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Five new drugs to be trialled on NHS Covid-19 patients 

A blood thinning drug and experimental cancer treatment pill are among five drugs which will be trialled on Covid-19 patients in NHS hospitals.

The medications are part of the first wave to be selected from a list of 200 potential candidates, and will each be tested on dozens of hospitalised patients.

If proven to be effective, officials will fast-track them into larger coronavirus trials in the UK involving thousands of Brits infected with coronavirus. 

One of the drugs is heparin, a blood-thinner used to treat heart attacks and hoped to stop blood-clotting observed in critically-ill Covid-19 patients. 

Scientists also hope zilucoplan, produced by Belgian firm UCB, will reduce damage to healthy lung tissue caused by the virus.

The Department of Health had already revealed compounds bemcetinib, MEDI3506 and acalabrutinib were involved in the trial.

A total of six drugs will initially enter the programme – but the sixth drug has not yet been revealed.

British-Norwegian biopharma company BerGenBio's bemcentinib was the first drug to be selected to go into phase 2 studies

British-Norwegian biopharma company BerGenBio's bemcentinib was the first drug to be selected to go into phase 2 studies

British-Norwegian biopharma company BerGenBio’s bemcentinib was the first drug to be selected to go into phase 2 studies 

Heparin, a blood-thinning agent used on the NHS in products such as Fragmin, will be given to Covid-19 patients for the first time next month

Heparin, a blood-thinning agent used on the NHS in products such as Fragmin, will be given to Covid-19 patients for the first time next month

Heparin, a blood-thinning agent used on the NHS in products such as Fragmin, will be given to Covid-19 patients for the first time next month

Thirty NHS hospitals across Britain will be involved in the ACCORD study, which was approved to begin at the end of April.

The University of Southampton-led trial aims to give an early indication of whether a drug is effective in treating hospitalised coronavirus patients. 

Once proven successful, the drugs can enter larger clinical trials such as RECOVERY – currently the world’s largest randomised trial run by Oxford scientists.

Calquence is a medication for a type of non-Hodgkin lymphoma known as mantle cell lymphoma but has the potential to dampen the body's aggressive immune response to Covid-19

Calquence is a medication for a type of non-Hodgkin lymphoma known as mantle cell lymphoma but has the potential to dampen the body's aggressive immune response to Covid-19

Calquence is a medication for a type of non-Hodgkin lymphoma known as mantle cell lymphoma but has the potential to dampen the body’s aggressive immune response to Covid-19

‘We are looking for a signal of both safety and efficacy, something that could reduce the severity of the disease, shorten its duration and prevent patients going into the intensive care environment,’ Tom Wilkinson, ACCORD’s academic lead told The Guardian.

The respiratory medicine professor and consultant, from the NIHR Southampton Biomedical Research Centre, said: ‘These are small, rapidly deliverable studies if we get patients in so we’re looking only to achieve around 60 patients for each arm of the trial to receive one of the drugs compared to usual standard of care.’

NHS hospitals that have signed up include St Thomas’ and Guy’s in London – where Boris Johnson was treated – and major hospitals in Liverpool, Manchester, Leeds, Leicester and Glasgow. 

British-Norwegian biopharma company BerGenBio’s Bemcentinib was the first drug to be selected to go into the phase two study – the stage of a clinical trial focused on the testing of a drug on patients to assess how effective it is and side effects.

The once-a-day pill, originally developed for cancer, is hoped to defend against coronavirus by stopping it from entering cells and preventing it ‘switching off’ one of the body’s most important antiviral defence mechanisms. 

BerGenBio chief executive Richard Godfrey told The Mail on Sunday that he was ‘extremely optimistic’ the pill would save lives. ‘I think there’s an 80 per cent probability of it working and being of benefit to patients,’ he said. 

The results of a trial of 120 patients at Southampton General Hospital are expected at the end of June.

Laboratory studies by the University of Iowa found the pill could boost immune response and switch off AXL receptors, which when turned on, allow the virus to enter and multiply in lung cells. 

The Department of Health revealed one of the others being looked at is acalabrutinib, the generic name for Calquence, produced by AstraZeneca. 

WHAT OTHER DRUGS ARE BEING TESTED? 

Only limited numbers of people can be enrolled in trials and only certain people – usually otherwise healthy patients – are eligible for them. 

For those who do make it onto trials there is often still a 50/50 chance that they get a placebo – a fake drug – anyway. 

These are some of the medicines being trialled on COVID-19 patients in the UK:

  • Lopinavir-Ritonavir (normally used to treat HIV) 
  • Dexamethasone (a steroid)
  • Azithromycin (pneumonia; Lyme disease; chlamydia)
  • Tocilizumab (rheumatoid arthritis) 
  • Hydroxychloroquine (malaria prevention; lupus; rheumatoid arthritis)
  • Convalescent plasma (blood from a recovered patient)
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Calquence is a medication for a type of non-Hodgkin lymphoma known as mantle cell lymphoma but has the potential to dampen the body’s aggressive immune response to Covid-19.

A small study of the drug at the Walter Reed General Hospital in Washington showed ‘some clinical benefit’ against Covid-19.

Jose Baselga, of AstraZeneca, the company which will produce billions of doses of Oxford University’s experimental vaccine, told Forbes the effects of Calquence ‘are clear’.   

Officials have revealed MEDI3506, also produced by MedImmune, a subsidiary of Cambridge-based AstraZeneca, will be involved in the ACCORD trial. 

It has been dished out in early trials for eczema and chronic obstructive pulmonary disease (COPD) – a crippling lung condition. 

It works by dampening down an over-reaction of the immune system, which can be prompted by the body reacting to the coronavirus. 

Heparin, a blood-thinning agent used on the NHS, will be given to Covid-19 patients for the first time next month, The Guardian reported.

