The promising COVID therapy for respiratory failure few have heard of, but will soon - NeuroRx and Relief Therapeutics RLF-100 (Aviptadil)

https://www.businesswire.com ^ | 08.05.2020 | Numerous

[rxsid]

UPDATE:

FDA grants inhaled use IND for RLF-100 (aviptadil) to treat patients with moderate and severe COVID-19 aiming to prevent progression to respiratory failure

• - Aviptadil is now shown as the first COVID therapeutic to block replication of the SARS-CoV-2 virus in human lung cells and monocytes, while also preventing synthesis of cytokines in the lung
• - RLF-100 is a patented formulation of aviptadil (synthetic human Vasoactive Intestinal Polypeptide, VIP), which has been granted FDA Fast Track Designation, FDA emergency use IND authorization, and an expanded access protocol

RADNOR, Pa. and GENEVA, Aug. 6, 2020 /PRNewswire/ -- NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTC:RLFTF) "Relief" today announced that NeuroRx has been granted Investigational New Drug (IND) permission to test RLF-100 (aviptadil) for inhaled use in patients with moderate and severe COVID-19 in order to prevent progression to respiratory failure.

The study is posted at https://clinicaltrials.gov/ct2/show/NCT04360096. The first phase will commence with patients hospitalized for severe COVID-19 who do not yet have respiratory failure. If promising results are seen in the inpatient setting, the trial will expand to patients at home with mild and moderate COVID-19 in order to prevent the need for hospital admission.

Professor Jonathan Javitt, MD, MPH, CEO of NeuroRx said, "Now that we know VIP suppresses replication of the SARS-CoV-2 virus in human lung cells, based on the outstanding work of the Oswaldo Cruz Institute (Rio de Janeiro),1 we are optimistic that treatment with VIP will not only help patients on ventilators, but will help to stop the advancement of the virus in patients with earlier stages of COVID-19. By blocking cytokine synthesis in the lung cells and increasing the production of surfactant, which is key to the lung's ability to transmit oxygen, we are hopeful that inhaled VIP will prove to be of clinical benefit across a wider array of patients suffering respiratory complications from COVID-19 infection."

The clinical trial of the inhaled formulation of RLF-100 is expected to begin on or before September 1, 2020.

https://www.prnewswire.com/news-releases/fda-grants-inhaled-use-ind-for-rlf-100-aviptadil-to-treat-patients-with-moderate-and-severe-covid-19-aiming-to-prevent-progression-to-respiratory-failure-301107288.html

[rxsid]

Inhaled Aviptadil for the Treatment of Moderate and Severe COVID-19 (AVICOVID-2)

Study Description

Brief Summary:

SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care.

Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer.

The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

Detailed Description:

Attack of the Alveolar Type II (ATII) cell via its ACE2 surface receptor by the SARS-CoV-2 virus leads to respiratory failure, morbidity, and frequently mortality in COVID-19. There is no approved treatment that specifically targets the pulmonary injury. Vasoactive Intestinal Peptide (VIP) is known to target the VPAC1 receptor of the ATII cell and to protect that cell against all manner of injuries, including smoke inhalation, exposure to stomach acid, and exposure to infectious agents. VIP prevents apoptosis, blocks cytokines, lowers TNFα levels, reverses CD4/CD8 ratio, and reduces cough and dyspnea in nonclinical and clinical studies. Aviptadil, a synthetic form of Vasoactive Intestinal Polypeptide (VIP) has been awarded FDA Orphan Drug Designation for the treatment of ARDS and Pulmonary Hypertension and EMEA Orphan Drug Designation for the treatment of ARDS and Sarcoid. RLF-100 (Aviptadil) has been granted FDA Fast Track Designation for the treatment of ARDS/Acute Lung Injury in COVID-19.

The objective of this study is to identify patients with moderate and severe COVID-19 who have not yet developed respiratory failure and to treat them with inhaled Vasoactive Intestinal Polypeptide (VIP) in the hope of preventing progression to Critical COVID-19 with Respiratory Failure.

Nonclinical studies demonstrate that VIP is 70% concentrated in the lung, where it binds primarily to ATII cells. VIP prevents NMDA-induced caspase-3 activation in the lung, inhibits IL6 and TNFα production, protects against HCl-induced pulmonary edema, These and other effects have been observed in numerous animal model systems of lung injury in mice, rats, guinea pigs, sheep, swine, and dogs. In these models, Aviptadil restores barrier function at the endothelial/alveolar interface and thereby protects the lung and other organs from failure.

