awarded Orphan Drug Designation in 2001 by the U.S. FDA for aviptadil in the treatment of Acute Respiratory Distress Syndrome and in 2005 for treatment of Pulmonary Arterial Hypertension. Mondo was awarded Orphan Drug Designation by the European Medicines Agency in 2006 for the treatment of acute lung injury and in 2007 for the treatment of sarcoidosis. Both the U.S. FDA and the EMEA have granted Investigational New Drug licenses for human trials of aviptadil.

About RELIEF THERAPEUTICS Holding AG

The Relief group of companies focus primarily on clinical-stage projects based on molecules of natural origin (peptides and proteins) with a history of clinical testing and use in human patients or a strong scientific rationale. Currently, Relief is concentrating its efforts on developing new treatments for respiratory disease indications.

Relief Therapeutics holds orphan drug designations from the U.S. Food and Drug Administration and the European Union for the use of VIP to treat ARDS, pulmonary hypertension, and sarcoidosis. Relief Therapeutics also holds a U.S. patent for RLF-100 and proprietary manufacturing processes for its synthesis.

6 Comments

  1. Harvey Hechel MD

    If what you seem to be reporting is true why is data being held up. Thousands are dying everyday. If 15 critically ill patients really had a dramatic response to therapy then a letter to the editor of a major medical journal with the report of 15 cases should be published worldwide within 24 hours.

  2. Gary Richards

    Would it be useful for COPD as well?

    • TrialSite

      Dr. Barnes thanks for the visit.
      RFL-100 is showing promise! This candidate has been fast tracked by the FDA to treat respiratory distress associated with COVID19. The company (NeuroRX and the partner that actually owns the IP (Relief Therapeutics traded under the symbol RLF in Swiss exchange & RLFTF OTC) were requested to submit a publicly-available expanded access policy thereby allowing physicians to request RLF-100 for patients who are being treated in hospitals but not involved with the ongoing Phase 2/3 clinical trials. This means that its possible to get the drug now in certain circumstances.

      As it was awarded Fast Track Status in June what are the benefits:
      More frequent interaction with FDA which can accelerate timelines
      Accelerated approval or priority review
      Rolling review (this means the sponsor can submit sections of the New Drug Application (NDA) and expect review by the FDA rather than having to wait till the end and send the whole thing)
      There are two disclosed studies including a Phase 2 and a Phase 2/3 scheduled to conclude Sept 2020 and the other Nov 2020 and also the expansion protocol. The participating sites in the two studies include UCI (Richard Lee, MD, University of Miami, Miller School of Medicine (Dr. Jayaweera); University of Louisville (Dr. Lenhardt); and Houston Methodist (Dr. Youssef); NYU Langone (Dr. Daniel Sterman) and Rambam Health Care, Haifa, Israel (Dr. Bar-Lavie).

      A material piece of information was that on July 16 the companies reported that the study’s independent Data Monitoring Committee reviewed the findings from the first 30 patients treated in the Fast Track FDA trials of RLF-100 (Aviptadil) in those patients with COVID-19 respiratory failure and found that the study appeared capable of reaching a statistically significant endpoint within its 144 patient sample size. Consequently the IDMC voted to continue the study till the next eval period which would be four weeks (coming soon). FYI this committee is led by Professor Alfred Sommer, MD (Johns Hopkins); Professor Rita Colwell (former NSF director) and Andy Harris (dr. and former Congressman as well as part time prof. at Johns Hopkins).

      This drug could be approved sooner than later. When that is we couldn’t tell you but if there is clear and evident data that it works they could stop the study and proceed with the process. We could say that it is possible it goes directly into the approval process and available sometime in 2020. Of course this all is contingent on the positive data points continuing which isn’t necessarily a given.

      Probably not the exact answer you wanted but hopefully this is helpful.
      Best Regards,
      Publisher

  3. Rosie Shappa

    My husband is 50 years old. He is currently at NE Baptist Hospital in San Antonio, TX. He contracted COVID and has been in the hospital for 12 days now. He was given Remdesivir. He has been on a ventilator for 12 days and is currently on the max settings. Obviously his lungs are the primary concern. I requested they give him RFL-100. The hospitals infectious disease doctor said he is running into a lot of “red tape” and unable to get it. I really think this drug could help him but how do I go about getting it for my husband?

  4. Andrea Perez

    My mother who is 56 years old has been on the ventilator since July 15,2020 in Houston Texas Memorial Hermann Southeast she initially had convalescent plasma and has still been having issues with her lungs. The ventilator setting has been at 100% since she’s been on it with a peep of 20 and the doctors have not been able to wean her off or even lower the settings. I have asked about this medication RFL-100 (Aviptadil) and was told she is a candidate for it the only problem is Memorial Hermann doesn’t have it and was also told there is a lot of red tape to get it. My moms lung doctor is willing to give it to her as well if only he had a way to get it for her.This is heartbreaking since Methodist in Houston has it and they are merely 20-25 minutes away from the hospital she is currently at. If this medication can potentially save lives please get it to the hospitals that are willing to use it for there critically ill patients. I am desperate as she is young and is fighting for her life.

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