In the early days of the COVID-19 pandemic, Sanofi and Regeneron launched an ambitious plan to try out rheumatoid arthritis med Kevzara in desperately ill patients. But after early warning signs, a phase 3 flop has forced the drugmakers to can their U.S. trial.
Sanofi and Regeneron have stopped their stateside study of Kevzara in mechanically ventilated COVID-19 patients after the drug failed to prevent deaths or get patients off ventilation, among other key endpoints, the drugmakers said Thursday.
Kevzara, added to standard-of-care therapy, not only failed to better patients' condition after 22 days, but the drug's "minor positive trends" in ventilated patients were also offset by poor results in a partially enrolled subgroup that had not been ventilated at the start of treatment, the companies said.
Moreover, 80% of patients treated with the 400-milligram dose of Kevzara showed side effects compared with 77% in the standard-of-care control arm. Severe side effects, including multi-organ dysfunction and low blood pressure, were observed in 3% of Kevzara patients.
Sanofi and Regeneron said they plan to publish the full results of the study in a peer-reviewed journal.
The failure follows bad news from April, when the drugmakers said they would scale back study enrollment in the U.S. after a phase 2 precursor showed negligible results in treating "severe" COVID-19 patients requiring oxygen therapy, but not more intensive treatment. The phase 3 trial also stripped out a 200-mg dose of Kevzara, which showed little efficacy at the phase 2 stage.
With the U.S. trial closed, a non-U.S. Kevzara study will march on despite the warning signs, with results likely coming in the third quarter, the drugmakers said.
In late March, Sanofi and Regeneron dosed the first patient in the ex-U.S. arm of its phase 2/3 Kevzara study, which hoped to enroll 300 patients at sites in Italy, Spain, Germany, France, Canada and Russia.
The partners launched their global Kevzara program after a small-scale, single-arm study in China showed the drug might hold some promise in ventilated patients.
Meanwhile, another IL-6 inhibitor making the rounds, Roche's Actemra, has also posted less-than-stellar results in COVID-19 patients.
In June, a study authorized by Italy's drug regulator, Aifa, found Actemra didn’t improve patients’ severe respiratory symptoms, reduce ICU visits or cut mortality rates better than standard care. Aifa said the study was the first randomized test worldwide for Actemra in COVID-19. The study should be considered “important and conclusive” in early-stage COVID-19 pneumonia, Aifa said.
As Kevzara looks increasingly like a flop, Sanofi and Regeneron will likely lean into their second shot on goal with an antibody cocktail that entered a phase 3 preventative trial Monday.
The late-stage study, a joint effort with the National Institute of Allergy and Infectious Diseases, will enroll 2,000 U.S. patients at roughly 100 clinical sites, the drugmakers said. The companies will study the antibody cocktail's effects on slowing COVID-19 infection rates.
Meanwhile, Sanofi and Regeneron are also taking their antibody conjugate into two phase 2/3 trials to treat hospitalized and non-hospitalized COVID-19 patients in the U.S., Brazil, Mexico and Chile. The results from those studies are expected in late summer, the companies said.