Both intravenous and inhalation preclinical toxicology and safety pharmacology have been performed in four species, with a six month trial of inhaled RLF-100 in primates.

Aviptadil is approved for human use in Europe and has a demonstrated 20 year history of safety in numerous trials for Sarcoid, Pulmonary Fibrosis, Bronchospasm, Erectile Dysfunction, and a phase I trial in ARDS. In that phase I trial, 8 patients with severe ARDS on mechanical ventilation were treated with ascending doses of VIP. Seven of the 8 patients were successfully extubated and were alive at the five day timepoint. Six left the hospital and one died of an unrelated cardiac event.

Five GCP phase 2 trials of RLF-100 have been conducted under European regulatory authority. Non GCP healthy volunteer studies have shown that i.v. infusion of Aviptadil is well tolerated with few adverse effects including alterations in blood pressure, heart rate, or ECG. In addition to published studies of human use, Aviptadil has been used on a compounded basis in certain ICUs for many years in the belief that it preserves life and restores function in pulmonary hypertension, ARDS, and Acute Lung Injury (ALI).

In this study, patients patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer.

The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

https://clinicaltrials.gov/ct2/show/NCT04360096

[rxsid]

The CEO of Relief Therapeutics, Dr. Raghuram Selvarju was on Fox Business earlier today regarding RLF-100 (Aviptadil):

Doctor hopeful inhaled version of drug can combat early-stage coronavirus

Note: The injectable form of RLF-100 is for Wuhan-19 patients who are in serious/critical condition to prevent respiratory failure...while the inhaled version is for earlier/mid disease stage.

Yes, I know, Cavuto is anti HCQ and at least a bit of an anti-Trumper.

[rxsid]

This is great news https://t.co/IQhjoL4mzT— Dr Drew (@drdrew) August 12, 2020

The video interview: Discussion with Dr. Jonathan Javitt about Aviptadil and Vasoactive Intestinal Peptide

[rxsid]

Dr Oz. mentioned Aviptadil on Fox News last March:

https://www.youtube.com/watch?v=vQ_mrOkZnbc&feature=youtu.be&t=385

[rxsid]

Story of Houston Fire Capt Tommy Searcy.

Two others from Houston Fire have died of Covid 19,

Third Houston firefighter in ICU with COVID-19 as department prepares for another's funeral, union president reports

Capt Searcy is in critical, worsening condition as of this morning when RLF-100 was rushed to the hospital where he in on a ventilator.

After late night approvals from docs at @memorialhermann and execs at @NeuroRxPharma, @FirefightersHOU raced experimental COVID medication RLF-100 to ailing @HoustonFire Capt Tommy Searcy under escort early this morning. 'Now, we pray,' union leader tells @abc13houston pic.twitter.com/wpvXUAyVMw— Ted Oberg (@TedABC13) August 18, 2020

His brother Tommy, also a Houston firefighter, rushed the compassionate use pick up of RLF-100 to the hospital with police escort.

https://www.facebook.com/tony.searcy.7/videos/10219524769290019/

Now that Aviptadil has gained more attention, this case will be one to watch in the coming days. If he is able to recover from such a grave condition, after being administered Aviptadil, expect to hear much more on this promising therapeutic.

[rxsid]

"Time's not on our side" HFD family hopes for experimental COVID drug
Tuesday, August 18, 2020 1:10PM

HOUSTON, Texas (KTRK) -- HFD veteran Tommy Searcy's condition is worsening inside an ICU room at Memorial Hermann Hospital in The Woodlands. Now his medical team may be running out of options.

The fire union tells ABC13 a ventilator is helping Searcy breathe while an ECMO machine scrubs his blood.

"It doesn't appear to be positive news," union president Marty Lancton said, "The word we're getting from his brother, Tony is that doctors are becoming worried, and that's never a good thing when someone is battling this virus."

Last week when he was moved to the ICU, the union asked for prayers for Searcy in a social media post.

Tonight, they are asking for more. Searcy's family, doctors and union leaders are all hoping for approval to use an experimental drug that has shown promise helping relieve COVID-19 symptoms in patients lungs and air sacs.

The drug, RLF-100 (Aviptadil) made by Neuro-RX, is not yet approved by the FDA. It is in a fast-track study at four hospitals nationwide and has "shown promise" according to the company.

