COVID-19: Keep up to date with the latest pharmaceutical and healthcare news as the pandemic evolves

 

PharmaTimes talks to...Professor Saad Shakir

4th June 2020

Professor Shakir, director of the Drug Safety Research Unit, explains the cytokine storm, a major killer in patients with severe COVID-19 infection

Professor Shakir, director of the Drug Safety Research Unit, explains the cytokine storm, a major killer in patients with severe COVID-19 infection

What are cytokines?

Cytokines are a group of proteins that are secreted by cells in the immune system.

They act as chemical messengers to regulate other immune cells, exerting their effects in tissues locally or further afield by circulating in the blood and lymph.

Essentially, cytokines are released from one immune cell to affect the actions of another cell in the immune system by binding to receptors on its surface. They include interferons, interleukins, lymphokines and tumour necrosis factors.

Cells which release cytokines include macrophages, lymphocytes (both B and T lymphocytes) and other immune cells.

Cytokines exert their functions by allowing immune cells to communicate; they can activate or inhibit immune cells, control their development or direct immune cell movement.

In systemic viral infections, cytokines can induce an inflammatory response which is beneficial until their production becomes uncontrolled.

What is a cytokine storm?

This is the condition which happens in viral infections where a huge amount of cytokines are produced. It can make the patients far sicker by causing multi-organ failure, which is frequently fatal.

Simply put, a cytokine storm or surge is an uncontrollable flood of cytokines which tends to worsen respiratory function and produce multi-organ failure. Cardinal features of a cytokine storm include unremitting fever, cytopenia, massive increase in ferritin, high ESR (erythrocyte sedimentation rate) and Adult Respiratory Distress Syndrome (ARDS).

In COVID-19 this cytokine storm is associated with increased levels of interleukins IL2-2, IL-7 and other cytokines. A mortality predictor in a cytokine storm is the level of ferritin, while thrombocytopenia is also a marker of a fatal outcome.

Cytokine storms can be more severe in young patients who have more efficient immune systems and responses than older patients. Usually it occurs a few days after the onset of the illness and was the major killer with the Asian Influenza in 1959.

What is the current treatment approach?

Treatment is supportive including management of ARDS.

According to a Lancet paper: 'As during previous pandemics (Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome), corticosteroids are not routinely recommended and might exacerbate COVID-19-associated lung injury'. However, in hyperinflammation, immunosuppression is likely to be beneficial. Re-analysis of data from a Phase III randomised controlled trial of IL-1 blockade (anakinra) in sepsis showed significant survival benefit in patients with hyperinflammation, without increased adverse events. A multicentre, randomised controlled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19 pneumonia and elevated IL-6 in China (ChiCTR2000029765). Janus kinase (JAK) inhibition could affect both inflammation and cellular viral entry in COVID-19.'

Other suggested therapies are tacrolimus and mycophenolate, both of which are immunosuppressants inhibiting IL-2 and other cytokines, which are used in patients with solid organ transplants. However, there are no double blind randomised clinical trials that assessed their benefit in this indication.

Professor Shakir is director of the Drug Safety Research Unit

 

Hydroxychloroquine fails as postexposure prophylaxis for COVID-19

4th June 2020

However, the trial did have limitations, researchers note

As of this morning – Wednesday June 3 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 279,856 with 39,728 deaths.

Researchers have found that giving hydroxychloroquine as postexposure prophylaxis for COVID-19 did not prevent illness.

The study, published in the New England Journal of Medicine, enrolled adults who had exposure to someone with confirmed COVID-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure).

Within four days of exposure, participants were randomly assigned to receive either placebo or hydroxychloroquine (800mg once, followed by 600mg in six to eight hours, then 600mg daily for four additional days).

The incidence of new illness compatible with COVID-19 was not significantly different between those receiving hydroxychloroquine (11.8%) and those receiving placebo (14.3%). Also, the researchers noted that side effects were more common with hydroxychloroquine (40.1% versus 16.8% for placebo), but that no serious reactions were observed.

