While XEN1101 failed to hit the primary endpoint in a Phase II trial, the Canadian company is “actively exploring” further development of the program based on the totality of the data.
Pictured: A woman with her head in her hands/iStock, simpson33
Despite announcing Monday that its investigational treatment for major depressive disorder, XEN1101, failed to beat placebo in the Phase II X-NOVA trial, Xenon Pharmaceuticals Inc. indicated it sees a path forward for the program.
The study evaluated the efficacy, safety and tolerability of XEN1101 as a monotherapy given in 10 mg or 20 mg doses to 168 patients with moderate to severe major depressive disorder (MDD). Its primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) after six weeks of treatment, with the drug only narrowly beating placebo.
“A clear dose response and a clinically meaningful, but not statistically significant” response was observed, the company noted in a press release. This, despite early promise in the study: after one week, XEN1101 achieved statistical significance in the MADRS, “demonstrating early onset of efficacy.”
The drug did achieve statistical significance on a pre-specified endpoint, the Hamilton Depression Rating Scale, as well as in a secondary endpoint, the reduction of anhedonia—or the inability to experience pleasure—as rated by the Snaith-Hamilton Pleasure Scale. Physicians also reported “at least minimally improved symptoms of depression,” using the Clinical Global Impression of Improvement,” according to the press release.
“Based on the totality of data from this study, including clinically meaningful drug activity in depression and anhedonia, we are actively exploring the future development of XEN1101 in MDD and potentially other indications as we believe this mechanism has potential broad applicability,” Ian Mortimer, the company’s president and chief executive officer, said in a prepared statement.
In the same press release, Chief Medical Officer Christopher Kenney highlighted the “clinically meaningful, dose-dependent drug activity and early onset of efficacy in depression,” as well as the fact that the drug was well tolerated, with a low incidence of treatment-emergent adverse events, and no serious adverse events in either dose group. As such, XEN1101 “has the potential to play an important role in addressing anhedonia, a common co-morbidity in depression,” Kenney said.
This marks Xenon’s second neuropsychiatric drug candidate to come up short in recent weeks. Earlier this month, Neurocrine Biosciences announced that two of its drug candidates, NBI-91352 and NBI-1065846, failed to prove effective in focal onset seizures (FOS) and MDD, respectively. Neurocrine was investigating NBI-91352, a sodium channel inhibitor, in partnership with Xenon. Neurocrine does not plan further development of the program in FOS.
Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at lynchjourno@gmail.com.
