Disappointing Phase III for Kiniksa’s COVID-19 Antibody

Shares of Kiniksa Pharmaceuticals plunged 15.1% in premarket trading after the company announced its Phase III COVID-19 monoclonal antibody mavrilimumab failed to hit its primary endpoint.

Bermuda-based Kiniksa’s mavrilimumab is an investigational, fully human monoclonal antibody. It is designed to target granulocyte macrophage colony stimulating factor receptor alpha (GM-CSFRα) and specifically bind to the alpha subunit of the GM-CSF receptor.

The company had been assessing mavrilimumab as a potential therapeutic for COVID-19-related acute respiratory syndrome (ARDS). Specifically, the Phase II/III study was examining the safety and efficacy of the monoclonal antibody for use in adult patients who did not require mechanical ventilation and had hypoxia and severe COVID-19 pneumonia/hyperinflammation.

The Phase III portion of the study included 582 participants. They were randomized to receive either a 6 mg or 10 mg intravenous dose of mavrilimumab or placebo. The primary endpoint of the Phase III study was the proportion of patients alive and free of mechanical ventilation 29 days following infusion.

Sanj K. Patel, chairman and chief executive officer of Kiniksa Pharmaceuticals, expressed disappointment at the study outcome and voiced his pride in the company’s efforts to combat the ongoing COVID-19 pandemic.

“We greatly appreciate the participation of the patients, their families, the investigators, and the Kiniksa employees who made this study possible,” Patel said.

Patel noted that the company continues to believe in mavrilimumab’s potential and broad utility and will evaluate the next steps in its development program. Prior to aiming mavrilimumab at COVID, the company has been assessing the monoclonal antibody at rheumatoid arthritis.

In a Phase IIb study in Europe, mavrilimumab demonstrated its efficacy and safety. In addition to rheumatoid arthritis, the company is studying the molecule as a potential therapeutic for giant cell arteritis.

In a Phase II study in this indication, mavrilimumab achieved both the primary and secondary efficacy endpoints with statistical significance. Mavrilimumab was granted Orphan Drug designation for the treatment of GCA in 2020 by the U.S. Food and Drug Administration.

And while the company will continue to assess the potential of the monoclonal antibody, the Kiniksa CEO added that its primary strategy is to focus on its Arcalyst franchise.

Arcalyst, initially discovered by Regeneron and licensed by Kiniksa, is a subcutaneously injected recombinant dimeric fusion protein designed to block IL-1 alpha and IL-1 beta signaling. Arcalyst has been approved for recurrent pericarditis, cryopyrin-associated periodic syndromes, including Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome. It has also been greenlit for deficiency of IL-1 receptor antagonists.