However, Boulware et al. did note that their trial had limitations, because the vast majority of participants were unable to access testing in the US, so it was difficult to determine how many actually had COVID-19.

'Whether preexposure prophylaxis would be effective in high-risk populations is a separate question, with trials ongoing,' they also stressed.

 

Gov't launches public info campaign for track and trace

3rd June 2020

It will reiterate the need for those who have been close to someone testing positive for coronavirus to self-isolate

As of this morning – Wednesday June 3 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 277,985 with 39,369 deaths.

Health and Social Care Secretary Matt Hancock has launched a new government public information campaign for the new NHS Test and Trace service.

The campaign includes a new animated TV advert, voiced by actor Mark Strong, as well as radio, print, online, and out-of-home content setting out important public health information

It will reiterate the need for self-isolation and testing as soon as symptoms develop, in bid to rein in the spread of the virus.

Anyone who tests positive for coronavirus will now be contacted by NHS Test and Trace and asked to share information about their recent interactions.

People identified as having been in close contact with someone who has a positive test must then also self-isolate at home for 14 days, even if they do not have symptoms.

“NHS Test and Trace will not succeed on its own – we all need to play our part, Dido Harding, executive chair of NHS Test and Trace, said then the service was launched last week.

“This is why we are working hand-in-hand with communities and local authorities across the country to tailor support at a local level, and respond quickly to local needs.

“Together we can help contain the virus, stop it spreading further and ultimately save lives”.

 

First patient dosed in bemcentinib COVID-19 trial

3rd June 2020

Bemcentinib was selected as the first candidate to be tested as part of the UK ACcelerating COVID-19 Research & Development platform (ACCORD) study

As of this morning – Wednesday June 3 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 277,985 with 39,369 deaths.

Dosing has commenced in the UK Government-backed Phase II clinical trial assessing BerGenBio's bemcentinib in hospitalised COVID-19 patients.

Bemcentinib was selected as the first candidate to be tested as part of the ACcelerating COVID-19 Research & Development platform (ACCORD) study, launched by the Department of Health and Social Care and UK Research and Innovation (UKRI) at the end of April.

ACCORD essentially brings together a single, UK-wide clinical trial platform to rapidly test potential drugs through early stage clinical trials and feed them into the UK's large-scale COVID-19 studies.

The first patient has been dosed with bemcentinib at the University Hospital Southampton NHS Foundation Trust. The Phase II study, which is open in a further seven sites across the UK, will recruit 120 subjects in total, assessing the safety and efficacy of bemcentinib as an add on therapy to standard of care (SoC) in 60 hospitalised COVID-19 patients with a further 60 control group patients receiving SoC.

BerGenBio anticipates that top line data will readout later in the summer. If positive, the drug will then be advanced into large-scale Phase III trials in the UK.

The study is fully funded by the DHSC and UKRI and is being managed by clinical research company IQVIA. Drug material and other trial resources will be provided by BerGenBio.

“Initiating this clinical trial in such short order is the result of tremendous teamwork between my colleagues at BerGenBio and the teams at IQVIA and UHS, among many others,” said Richard Godfrey, the firm's chief executive. “This illustrates exactly what can be achieved when we all work together and focus on delivering the best experimental drug candidates to patients that so urgently need them.”

 

PIONEER COVID-19 trial wins funding injection from LifeArc

2nd June 2020

The funds will enable researchers to investigate the science around the trial, including why coronavirus affects some people more than others

As of this morning – Tuesday June 2 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 276,332 with 39,045 deaths.

The PIONEER clinical trial, which is testing treatments for COVID-19, has received a funding injection of nearly £1.37 million from medical research charity LifeArc.

The randomised trial at Chelsea and Westminster Hospital and West Middlesex University Hospital is assessing the potential or repurposing existing medicines for the treatment of patients with mild to moderate COVID-19.

The randomised study is comprised of three arms: the Japanese antiviral drug favipiravir, a combination of hydroxychloroquine, azithromycin and zinc and standard of care.

