- An anti-inflammatory drug from Roche cut the risk of death in patients hospitalized with severe COVID-19, investigators in a massive British trial known as RECOVERY reported Thursday, a definitive finding that could change how patients with the disease are treated.
- Treatment with the drug, which Roche sells as Actemra, on top of standard care including the steroid dexamethasone was found to provide several benefits over typical treatment alone. For instance, patients who got Actemra were discharged from the hospital faster and were less likely to need mechanical ventilation. The benefits were seen across multiple subgroups, including those who were already on ventilators.
- The surprising outcome follows mixed results from multiple smaller studies of Actemra and other drugs like it — findings that left it possible but unclear whether they might help patients with advanced disease. Actemra is now just the second therapy, along with dexamethasone, to improve mortality in a large, randomized, placebo-controlled trial.
For nearly a year, researchers and drugmakers have run one study after another on Actemra and other so-called IL-6 inhibitors in patients severely ill with COVID-19. The goal has been to see if early, promising results from small, flawed studies in China and France, which found that Actemra seemed to keep those patients alive and off breathing support.
Those efforts had largely raised more questions than answers. First, Actemra failed in a 450-patient study called COVACTA. Then, Sanofi and Regeneron stopped researching their drug Kevzara in COVID-19 after reporting negative results.
But Roche and others kept studying IL-6 inhibitors, which has led to a more mixed picture. The Swiss drugmaker, reported in September that Actemra appeared to keep patients who had pneumonia associated with COVID-19 from needing intensive breathing support, though it didn't help them live longer. Then in January, U.K. researchers reported that both Actemra and Kevzara helped improve outcomes in COVID-19 patients in intensive care in a roughly 800-patient study called REMAP-CAP.
The results reported in the RECOVERY trial — a massive study testing a variety of antivirals, antibodies and other COVID-19 drugs — change the narrative altogether. RECOVERY has already shaped how COVID-19 patients are treated across the globe, having definitively proven the benefits of dexamethasone as well as the ineffectiveness of drugs like hydroxychloroquine and lopinavir/ritonavir.
Now, RECOVERY researchers have made clear that Actemra may have a role to play in treating COVID-19 as well. In the study, investigators randomized roughly 4,100 patients who needed oxygen and had evidence of inflammation. Some 2,022 patients received the Roche drug and standard of care, while another 2,094 were given just typical treatment. About four in five patients in the study received a systemic steroid such as dexamethasone.
RECOVERY researchers reported that 596, or 29%, of patients who got Actemra died within 28 days, versus 694, or 33%, in the control arm. That translates to an absolute difference of 4%, meaning one life would be saved for every 25 patients treated, they said in a statement.
Actemra patients were also more likely to be discharged from the hospital within that timeframe (54% versus 47%). Among those not yet on a ventilator, the drug reduced the chance of progressing to ventilation or dying (38% versus 33%), though benefits were seen across all groups of patients requiring some form of breathing support.
The data suggest dexamethasone and Actemra, which is also known as tocilizumab, reduce the risk of death by "about one third" in patients with "significant" inflammation and who need simple oxygen, and "nearly one half" in those on mechanical ventilation, according to the statement.
"The results from the RECOVERY trial clearly show the benefits of tocilizumab and dexamethasone in tackling the worst consequences of COVID-19 — improving survival, shortening hospital stay, and reducing the need for mechanical ventilators," said University of Oxford professor Martin Landray, one of the study's lead investigators, in the statement. "Used in combination, the impact is substantial."
The results will be published in a pre-print on medRxiv "shortly," the release said.