Roche says a second trial of Actemra revives hopes for IL-6. What now?
Roche’s Actemra — and the IL-6 drug class by extension — may have a role in the fight against Covid-19 after all.
Data from a new Phase III study showed that adding the drug to standard of care could reduce hospitalized patients’ likelihood of needing mechanism ventilation, the Swiss pharma giant reported. Importantly, the majority of the 389 enrolled patients are from minority racial and ethnic groups who are often underrepresented in clinical trials but bear the brunt of the pandemic.
On the primary endpoint, patients with Covid-associated pneumonia who took Actemra were 44% less likely to need mechanism ventilation or die down the road, compared to the placebo arm (p-value = 0.0348). The proportions of patients who did within 28 days were 12.2% and 19.3%, respectively.
Dubbed EMPACTA, the trial used a different outcome measure from that used in the COVACTA study, which also involved patients with pneumonia but appeared to have recruited a more severe group, and focused on improvement in clinical status. Actemra failed to differentiate itself from placebo there, spelling what many assumed was an end to the idea of repurposing the rheumatoid arthritis drug to fight the uncontrolled immune response and lung damage that can result from Covid-19.
Back in July, Roche investigators did highlight one bright spot — a modest 0.037 p value for cutting the time to discharge — which didn’t count for much with the primary endpoint flop.
But that data point wasn’t held up in the new numbers released this morning, as the difference in time to hospital discharge or “ready for discharge” at day 28 was not statistically significant. Median days to discharge were 6 for Actemra and 7.5 for placebo, with a p-value of 0.2456.
All the other secondary endpoints also failed to hit statistical significance, including mortality and time to clinical failure.
It’s unclear how these results would stack up in the eyes of regulators as Roche brings the data to the FDA and other agencies around the world. Levi Garraway, head of global product development, said that reducing the need for mechanism ventilation is “an important outcome.”
In separate studies, Regeneron and Sanofi have concluded early on that Kevzara — which works similarly to Actemra, blocking the cytokine IL-6 — was likely having little effect on most but the most critical patients (who are already on ventilators at enrollment). The drug later failed all primary and secondary endpoints even in that subgroup, and the partners announced they were essentially pulling a plug on the program.
Roche is apparently not ready to give in. There’s one more Phase III study underway testing a combination of Actemra and remdesivir, Gilead’s EUA-blessed antiviral. Clinical status will be the primary endpoint for the REMDACTA trial, which targets severe patients with pneumonia; secondary endpoints include mechanical ventilation, mortality and intensive care variables.
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