Following a competitive pitch by 130 organisations globally, Chelsea and Westminster Hospital NHS Foundation Trust, together with Imperial College, were among the 15 chosen to receive funding from a pot of £10 million.

Chief investigator of PIONEER Prof Pallav Shah is to receive the funding, which has been earmarked for scientific research to investigate the effects of the trial drugs on patients.

“The LifeArc grant makes it possible to conduct this trial looking at the treatment strategy using the novel Japanese antiviral drug favipiravir, and also to study in a more robust manner the effects of hydroxychloroquine, azithromycin and zinc, in these patients with Coronavirus infections,” said Prof Pallav Shah, PIONEER principal investigator and recipient of the grant.

“It (the grant) also gives us an amazing opportunity to try and evaluate the effects of the virus on patients, and also related to the patients’ profile, than would have been possible previously (without the grant). We can use very modern techniques, such as single-cell sequencing, to try and understand the response to treatment, and the best way of treating the infection.”

Around £750,000 will be allocated to researching the science around the trial at the Chelsea and Westminster Hospital NHS Foundation Trust, with the remaining £620,000 to be injected into research at Imperial College.

 

Coronavirus bottleneck leaves 2m waiting for cancer care

2nd June 2020

2.1 million people are waiting for breast, bowel or cervical screening

As of this morning – Tuesday June 2 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 276,332 with 39,045 deaths.

Around 2.4 million people in the UK are currently waiting for cancer screening, tests or cancer treatment, a new analysis by Cancer Research UK has found.

The charity says COVID-19 has caused 'enormous disruption' to cancer services throughout the UK, with delays to cancer treatment, screening and diagnosis, and 'huge decreases' in urgent referrals to hospital of patients with suspected cancer symptoms.

The charity has found a backlog of around 2.1 million people left waiting for breast, bowel or cervical screening, and notes that during this time, 3,800 cancers would normally be diagnosed through screening.

Urgent cancer referrals have been 'severely impacted' with up to 290,000 people missing out on further testing, which would detect up to 20,300 cancers in the same time period, it warns, also highlighting a backlog of treatment to catch up on, with up to 12,750 fewer patients receiving surgery, 6,000 fewer for chemotherapy and 2,800 fewer receiving radiotherapy since lockdown began.

The charity says ‘COVID-protected’ safe spaces will be a crucial part of tackling this backlog and ensuring more people can safely receive treatment or be diagnosed quickly, but stresses that this will only be feasible if all cancer patients and healthcare staff – whether symptomatic or asymptomatic – are tested regularly for the virus.

It also calls for a 'clear national plan' for testing to facilitate the recovery and restoration of cancer services across the country.

“The enormous strain COVID-19 has placed on cancer services is of great concern to us,” said Michelle Mitchell, Cancer Research UK’s chief executive.

“To get cancer services back to normal levels while ensuring no one is put at risk, frequent testing of NHS staff and patients, including those without symptoms, is vital. We now need clear national leadership and guidance for the NHS to dramatically increase testing levels. At the moment, we don’t know who is responsible for making cancer services safe and it’s patients who are suffering in the meantime. The Government must work closely with the NHS to ramp up testing provision with rapid results, as quickly as possible once practical.

“Prompt diagnosis and treatment remain crucial to give people with cancer the greatest chances of survival and prevent the pandemic taking even more lives.”

 

CRUK, Latus and Edinburgh Uni launch test camostat for COVID-19

29th May 2020

The treatment for pancreatic inflammation has been shown in the lab to prevent COVID-19 from entering human cells

As of this morning – Friday May 20 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 269,127 with 37,837 deaths.

Cancer Research UK and its partners have kicked off a clinical trial to determine the potential of repurposing a drug used to treat inflammation of the pancreas for the treatment of COVID-19.

The SPIKE1 trial, funded by LifeArc and a partnership between the charity's Centre for Drug Development (CDD), Latus Therapeutics and the University of Edinburgh, will investigate whether camostat, which has been shown in the lab to prevent COVID-19 from entering human cells, could help control symptoms of the virus and prevent hospitalisation.

