Another cytokine storm miss in Covid-19


Treating Covid-19-associated pneumonia with IL-6 inhibitors was looking dicey even before Sanofi’s Kevzara failed for the second time in this use. Now that the molecule that kickstarted the cytokine storm-based rationale, Roche’s Actemra, has disappointed in phase III the theory would seem kaput. The Covacta study in hospitalised patients with severe Covid-19-associated pneumonia failed to show a difference in clinical status between Actemra- and placebo-treated patients, via a seven-category ordinal scale, after four weeks’ treatment. Neither was there an effect on mortality at week four, with just under 20% of patients dying in each arm. The best Covacta could show was a non-significant trend favouring Actemra in the time to hospital discharge. Still, the IL-6 theory won’t die. Roche is pushing on with two more phase III Actemra trials, Remdacta and Empacta, in this indication. And investors are keeping faith with Tiziana, whose stock leapt 173% when it put its preclinical-stage IL-6 into Covid-19 trials: its shares are trading at a three-year high. If Tiziana’s MAb follows the others into clinical irrelevance Roche could lose out in another way, too – it is the only company to have an FDA-authorised test for IL-6 levels in Covid-19 patients.

Roche's phase III trials of Actemra in Covid-19
Trial N Details Primary endpoint Data
Covacta 450 Actemra vs placebo in hospitalised patients with severe Covid-19 pneumonia Clinical status via a seven-point ordinal scale Fail
Remdacta  450 Actemra plus remdesivir vs remdesivir plus placebo in hospitalized patients with severe Covid-19 pneumonia Clinical status via a seven-point ordinal scale Possible Q3 2020
Empacta 379 Actemra vs placebo in hospitalised patients with Covid-19 pneumonia, focusing on underserved and minority populations that often do not have access to clinical trials Proportion of participants needing mechanical ventilation by day 28 Possible Q3 2020
Source:; company communications. 

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