Erectile dysfunction drug aviptadil may also beat Covid-19

Erectile dysfunction drug aviptadil may also beat Covid-19, experts believe

  • Aviptadil has been fast-tracked into clinical trials in the US since June
  • Early results show patients have come off ventilators in three to four days 
  • The drug is a synthetic form of a natural peptide in the body called VIP 
  • It’s shown to prevent inflammation and stop replication of the virus in lung cells 

A drug used for erectile dysfunction has the potential to treat critically ill Covid-19 patients, scientists say. 

Aviptadil has been fast-tracked into clinical trials in the US after promising results. It’s branded as Invicorp in the UK but is not yet marketed in the states.

Almost 300 patients with moderate and severe bouts of coronavirus at five hospitals in the US will be given the drug, which they will inhale.  

It has already been authorised as an emergency drug by the FDA, meaning it can be given to patients outside of clinical trials.

Some 16 patients in the US came off ventilators or recovered from respiratory failure within four days of inhaling the drug, the drug manufacturers claim.

And doctors in Houston claim the drug helped one patient on the brink of death make a ‘rapid recovery’.    

The drug is a synthetic form of a natural peptide in the body called VIP that protects lung cells from injury by reducing inflammation.

Brazilian researchers have also shown the peptide can block the coronavirus from entering cells and replicating. 

Aviptadil, labelled as Invicorp in the UK as an impotence treatment, has been fast-tracked into clinical trials for Covid-19 in the US after promising signs

Aviptadil is combined with another ingredient called phentolamine for the treatment of erectile dysfunction. 

The two medications, when taken together, help blood flow in and out of the penis, causing it to stay firm.

The formula is injected directly into the tissue on the sides of the penis causing an erection around five minutes later.

Men can only get it on prescription, and once they are shown how to carry out the injection by a nurse they can do it themselves. 

When the Covid-19 pandemic struck, US-Israeli company NeuroRx Inc partnered with Swiss drug firm Relief to develop the drug in the US.

Relief Therapeutics Holdings and NeuroRx Inc, which own the drug, today said they had been granted permission to progress trials of aviptadil for the prevention of respiratory failure in Covid-19 patients.

The first part of the phase two and three trial, expected to begin before September, will involve hospitalised severe Covid-19 patients.

If promising results are seen, the trial will expand to patients at home with mild and moderate Covid-19 in order to prevent the need for hospitalisation, Relief said in a statement.

Aviptadil will be inhaled, rather than injected, so it is suitable both for home and hospital use. The inhalation allows the drug to reach deep into the lung tissue. 

Half the patients will receive aviptadil while the other half, randomly selected, will be given a placebo drug and ‘maximal intensive care’. 

Aviptadil has already been through clinical trials for ARDS — a life-threatening lung disease and known complication of Covid-19. 

According to Relief, seven out of eight patients with severe ARDS on mechanical ventilation showed substantial improvement with doses of VIP. 

Six ultimately left the hospital alive. One died of an unrelated cardiac event and it is not clear what happened to the seventh as the results are not published in a journal. 

US regulators at the Food and Drug Administration have already granted emergency use of aviptadil to treat Covid-19 patients. 

This allows doctors to give an experimental drug to a critically sick patient without the usual application process. 

NeuroRx and Relief have now said that aviptadil delivered quick recovery from respiratory failure in the most critically ill patients suffering from Covid-19.

The first report of rapid recovery under emergency use was posted by doctors from Houston Methodist Hospital on August 1 on the website PrePrints.

The patient had developed Covid-19 while being treated for rejection of a double lung transplant. Miraculously he came off a ventilator within four days. 

Similar results were subsequently seen in more than 15 patients treated under emergency use, Relief and NeuroRx have reported.

X-rays showed patients had a rapid clearing of classic pneumonitis, accompanied by an improvement in blood oxygen, showing the lungs were working to pump oxygen around the body again. 

But because only a very small amount of people have been treated with aviptadil, and the drug was not compared to a dummy drug, it cannot be said definitively that aviptadil actually improved the patients’ outcomes or if it was just chance.

But now, the companies are conducting a placebo-controlled trial across five US hospitals to try and confirm aviptadil is treating patients. 

Some 70 per cent of the VIP in the body is bound to specific cells in the lungs, called the alveolar type two cell.

These cells are critical for the transmission of oxygen to the body, so without them, respiratory failure occurs.

The cells are targeted by coronavirus because they are coated with ACE-2 receptors, which serve as the doorway of entry for the virus to replicate. 

The theory is that the synthetic VIP will bind to the lung cells and block SARS-CoV-2 — which causes Covid-19 — from doing the same.

Relief and NeuroRx said researchers in at the Oswaldo Cruz Institute, Rio de Janeiro, found aviptadil blocked replication of the virus in human lung cells in laboratory conditions. 

The same experts, writing their findings in a pre-print paper, also said survivors who were hooked up to ventilators had more VIP in their blood than those who died of respiratory failure.  

Speaking of the findings so far, NeuroRx CEO Jonathan Javitt said: ‘No other antiviral agent has demonstrated rapid recovery from viral infection and demonstrated laboratory inhibition of viral replication.’ 

VIP has been shown to have anti-inflammatory properties in animals. Inflammation is a known complication of Covid-19 with fatal consequences.