The drug is already licensed for use in Japan and South Korea to treat pancreatic disease, so if successful it could be quickly manufactured and used to treat people with COVID-19, the charity notes. The fact that it is already approved also allowed camostat to proceed straight to a Phase III clinical trial in this setting.

The trial will take place in the community, recruiting people with symptoms of COVID-19 before they require hospital care. Those receiving treatment will take daily doses of the tablet and all patients will be assessed daily by telephone and self-report their temperature and blood oxygen levels.

Almost half of UK COVID-19 patients requiring critical care have died in hospital so far, highlighting the critical need for new treatment options alongside the development of a successful vaccine. Researchers believe that repurposing already available drugs such as remdesivir or camostat to treat COVID-19 could save lives.

“We believe [camostat] could be used to reduce the severity of COVID-19 infection, providing much needed time for the body’s immune system to recognise the virus and destroy it. Unlike finding a vaccine, this drug could be used quickly to help people recover from COVID-19,” said Dr Bobojon Nazarov, founder of Latus.

“We’re seeing the impact of COVID-19 on cancer patients throughout the country and we have the skills at Cancer Research UK to assist the national effort in helping to beat this virus, and support from LifeArc is critical to this new trial,” noted Iain Foulkes, executive director of research and innovation at Cancer Research UK.

“The charity’s Centre for Drug Development has a strong track record in setting up trials quickly, which is a testament to our sector leading ways of working. The team have shown that in these uncertain times they’ve not only managed to continue treatment for all cancer patients on their Phase I trials, but also excelled at this challenge and lent their expertise to others in need. Because we know that the sooner we can find ways to minimise the impact of COVID-19, the more quickly we can more fully return to our life saving cancer research.”

 

PureTech advances experimental COVID-19 drug into global trials

28th May 2020

LYT-100 employs a multimodal mechanism of action to potentially reduce, delay or prevent the lung dysfunction documented in COVID-19 patients

As of this morning – Thursday May 28 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 267,240 with 37,460 deaths.

UK clinical-stage biotherapeutics group PureTech has unveiled plans to advance its wholly-owned clinical-stage product candidate LYT-100 (deupirfenidone) as a potential treatment for serious respiratory complications, including inflammation and fibrosis, that persist following the resolution of SARS-CoV-2 (COVID-19) infection.

The firm says LYT-100 employs a multimodal mechanism of action to potentially reduce, delay or prevent the lung dysfunction documented in COVID-19 patients, including those who have recovered from the infection.

The global, randomised, placebo-controlled trial is expected to begin in the third quarter and will evaluate LYT-100 in non-critical COVID-19 patients with respiratory complications, with top-line data expected mid 2021.

“Hundreds of clinical trials are underway to combat COVID-19, but the vast majority are focused on vaccines or the acute treatment of severe patients,” said Dennis Ausiello, former chief of medicine at Massachusetts General Hospital and a member of the PureTech R&D Committee.

“As we learn more about the full impact of COVID-19 on the body, we’re seeing post-recovery, longer-term pulmonary dysfunction similar to that observed following infection with other coronaviruses, including SARS and MERS.

“In fact, emerging data suggest that a high proportion of COVID-19 patients are at risk of impaired lung function and fibrosis after recovery, as well as during acute infection. With more than five million documented infections to date worldwide, there is a clear and urgent need for therapeutics to address the longer-term sequalae of COVID-19.”

LYT-100 is an oral anti-fibrotic and anti-inflammatory small molecule. It is a deuterated analogue of pirfenidone, a drug approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the US, EU, Japan and a number of other countries.

In prior Phase I, healthy volunteer studies, 'LYT-100 has shown a differentiated and superior pharmacokinetic profile compared to pirfenidone, suggesting improved efficacy, tolerability and safety, while retaining the same intrinsic pharmacology of pirfenidone. Preclinical research also shows that LYT-100 potently inhibits a range of pro-inflammatory cytokines including IL6, TNF alpha and TGF-beta,' PureTech noted.