The Houston Methodist Hospital is one of the sites, but Searcy is at Memorial Hermann. His doctors are racing against time and COVID-19's unrelenting grip to get approval before Searcy declines any more.

In a letter to the company Monday, the Houston Professional Firefighters Association asked the company for humanitarian access to the drug.

The company tells ABC13 it has already been in touch with Searcy's medical team and is awaiting final paperwork from Searcy's doctors. The process is not an easy one. Searcy's physician and Memorial Hermann have to sign off on its use before asking the company for the medication.

The company vows to get it as soon as the paperwork is completed.

"Right now, this is what he [Searcy] needs," Lancton said. "Time is not on our side. We just need to ensure we give Captain Searcy the best chance to fight this."

Pausing for a moment to reflect on a very difficult few weeks for the Houston Fire Department, Lancton was overcome, "We've already buried two firefighters. We don't want to bury a third."

UPDATE: HFD Captain Tommy Searcy's doctors received the experimental medicine early Tuesday morning. Searcy's doctors, family, Memorial Hermann hospital, Methodist Hospital and Neuro RX, the drug's manufacturer worked late into Monday evening to get final approvals.

Once the paperwork was approved, fire fighter's union leaders raced the medicine under emergency escort from the med center to The Woodlands, where Searcy is in Intensive Care.

"Now we pray," union president Marty Lancton told ABC13.

Dr. Jonathan C Javitt, Neuro RX's CEO & Chairman told ABC13 in a written statement, "Our team at NeuroRx is doing everything possible to make this drug available to the Searcy family. The FDA created an expanded access pathway specifically for these situations with the strong encouragement of Congress. All that is required is for the Institutional Review Board (IRB) of a qualified hospital to approve the use of an investigational medication according to the FDA approved protocol. Our hopes and prayers are with this firefighter and his family who are now fighting the toughest fire imaginable."

Captain Searcy is a 17 year HFD veteran. He is 45 years old and a father of three. His family said he had no underlying conditions.

[hawkaw]

I really hope this experimental therapy works.

[JerseyDvl]

The powers that be do not want anything released that will actually help people... Until 11/4.

[khelus]

Re: Please, please remember that ZINC is an essential part of the HCQ treatment. Most people with co-morbidities are likely low on zinc and zinc (and other vitamins like C & D3) are quickly used up when Covid strikes. Zinc is like the soldiers going into combat, and the ionophore action of HCQ is like the landing craft carrying Zinc soldiers into the combat zone (inside the infected cell). Below is the best article I have seen regarding development and need for early treatment and especially zinc. It has 22 references, mostly scientific.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202847/

It appears that the way Covid kills is by making people severely deficient in major nutrients like zinc, Vitamins C, D3, and possibly E. What HCQ does is function as an ionophore to allow zinc into cells to kill/stop the virus which is trying to reproduce. If given early, there are not so many viruses that they overwhelm all the body systems. I would say that Covid-19 and many other pathogens attack and destroy nutrients. Co-morbidities especially are nutrient deficiency diseases. Self neglect is the crime, Covid is the executioner.

The cure is provide something that will attack Covid quickly before everything is depleted, and at the same time restore large amounts of the nutrients that are most critical. A few individual nutrients are being studied such as Vitamin C, but the interaction is complex and clinical trials are rarely set up for complexities. A hundred years of Allopathic medicine (drugs and surgery) have exceeded what they are good at. Now is the time for Natural Medicine to show what it can do. Dr. Zelenko’s protocol using early treatment, zinc, an ionophore, and an antibiotic seems quite effective. And it only costs $20 for 5 days. A good mix of vitamin and mineral supplements can be supplied for $1 a day. The new darling of the drug company world appears to be Remdesivir which it is suggested will cost from $1,000 to $4,000. Price not yet decided on.

***
Excellent points. Also Doctors have been using existing generic steriods such as nebulized Budesonide with good results.

Dr. Zelenko has modified his protocol to add steriods and blood thinners on an outpatient basis when he feels it is warranted.

There is a very strong negative correlation between seriousness of the Wuhan Flu and vitamin D levels.

[rxsid]

Update on the testing going on at Houston Methodist Hospital (site) / Johns Hopkins University (contributor)

This is a "preprint" of the to-be officially released report on that study in Texas. Very, very encouraging:

Rapid Recovery from COVID-19 Respiratory Failure with comorbidity in 21 patients treated with Vasoactive Intestinal Peptide

Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect Alveolar Type II cells by blocking replication of the SARS-CoV-2 virus, inhibiting cytokine synthesis, preventing cytopathy, and upregulating surfactant production. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation for treating Critical COVID-19 with Respiratory Failure and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial.