Dr Wilkinson claimed that it can have a ‘dramatic effect in the lung’ as the ‘big sticky molecules can attach to viruses and stop them from entering cells’.

The compound, used in drugs such as Fragmin to prevent blood clots, may also be useful for critically ill Covid-19 patients who are at risk of blockages.

Doctors say blood clots are responsible for a large amount of coronavirus deaths – even after a patient is discharged from hospital. 

Other studies have shown abnormal blood-clotting in Covid-19 patients results in a significantly increased risk of heart attacks and strokes. 

Experts hope a fifth drug, called zilucoplan, will stop the overreaction of the immune system, which can lead to the death of healthy lung tissue.

‘A lot of the damage is focused on the blood cells and the very small blood vessels in the lung,’ Dr Wilkinson said. 

UCB’s drug – originally given to treat a skeleto-muscular disorder called myasthenia gravis – is injected under the skin. 

MailOnline has contacted the Department of Health and Social Care for details of the sixth drug that is being tested.  

British scientists are hoping hundreds of patients will sing up for trials of medicines which will speed up the race for a cure.

It comes just days after global studies – including Britain’s landmark RECOVERY trial – of hydroxychloroquine were halted.

Concerns about the Donald Trump-touted medicine were raised in a scientific paper published in The Lancet, that found it raised the risk of death and had no benefit.  

RECOVERY also looks at antibiotic azithromycin, steroid dexamethasone, HIV drug lopinavir-ritonavir, and an anti-inflammatory called tocilizumab.

WHAT ARE THE FIVE DRUGS? 

Bemcentinib

Who makes it?

It’s a tablet developed by the Norwegian company BerGenBio. It’s known as an AXL kinase inhibitor.

What have studies shown?

Bemcentinib is likely to have been chosen because 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.

How does it work? 

Lab studies by the University of Iowa found the pill can boost immune response and switch off AXL receptors, which when turned on, allow the virus to enter and multiply in lung cells. 

The number of AXL receptors increases when their environment is stressed, particularly when viruses start multiplying in the body. When AXL receptors are hijacked by invading viruses, the cell’s antiviral powers are switched off and it becomes defenceless to the disease.

Blocking AXL receptors also prompts a type I interferon response, alerting the body to the coronavirus and calls for more immune cells to attack it. 

What does it usually treat?

Bemcentinib was being trialled against cancers, including adult acute myeloid leukemia and non-small cell lung cancer (NSCLC). But it is not approved as a treatment in any country. 

MEDI3506

Who makes it?

MedImmune, a subsidiary of drug giant AstraZeneca. The anti-inflammatory injection is an interleukin-33 inhibitor.

What have studies shown?

No results from Covid-19 patients have been released yet.

How does it work?

Interleukin-33 (IL-33) is a cytokine involved activating the immune system. It acts as an alarm signal to alert various types of immune cells to trauma.

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.

What does it usually treat?

It’s being tested for chronic obstructive pulmonary disease (COPD), dermatitis, and diabetic kidney disease.

Acalabrutinib

Who makes it?

Calquence, generic name acalabrutinib, is produced by British company AstraZeneca. It is a Bruton’s tyrosine kinase (BTK) inhibitor.

What have studies shown?

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’.

How does it work?

COVID-19 can kill when it sparks an aggressive immune response that scars the lungs, making it difficult to breathe.

BTK inhibitors blocks the BTK protein which triggers immune responses. The immune response can go haywire following infection which leads to a so-called cytokine storm. A cytokine storm eventually begins damaging the body itself and, if left unchecked, can be fatal.

By suppressing the exaggerated defence mechanism, it may prevent the virus from damaging the lungs.

Jose Baselga, head of oncology research and development at AstraZeneca, told Forbes: ‘The science of acalabrutinib and, I think more than that, of Bruton’s tyrosine kinase situation, is pretty strong. The mechanism is very clear.’

What does it treat?

It’s a medication used to treat a type of non-Hodgkin lymphoma known as mantle cell lymphoma. It works by blocking BTK that contributes to cancer cell growth and survival.

Zilucoplan

Who makes it?

A drug injected under the skin developed by the Belgian company UCB. The treatment was developed originally by Ra Pharmaceuticals.

What have studies shown?

Nothing has been released for Covid-19 so far.

How does it work?

Zilucoplan is a synthetic molecule designed to bind and inhibit portions of the immune system called the complement system. The complement system is made up of a large group of blood proteins that are involved with the immune system but can kill cells and lead to catastrophic lung and tissue damage.

‘A lot of the damage is focused on the blood cells and the very small blood vessels in the lung,’ Dr Wilkinson said. 

By blocking the complement system, zilucoplan may be able to reduce the attack of healthy tissues in the lung, preventing worsening of Covid-19.

What has it been used for?

It has shown to improve myasthenia gravis, a skeleto-muscular disorder, in ongoing clinical trials.

Heparin

Who makes it?

Heparin is an ingredient sold in many different products, marketed as Fragmin, Monoject Prefill Advanced and Innohep.

What have studies shown?

No results have been published yet. It will be given to Covid-19 patients for the first time next month.

How does it work?

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.

It’s left doctors considering whether blood thinners should be given to certain patients during their stay and afterwards.

In a number of conditions, heparin has been shown to ‘have a dramatic effect in the lung’ when taken with a nebuliser, said Wilkinson. ‘It is a big sticky molecule which can attach to viruses and stop them from entering cells and secondly it may have an important anti-inflammatory effect,’ he said.

What has it been used for?

Heparin is a blood thinner used to treat and prevent blood clots caused by certain medical conditions. It is also used before surgery to reduce the risk of blood clots.

It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.

Source: Daily Mail | Top Health News

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