 

Government launches coronavirus test and trace service

28th May 2020

Anyone who tests positive for coronavirus will be contacted by NHS Test and Trace and will need to share information about their recent interactions

The UK government has today launched its NHS Test and Trace service in a bid to identify, contain and control coronavirus to reduce its spread and save lives.

From now, anyone who tests positive for coronavirus will be contacted by NHS Test and Trace and will need to share information about their recent interactions, including people they have been in direct contact with.

People identified as having been in close contact with someone who has a positive test must stay at home for 14 days, even if they do not have symptoms, to stop unknowingly spreading the virus.  But members of their own household will not have to stay at home unless the person identified becomes symptomatic, at which point they would also self-isolate for 14 days.

"As we move to the next stage of our fight against coronavirus, we will be able to replace national lockdowns with individual isolation and, if necessary, local action where there are outbreaks,” said health secretary Matt Hancock.

"NHS Test and Trace will be vital to stopping the spread of the virus. It is how we will be able to protect our friends and family from infection, and protect our NHS.”

NHS Test and Trace brings together four tools to control the virus:

  • Test: increasing availability and speed of testing
  • Trace: when someone tests positive for coronavirus the NHS Test and Trace service will use dedicated contact tracing staff, online services and local public health experts to identify any close recent contacts they’ve had and alert those most at risk. This will be complemented by the rollout of the NHS Covid-19 App in the coming weeks.
  • Contain: A national Joint Biosecurity Centre will work with local authorities and public health teams in PHE to identify localised outbreaks and support effective local responses
  • Enable: Government to learn more about the virus, including as the science develops, to explore how we could go further in easing infection control measures.

“NHS Test and Trace will not succeed on its own – we all need to play our part. This is why we are working hand-in-hand with communities and local authorities across the country to tailor support at a local level, and respond quickly to local needs. And we will be constantly developing and improving as we go. Together we can help contain the virus, stop it spreading further and ultimately save lives,” said Dido Harding, executive chair of NHS Test and Trace.

“We welcome the clarity that has now been given on the test, track and trace strategy. We should not be in any doubt how crucial getting this right will be, and we are extremely glad to see the involvement of local leaders and experts,” commented Danny Mortimer, deputy chief executive of the NHS Confederation.

 

NHS patients to be given experimental coronavirus therapy remdesivir

27th May 2020

The drug will be provided to the NHS free of charge by Gilead via the UK's early access to medicines scheme

As of this morning – Wednesday May 27 – the current recorded case count for COVID-19 (coronavirus) in the UK has hit 265,227 with 37,048 deaths.

The government has announced that certain NHS patients with coronavirus will soon be able to access Gilead's remdesivir in a bid to speed up their recovery.

The drug is currently being tested in clinical trials around the world, with early data showing it can shorten the time to recovery by about four days.

The Early Access to Medicines Scheme (EAMS) and scientific opinion from the Medicines and Healthcare products Regulatory Agency (MHRA) supports NHS use of remdesivir where it is likely to deliver the greatest benefit.

Commenting on the move, Hilary Hutton-Squire, VP and general manager, Gilead Sciences UK and Ireland, said the firm is delighted that the MHRA and the Commission on Human Medicines (CHM) have issued remdesivir a positive Scientific Opinion within the EAMS.

“Treatment options in response to this global public health emergency are urgently needed and we are grateful to the UK government and the MHRA for their continued support and collaboration to make this medicine available to those patients who are most likely to benefit from it. We will continue to work closely with the government to supply remdesivir across the UK,” she added.

The MHRA's scientific opinion does not replace the normal licensing procedures for medicines but supports prescribers and patients to decide on whether to use the medicine before its licence is approved. As part of the scientific opinion, a framework to collect safety data and manage risks will be implemented, the agency noted.

Remdesivir’s current use in the UK will be for patients in cases of high unmet medical need through the EAMS, where it will be provided to the NHS free of charge by Gilead throughout the EAMS period. It will also continue to be used in clinical trials.

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