VIP prevents production of inflammatory cytokines — which in high levels can cause lung injury.

Cytokines are a proteins in the body that give signals between cells. They play an important role in normal immune responses.

When the body releases too many inflammatory-provoking cytokines in one go, it’s called a ‘cytokine storm’.

It is thought to be a major factor behind lung damage, catastrophic organ failure and death in some coronavirus patients. 

Just two medicines — remdesivir and dexamethasone — have been shown to reduce the risk of death in patients already hospitalised.

Dexamethasone could save up to 35 per cent of Covid-19 patients relying on ventilators – the most dangerously ill – and reduce the odds of death by a fifth for all patients needing oxygen at any point, researchers led by Oxford University showed.

Remdesivir — an experimental drug originally designed to treat Ebola — has already been approved to treat Covid-19 patients in the UK since May. 

But the study results for Remdesivir are not as conclusive as dexamethasone.

Gilead Sciences Inc, who manufacturers the drug, found it reduced the risk of death in severely ill coronavirus patients by 62 per cent. But the study was retrospective, and not a random placebo controlled trial.

WHAT DRUGS ARE IN THE PIPELINE TO TREAT COVID-19?

Remdesivir 

Remdesivir was developed by Gilead Sciences to treat Ebola, the deadly hemorrhagic fever that emerged in West Africa in 2014. Trials produced encouraging results earlier this year when it showed promise for both preventing and treating MERS – another coronavirus – in macaque monkeys. Studies on humans have produced mixed results.

Health Secretary Matt Hancock dubbed remdesivir the ‘biggest step forward’ in treating Covid-19 since the outbreak spiralled out of control. Britain currently gets its supplies of remdesivir for free because of a Gilead deal to donate 1.5million vials across the world. 

SNG001 

SNG001 uses a protein called interferon beta which the body produces when it fights a viral infection. It has been developed by Southampton-based pharmaceutical firm Synairgen and trialled by researchers from the city’s university.

The treatment sees patients inhale the drug directly into the lungs using a nebuliser, where it helps the immune system fight off viral infection.

Initial results from the trial of more than 100 hospitalised Covid-19 patients found it prevented 79 per cent of them from needing intensive care, suggesting it stops the disease in its tracks.

Steroids 

Patients treated with steroids have shown to have better outcomes than those who are not. NHS officials approved dexamethasone for use on critically-ill patients after results of the world’s biggest Covid-19 drug trial found it could cut their risk of death. The steroid prevents the release of substances in the body that cause inflammation, a nasty Covid-19 complication that makes breathing difficult. In seriously unwell patients, the lungs become so inflamed they struggle to work. 

Bemcentinib 

This tablet developed by the Norwegian company BerGenBio is known as an AXL kinase inhibitor. In lab tests have shown it has potent anti-viral activity against several enveloped viruses, including Ebola and Zika virus. Preliminary data suggest bemcentinib is potentially useful for the treatment of early SARS-CoV-2 infection.

MEDI3506

MEDI3506 is made by MedImmune, a subsidiary of drug giant AstraZeneca. The anti-inflammatory injection is an interleukin-33 inhibitor. An IL-33 inhibitor such as Medi3506 acts to dampen down the cytokine storm as a result of the immune system going into overdrive in response to an infection.

Acalabrutinib  

Calquence, generic name acalabrutinib, is produced by British company AstraZeneca. It blocks the BTK protein which triggers an immune response – which can go haywire following an infection. Calquence was given to a small number of COVID-19 patients at the Walter Reed General Hospital in Washington. Experts observed it had ‘some clinical benefit’.

AstraZeneca, headquartered in Cambridge, said ‘clinical benefit was observed in select patients with advanced lung disease’. 

Zilucoplan 

This drug injected under the skin is developed by the Belgian company UCB. The treatment was developed originally by Ra Pharmaceuticals. Zilucoplan is a synthetic molecule designed to bind and inhibit portions of the immune system called the complement system. By blocking the complement system, zilucoplan may be able to reduce the attack of healthy tissues in the lung, preventing worsening of Covid-19.

Heparin 

Heparin is a blood thinner and is sold in many different products, marketed as Fragmin, Monoject Prefill Advanced and Innohep. Blood clotting problems have emerged in severe and critically-ill Covid-19 patients, affecting the lungs, heart and brain. Some patients are dying from heart attacks or strokes, a complication of the virus.

Tocilizumab 

This arthritis drug, marketed as RoActemra, was hoped to stop the ‘cytokine storm’ — an overreaction of the immune system causing inflammation — seen in some coronavirus patients. Tocilizumab reduces levels of IL-6, a cytokine that promotes inflammation in the body found in high levels in patients with autoimmune conditions. It’s in a number of clinical trials but results have been varied.

Favipiravir 

Favipiravir is a Japanese flu drug that blocks the ability of a virus to replicate itself, favipiravir has been shown to cut recovery time from 11 days to four days in coronavirus patients. Russian officials modified a version of the generic drug favipiravir to make it specifically for Covid-19. Covid-19 patients given the drug recovered in half the time compared to those who took a placebo and that it cures 90 per cent of patients in 10 days, health chiefs in Russia claimed.

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