IL-6 drugs do work in COVID-19, says UK, as it plans NHS use

New data means that IL-6 drugs from Roche and Sanofi that had been all-but written off as coronavirus therapies will now be offered routinely to COVID-19  patients in intensive care in the UK.

The renaissance of the two therapies comes on the back of the REMAP-CAP trial, which found that the IL-6 inhibitors RoActemra (tocilizumab) and Kevzara (sarilumab) reduced the relative risk of death by 24% when administered to COVID-19 patients within 24 hours of entering intensive care, and reduce the time spent in hospital by seven to ten days.

Both RoActemra and Kevzara have failed to hit their objectives in earlier studies, leading to speculation that inhibiting IL-6 wasn’t a valid approach to treat severe COVID-19, but the new independent study turns that view on its head.

Crucially, their benefits seem to stack with that of the corticosteroid dexamethasone, the first drug to be shown to improve survival in seriously-ill COVID-19 patients in the RECOVERY trial.

The death rate for those in intensive care units on dexamethasone and respiratory support alone was 35%, but reduced to 28% when RoActemra was administered as well.

“The data shows that tocilizumab, and likely sarilumab, speed up and improve the odds of recovery in intensive care, which is crucial for helping to relieve pressure on intensive care and hospitals and saving lives,” said UK deputy chief medical officer Prof Jonathan Van-Tam.

The data has emerged as the government unveiled figures showing there are currently around 30,000 COVID-19 patients in hospitals, up nearly 40% on the previous peak during the first wave of the pandemic in April.

There are already ample supplies of RoActemra in the UK, so that drug in particular will be recommended for use “immediately” in patients admitted to intensive care with the virus, it said, saying that could potentially save “hundreds of lives”.

Roche welcomed the results, saying it was still in the process of analysing data from the COVACTA and EMPACTA trials, which generated negative and positive results for its drug respectively in patients hospitalised with COVID-19 associated pneumonia.

“Previous trials using IL-6 receptor agonists have showed no clear benefit on either disease progression or survival in COVID-19 patients, but those studies included less severely ill patients and started treatment at different stages in the disease course,” said Professor Anthony Gordon of Imperial College London, the trial’s lead investigator in the UK.

“A crucial difference may be that in our study, critically ill patients were enrolled within 24 hours of starting organ support. This highlights a potential early window for treatment where the sickest patients may gain the most benefit from immune modulation treatment,” he added.

REMAP-CAP has been running since 2016, with the aim of putting dozens of drugs through their paces to see if they can improve the prospects of people with severe community-acquired pneumonia (CAP) caused by influenza, but was expanded to include COVID-19 patients after the pandemic took hold.

It included more than 800 pneumonia patients in intensive care with suspected or proven COVID-19, of which around three-quarters were recruited from UK NHS trusts, but hasn’t yet been subjected to the scrutiny of peer review.

“This news is a positive step in the fight against COVID-19, giving doctors and the NHS another weapon in their armoury to treat critically ill patients,” said Marius Scholtz, chief medical officer at Roche Products Ltd. “It also increases the collective scientific understanding of COVID-19.”

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Setback in COVID-19 effort as Roche’s Actemra fails in key trial

Roche’s anti-inflammatory drug Actemra has failed in a phase 3 clinical trial that was testing to see if it improved the condition of patients with COVID-19 associated pneumonia.

The COVACTA trial of Actemra (tocilizumab) did not meet its primary endpoint of improved clinical status, or the secondary endpoint of reduced patient mortality.

The rationale behind the trial was that by inhibiting a chemical signal known as IL-6, Actemra would help to tackle the extreme immune reaction known as a cytokine storm in patients badly affected by COVID-19.

However the hypothesis looks somewhat shaky after Sanofi’s IL-6 Kevzara (sarilumab) also failed to produce results in a similar COVID-19 study.

Aside from being a setback in the effort against COVID-19, there are commercial implications too: sales of Actemra were better than expected during the first half of the year because of its use against the disease.

Actemra is already used to treat cytokine release syndrome (CRS) in patients who are undergoing CAR-T cancer therapy.

The Swiss pharma said it plans to continue with trials testing Actemra in other COVID-19 treatment settings, including in combination with an antiviral.

Although all four secondary endpoints were not met, there was a positive trend in time to hospital discharge in patients treated with the drug, which is also known as RoActemra in some regions.

The COVACTA study did not identify any new safety signals.

Roche said it will further analyse the full trial results, which will be submitted for publication in a peer-reviewed journal.

COVACTA was conducted in collaboration with the US government agency, the Biomedical Advanced Research and Development Authority (BARDA).

It tested safety and efficacy of intravenous Actemra added to standard-of-care treatment compared to treatment with placebo plus standard of care.

The primary endpoint of clinical status in hospitalised adult patients with severe COVID-19 associated pneumonia was measured by a scale that tracked patients’ clinical status based on the need for intensive care and/or ventilator use, as well as supplemental oxygen requirements.

Actemra is also being tested in the UK as a treatment for COVID-19, including in the RECOVERY trial, which includes several potential drugs and therapies.

Roche was in the unusual position of starting its trial after several smaller independent studies suggested Actemra could be used as a treatment for COVID-19.

Rav Seeruthun, Medical Director, Roche Products Limited said: “Whilst today’s news is incredibly disappointing, data from this trial will help scientists have a greater understanding of COVID-19.

“We should also celebrate the immense effort from so many groups to get to this point.

“There has been an unprecedented level of collaboration between industry, the NHS and others, in a way I’ve never seen before.  I hope it acts as a framework for future work beyond COVID-19.”

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