...

Results: Median patient follow-up time is 21 days. So far, 19 of 21 patients have survived. One death was due to COVID-related multisystem organ failure and the other to an underlying and unrelated encephalopathy. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in both lungs of 17 patients and in one lung of 2 patients.. A mean 292% increase in PaO2:FiO2 ratio was seen during the time patients were on ventilation. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 9 patients and ongoing improvement in 10. Seven patients were discharged from the hospital, 7 have been sent to intermediate acute care, and 5 require ongoing intensive care. Three of 5 patients on extracorporeal membrane oxygenation (ECMO) prior to treatment with VIP have been decannulated and two have been discharged to home. A 75% (95% CI±3%: P<.001) reduction in IL-6 was seen with corresponding decrease in C-reactive protein. A median 4 point reduction in the NIAID Ordinal Scale was observed (P<.01).

...

Radiographic evidence (figure 2) on all patients is included in the online supplementary material. In all cases, clearing of the “ground glass” parenchymal changes associated with COVID-19 pneumonitis was apparent and was noted by the radiologists who read the chest x-rays. Quantitative analysis of radiographic changes will be the subject of a future report

https://t.co/hR3vi4RLB9?amp=1

[rxsid]

the ^preprint^ is undergoing peer review & therefore not officially released yet.

[rxsid]

Looks like it's more and more likely that COVID-19 is indeed a "RANTES" disease. Some info...

Role of CCL5 (RANTES) in Viral Lung Disease (2006)
RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), Inflammation, Obesity, and the Metabolic Syndrome (2007)

RANTES explained by Dr. Yo (Ram Yogendra M.D., M.P.H.) in YouTube vid - COVID-19 Update USA : How RANTES Can Explain Coronavirus Symptoms

[rxsid]

Aviptadil getting more traction...

New drug being used for COVID-19 patients with respiratory failure

"Dr. Sohail Rao, the president of the DHR Health Institute for Research & Development, announced Tuesday that DHR will be using Aviptadil to help patients fight the virus."

Watch the video for full story.

https://www.krgv.com/news/new-drug-being-used-for-covid-19-patients-with-respiratory-failure/

DHR Health Institute for Research & Development is out of Edinburg, TX.

[gleeaikin]

Low D3 levels is one reason dark skinned blacks and Latinos are being hard hit. The sun produces vitamin D in oils on the skin, but it does not absorb into the body as quickly through darker pigmentation as it does through light skin. In Accomack County in Virginia, and mostly black and Latino chicken factory works were the most quickly and hard hit. The fact that they work indoors all day didn’t help either. Simply giving them 5000 IU or 125 mg. of D3 a day would be very helpful.

[musicman]

BTTT!!!

[khelus]

Re: Low D3 levels is one reason dark skinned blacks and Latinos are being hard hit. The sun produces vitamin D in oils on the skin, but it does not absorb into the body as quickly through darker pigmentation as it does through light skin. In Accomack County in Virginia, and mostly black and Latino chicken factory works were the most quickly and hard hit. The fact that they work indoors all day didn’t help either. Simply giving them 5000 IU or 125 mg. of D3 a day would be very helpful.

***
If our ‘public health’ official were truly interested in the health of the public, they would be using the MSM to spread this information.

I’d also bet most if not all nursing home residents are deficient in vitamin D.

What a simple, inexpensive, safe bit of prevention!

[rxsid]

Aviptadil (RLF-100) For COVID-19: 21 Patients With Severe Refractory COVID Showing Improvements!
https://www.youtube.com/watch?v=QFAZjwxYZwo

Great presentation of the latest study, by Dr. "Whiteboard."

 

Note: He also did a whiteboard presentation back in July regarding HCQ+Zn+Azith:

Triple Therapy Zn, HCQ, And Azithro: NEW STUDY Using Triple Therapy For Outpatient Early COVID-19!
https://www.youtube.com/watch?v=4eR0oV0Yqwo

[rxsid]

NeuroRx’s RLF-100: the key to treating and preventing Covid-19 respiratory failure? (08.26.2020)

[rxsid]

NeuroRx and Relief Therapeutics Establish Supply and Distribution Agreements for RLF-100™ (aviptadil)
Development partners establish supply chain agreements and order sufficient drug substance to treat 1 million patients