New findings released Thursday from the ongoing RECOVERY trial showed that Roche’s arthritis drug Actemra (tocilizumab) significantly reduced mortality among patients hospitalized with severe COVID-19, according to researchers leading the study at the University of Oxford. The intravenous IL-6 receptor monoclonal antibody also shortened the time to recovery and significantly cut the need for mechanical ventilation.
Peter Horby, joint chief investigator for RECOVERY, noted that “previous trials of [Actemra] had shown mixed results, and it was unclear which patients might benefit from the treatment. We now know that the benefits…extend to all COVID-19 patients with low oxygen levels and significant inflammation.” He added that the “double impact” of Actemra plus dexamethasone, another drug tested in RECOVERY that has been found to cut death rates by up to one-third in ventilated COVID-19 patients, “is impressive and very welcome.”
Absolute difference of 4% in mortality risk
RECOVERY is evaluating multiple potential treatments for people hospitalized with suspected or confirmed COVID-19 and has recruited over 36,100 participants globally so far. In the trial, a total of 2022 patients were randomly assigned to receive Actemra and were compared with 2094 patients randomised to usual care alone. Researchers noted that 82% of patients were taking a systemic steroid such as dexamethasone.
Preliminary findings showed that 29% of Actemra-treated subjects died within 28 days, compared with 33% of the usual-care group, translating to an absolute difference of 4%. Investigators said this was significant, noting that “for every 25 patients treated with [Actemra], one additional life would be saved.” Roche’s drug also increased the probability that patients would be discharged alive within 28 days, from 47% to 54%. “These benefits were seen in all subgroups, including those requiring oxygen via a simple face mask through to those requiring mechanical ventilators in an intensive care unit,” researchers said.
Benefits on top of those seen with steroids
Among patients who were not already intubated when they started the trial, treatment with Actemra significantly lowered the likelihood of them progressing to invasive mechanical ventilation or death, from 38% to 33%, although there was no evidence the IL-6 inhibitor improved their odds of getting off mechanical ventilation. Researchers said the benefits of Actemra “were clearly seen to be in addition to those of steroids,” such as dexamethasone, which is now part of the standard treatment regimen for severe COVID-19 patients since the survival benefit for that drug was reported last year.
According to the Oxford scientists, the new data suggest that in COVID-19 patients with hypoxia and significant inflammation, combining a systemic corticosteroid plus Actemra “reduces mortality by about one third for patients requiring simple oxygen, and nearly one half for those requiring invasive mechanical ventilation.” Preliminary results will be made available as a preprint via medRxiv shortly and also submitted for publication in a peer-reviewed journal.
Roche recently said Actemra posted sales of CHF 724 million ($814 million) in the fourth quarter of 2020, up 20% from the year-ago period. Bill Anderson, who heads the company’s drug division, recently suggested that previous mixed results for Actemra in COVID-19 were likely due to differences in the type of patients studied, when they were treated and the endpoint. “We think we’re sort of zooming in on both the most relevant endpoints and relevant patient population,” Anderson said, adding “it seems like the ideal candidates are patients who are really in that acute phase of inflammatory attack.”