RLF-100 Expanded Access Program At Houston Methodist Hospital 9-Fold Increased Probability of Survival from Critical COVID-19

Oct 15, 2020 | Comorbidity, COVID-19, Houston Methodist, News, Popular Posts, RLF-100, SARS-CoV-2, Severe COVID-19

RLF-100 Expanded Access Program At Houston Methodist Hospital 9-Fold Increased Probability of Survival from Critical COVID-19

Patients with critical COVID-19 and respiratory failure treated with RLF-100™ (aviptadil) have a 9-fold increased probability of survival and recovery from respiratory failure than those patients only on the standard of care, reports Relief Therapeutics Holding AG (SIX: RLF, OTCQB: RLFTF) and NeuroRx, Inc. based on a recent summary of Expanded Access Protocol results from Houston Methodist Hospital. Thanks to the heroic work of Dr. Jihad Georges Youssef and team there in Houston, as well as this investigational drug, lives were saved. A separate randomized controlled Phase 2b/3 clinical trial, to be completed by November 2020, should offer more evidence whether RLF-100 exhibits the definitive results for FDA approval or emergency use authorization.  

The Challenge

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 are essential for oxygen exchange. Other than RLF-100™, no currently proposed treatments for COVID-19 specifically target these vulnerable type 2 cells

The Prospective Study

In an open-label prospective study involving 45 patients, 21 of them where admitted to an intensive care unit (ICU) with critical COVID-19 and respiratory failure and treated with RLF-100™ (aviptadil) as compared to 24 control patients treated in the same setting. All patients had severe comorbidities that rendered them ineligible for the ongoing randomized controlled Phase 2b/3 trial being conducted to ascertain safety and efficacy of RFL-100, and all patients were deteriorating despite treatment with approved therapies for COVID-19. This study (NCT04453839) was part of the Expanded Access Study

The Results

Overall, 81% of RFL-100 treated patients survived beyond 60 days, compared to 17% of control patients. Patients treated with RLF-100 demonstrated a 9-fold increased probability of survival and recovery from respiratory failure, with a high degree of statistical significance. The statistical analysis for this study was performed by Professor Phil Lavin, FASA, FRAPS of Boston Biostatistical Research Foundation.

Principal Investigator POV

Jihad Georges Youssef, MD led the study. The section chief of General Academic Pulmonary Medicine at the Houston Methodist Hospital reports, “We are encouraged by these initial results in highly comorbid patients with COVID-19 respiratory failure, and we are pleased that the majority of these patients have returned safely to their families. We look forward to the upcoming results of the randomized, double-blind, prospective trial in less severely comorbid patients for confirmation of these results.” Dr. Youssef serves as the Principal Investigator at Houston Methodist as well as national co-chair for the ongoing randomized controlled trial.

Nearer, Inc. Chief Grateful to Houston Methodist Hospital

NeuroRx Inc. maintains the U.S. intellectual property rights to RFL-100 (licensed from Relief Therapeutics). Their CEO Dr. Jonathan Javitt reported, “We are grateful to Dr. Youssef and to the Houston Methodist Hospital for having the courage to treat and study patients at this level of risk. The results suggest that there may be substantial hope to mitigate the attack of the coronavirus on the delicate cells that line the lung with a natural peptide that has been protecting the lung’s lining since humans first walked the early. While the number of patients treated at Houston Methodist is modest, the initial results in our nationwide expanded access program suggest similarly encouraging survival with RLF-100™. We continue to monitor treatment with RLT-100 in other hospitals.”

About VIP in Lung Injury

Vasoactive Intestinal Polypeptide (VIP) was first discovered by the late Prof. 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 2 cell, that is critical to 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.

