Sanofi and Regeneron Pharmaceuticals Inc have said that they have stopped a late-stage trial on rheumatoid arthritis drug Kevzara for Covid-19, as it is not showing the desired outcome.

The “US Phase 3 trial of Kevzara® (sarilumab) 400 mg in Covid-19 patients requiring mechanical ventilation did not meet its primary and key secondary endpoints, when Kevzara was added to best supportive care compared to best supportive care alone (placebo),” a note from the companies said.

“Minor positive trends were observed in the primary pre-specified analysis group (critical patients on Kevzara 400 mg who were mechanically ventilated at baseline) that did not reach statistical significance and these were countered by negative trends in a subgroup of critical patients who were not mechanically ventilated at baseline,” the note added.

However, a separate Sanofi-led trial outside the US in hospitalised patients with severe and critical Covid-19, using a different dosing regimen, is ongoing, the companies said. The same Independent Data Monitoring Committee (IDMC) is overseeing both the Regeneron-led US trial and the Sanofi-led trial outside of the country which has recommended that the latter continue. The companies expect to report results in Q3, 2020.

Sanofi and Regeneron’s trial come as several companies and universities undertake studies to re-purpose existing drugs to tackle Covid. This, even as another 150-odd vaccine candidates undergo development studies to protect against Covid.

Kevzara is an injectable approved in many countries to treat adults with moderately to severely active rheumatoid arthritis who have not responded to or tolerated previous therapy. It binds with the IL-6 receptor, an immune system protein produced in increased quantities for patients with rheumatoid arthritis and has been associated with disease activity, joint destruction and other systemic problems, the company explained. Kevzara was being investigated for its ability to reduce the overactive inflammatory immune response associated with Covid-19, based on evidence of markedly elevated levels of IL-6 in critically ill patients infected with coronaviruses.

Giving details on the Sanofi-Regeneron trial, the companies said: “In the primary analysis group, adverse events were experienced by 80 per cent of Kevzara patients and 77 per cent of placebo patients. Serious adverse events that occurred in at least 3 per cent of patients and more frequently among Kevzara patients were multi organ dysfunction syndrome (6 per cent Kevzara, 5 per cent placebo) and hypotension (4 per cent Kevzara, 3 per cent placebo).”

Based on the results, the US based trial has been stopped, including in a second cohort of patients who received a higher dose of Kevzara (800 mg), the companies said, adding that detailed results would be submitted to a peer-reviewed publication later this year.

Trial design

The trail’s primary analysis group included 194 patients who were critically ill with Covid-19 and receiving mechanical ventilation at the time of enrolment, the companies said.

The Kevzara trial was designed after a small, single-arm study in China among mostly severe, febrile hospitalised Covid-19 patients found elevated IL-6 levels, and suggested that inhibiting this pathway with IL-6 blocker tocilizumab rapidly reduced fever and improved oxygenation in severe patients, allowing for successful hospital discharge.

The Phase 3 Kevzara trial was designed to evaluate this hypothesis in a large, placebo-controlled trial. The trial has been funded in part with federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), the companies said.

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