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.”