About RLF-100™

RLF-100™ (aviptadil) is a formulation of Vasoactive Intestinal Polypeptide (VIP) that was developed based on Prof. Sami Said’s original work at Stony Brook University, for which Stony Brook was awarded an FDA Orphan Drug Designation in 2001. VIP is known to be highly concentrated in the lungs, where it inhibits coronavirus replication, blocks the formation of inflammatory cytokines, prevents cell death, and upregulates the production of surfactant. FDA has now granted IND authorization for intravenous and inhaled delivery of RLF-100™ for the treatment of COVID-19 and awarded Fast Track designation. RLF-100™ is being investigated in two placebo-controlled US Phase 2b/3 clinical trials in respiratory deficiency due to COVID-19. Since July 2020, more than 150 patients with Critical COVID-19 and Respiratory Failure have been treated with RLF-100™ under FDA-approved protocols. Information on the RLF-100™ Expanded Access program can be found here.

About RELIEF THERAPEUTICS Holding AG

Relief focuses primarily on clinical-stage programs 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 holds orphan drug designations from the U.S. FDA and the European Union for the use of VIP to treat ARDS, pulmonary hypertension, and sarcoidosis. Relief also holds a patent issued in the U.S. and multiple other countries covering potential formulations of RLF-100™.

RELIEF THERAPEUTICS Holding AG is listed on the SIX Swiss Exchange under the symbol RLF and quoted in the U.S. on the OTCQB under the symbol RLFTF.

About NeuroRx, Inc.

NeuroRx draws upon more than 100 years of collective drug development experience and is led by former senior executives of Johnson & Johnson, Eli Lilly, Pfizer, and AstraZeneca, PPD. In addition to its work on RLF-100™, NeuroRx has been awarded Breakthrough Therapy Designation and a Special Protocol Agreement to develop NRX-101 in suicidal bipolar depression and is currently in Phase 3 trials. Its executive team is led by Prof. Jonathan C. Javitt, MD, MPH, who has served as a health advisor to four Presidential administrations and worked on paradigm-changing drug development projects for Merck, Allergan, Pharmacia, Pfizer, Novartis, and Mannkind, together with Robert Besthof, MIM, who served as the Global Vice President (Commercial) for Pfizer’s Neuroscience and Pain Division. Its Board of Directors and Advisors includes Hon. Sherry Glied, former Assistant Secretary, U.S. Dept. of Health and Human Services; Mr. Chaim Hurvitz, former President of the Teva International Group; Lt. Gen. HR McMaster, the 23rd National Security Advisor; Wayne Pines, former Associate Commissioner of the U.S. Food and Drug Administration; Judge Abraham Sofaer; and Daniel Troy, former Chief Counsel, U.S. Food and Drug Administration.

Of course, these results may or may not be indicative of the results of future and larger clinical trials for RLF-100 for the treatment of COVID-19.  For full disclaimer from NeuroRx, see the link. 

Lead Research/Investigator

Jihad Georges Youssef, MD, Critical Care Medicine, Sleep Medicine, Pulmonology, Transplant Pulmonology

Call to ActionTrialSite will monitor the Phase 2b/3 clinical trial for updates. The Phase 2b/3 study (NCT04360096) concludes Nov. 2020. Sign up for TrialSite’s newsletter for updates.

Source: PR Newswire

3 Comments

  1. Walt

    This is good news for treatment. However is anyone else disturbed by the ethics of these kind of studies? It seems 10 or so people died because they were not given the therapy. We have more than enough statistical evidence on the probability of death for people with serious comorbitities to estimate the number of deaths without having to have a placebo group. This does not sit well with me. Studies of this design when used during a pandemic need to be reviewed. With results like those, why was the study not stopped and the placebo group also given this therapy?

    Reply
  2. Zaran Dunloy

    Great results for the gravely ill, let’s hope it has a rapid, safe, and efficacious clinical trial results soon As there is no other therapeutic worth speaking about.

    Reply
  3. Bill swanson

    If rlf100 is saving lives, why does the FDA continue to overlook the success…do you think this is all politics? With the big Pharms getting the publicity ?

    Reply

Submit a Comment

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Pin It on Pinterest