Jan 8, 2020—Celon Pharma ($CLN.PL) today announced positive top-line results from a Phase II study of Falkieri (proprietary esketamine dry powder inhalation) in acute phase of treatment-resistant bipolar depression.
In the trial, Falkieri met the primary endpoint with statistically significant reductions in MADRS total score compared to placebo at Week 2 in all tested doses, with a dose-response trend. MADRS placebo-subtracted differences were -5.9 (95% CI: -10.2 to -1.5; p=0.009) in the 24 mg dose; -6.7 (95% CI:- 11.1 to -2.2; p=0.004 ) in the 36 mg dose and -8.2 (95% CI: -12.6 to-3.7; p<0.001 ) in the 48 mg dose.
This was a randomized, double-blind, placebo-controlled, multi-center study of 88 adult patients with an inadequate response to at least two evidence-based treatment lines in bipolar depression. Patients were allocated to receive adjunctive treatment of either 24 mg, 36 mg, or 48 mg of Falkieri or placebo twice weekly for two weeks.
“We are extremely pleased with the robustness of the data from our Phase 2 trial, demonstrating that Falkieri shows real promise for patients with treatment-resistant bipolar depression, a highly debilitating condition with very few effective and approved therapeutic options. This is highly important because majority of people with bipolar depression exhibit chronic and refractory course” said Maciej Wieczorek, PhD, Celon Pharma's CEO and Head of Research & Development. “Falkieri uses an inhaled esketamine and is designed to be self-administered by qualified patients at home as a maintenance treatment, thus avoiding the need for regular hospital visits. We look forward to meeting with the U.S. Food and Drug Administration and European Medicines Agency to discuss initiating a Phase 3 program in 2021 and in parallel to actively seek partners to commercialize this exciting product.”
Patients randomized to Falkieri treatment also demonstrated significant improvement in another depressive scale - HDRS at all tested doses., with dose-response effect trend.
Positive results were also observed for multiple secondary endpoints with the most impressive remission rates at Week 2 achieving levels of 43-46% on active treatment vs. 9% in the placebo arm.
In this Phase 2 study, Falkieri exhibited good safety and tolerability profile. No discontinuations due to adverse events were observed. There were also no serious adverse events (SAEs) occurred in the study. Dissociation was transient, self-limiting and mild in intensity achieving its peak at 45 minutes after drug administration. No sedation was recorded.
Importantly, manic switch was not seen in patients administered Falkieri in the study, being first such observation demonstrated in esketamine trials. Mania induction is a well-recognized risk factor of antidepressant therapeutics in bipolar depression.
Full data from the Phase 2 trial will be presented at an upcoming medical conference.
“The results of this study provide firm evidence the esketamine by inhalation may represent a novel approach to adjunctive treatment for patients suffering from treatment-resistant bipolar depression, replicating rapid-acting antidepressant effect observed in major depressive disorder. Esketamine’s new mechanism of action, albeit yet not fully understood, may provide additional benefit for patients who do not adequately respond to mood stabilizers approved in bipolar depression treatment,” said Professor Wieslaw J. Cubala, M.D., Medical University of Gdansk, trial investigator. “In bipolar depression chronic and refractory course of the disease is commonly seen with limited number options available. The magnitude of the effect seen in this study, combined with a favorable safety and tolerability profile, provides evidence that adjunctive therapy with esketamine in the Falkieri dry powder inhalation device may be developed as an important beneficial treatment strategy in treatment-resistant bipolar depression in the forthcoming phase III studies. Moreover, this trial results is thrilling as it is the first phase II study with esketamine in this indication focusing on the unmet needs brought by the medical professionals, regulatory, and, above all, the patients.”
About the 03KET2018 study
03KET2018 was a Phase 2, two-week, randomized, double-blind, placebo-controlled, multi-center study that evaluated efficacy, safety and tolerability of Falkieri, esketamine administered by dry powder inhalation, in three doses (24 mg, 36 mg and 48 mg) as an adjunctive treatment in patients with bipolar depression in 88 patients who had an inadequate response to a stable dose of at least two treatments with proven efficacy in bipolar depression
Conference Call and Webcast Information
Celon Pharma will discuss top-line results from its Phase 2 trial of Falkieri for adjunctive treatment of patients with treatment resistant bipolar depression via videoconference call on Jan 11, 9.00 CET time.
Webcast for English speakers is available here: Webcast