Equilibre Biopharmaceuticals Announces Positive Topline Results from Phase 2 Clinical Trial of EQU-001 (NCT05063877) for Safety, Tolerability and Preliminary Efficacy as Adjunctive Therapy for Focal Seizures in Adults with Epilepsy

2023-01-30

临床结果临床2期

Median Reduction of Seizure Frequency of 35.7% Over Placebo was Achieved in the 60 mg Treatment Arm

Neurological Effects and Other Adverse Effects (AEs) Similar to Placebo

NEW YORK, Jan. 30, 2023 /PRNewswire/ -- Equilibre Biopharmaceuticals Corp., a clinical stage biopharmaceutical company focused on neurological diseases, today reported positive topline results from the Phase 2 clinical trial evaluating the clinical safety, tolerability, and preliminary efficacy of EQU-001 – a novel anti-inflammatory anti-seizure medication - administered as once-daily oral adjunctive therapy for focal seizures in adults with epilepsy.

The EQU-201 dose-ranging study demonstrated EQU-001, a novel-mechanism anti-seizure medication candidate, is safe and well tolerated at all tested doses through 60 mg QD. No treatment-related Serious Adverse Effects (SAEs) were reported, all AEs were grade 1 and 2 and AEs occurred at similar rates among treated and placebo participants. Dizziness and other AEs typical of anti-seizure medications did not occur more frequently in treated participants. Although not powered for efficacy, results show a dose-dependent decrease in per 28-day focal seizure frequency when compared to placebo with a 35.7% median reduction over placebo in the 60 mg treatment arm. In addition, a greater number of participants achieved a 50% or greater reduction in per 28-day focal seizure frequency in the 60 mg treatment arm as compared with placebo (OR 5.6, CI 0.47-66.4). The exploratory biomarker analyses demonstrated that oral administration of EQU-001 resulted in reduced IL-17 and IL-1b plasma levels compared to subject's baseline and also limited the ability of peripheral mononuclear cells (PBMCs) to secrete additional pro-inflammatory cytokines upon ex vivo stimulation. This further validates the anti-inflammatory mechanism of action of EQU-001 and its potentially beneficial impact in people with epilepsy.

"The results of the EQU-001 study are encouraging because they demonstrate impressive tolerability and encouraging efficacy for adult patients with focal epilepsy, especially for those with seizures that are difficult to treat. Patients can benefit from the easy regimen of taking one pill a day that helps reduce the occurrence of seizures without added neurological or other side effects," said Dr. Firas Fahoum, Director, Epilepsy and EEG Unit, Neurology Division, Tel Aviv Sourasky Medical Center, and the study's lead Principal Investigator.

Dr. Pavel Klein, Director of Mid-Atlantic Epilepsy and Sleep Center, Professor of Neurology at George Washington University and an Investigator on the study said, "It's important to note that while many other anti-seizure medications (ASM) work more directly via modulation of neuronal ion channels to suppress action potentials, EQU-001 has an additional, novel anti-inflammatory effect, which could represent a novel addition to our armamentarium of ASMs."

Dr. Jacqueline A. French, Professor of Neurology at NYU Grossman School of Medicine, President of the Epilepsy Study Consortium, and an investigator on the study said, "Patients living with epilepsy face the debilitating impact of focal seizures, as well as the debilitating side effects of many available medications. There is a great need for new and efficacious medications that are well tolerated by patients with fewer AEs. If in fact EQU-001 is working through a novel anti-inflammatory mechanism, this would mean that the drug is acting directly on disease pathophysiology. I am very excited to see the results of the next study."

Philip A. Barach, Equilibre's Chairman and Chief Executive Officer commented, "On behalf of the entire Equilibre team, I wish to extend our thanks to the participants, investigators, and site coordinators who made this study possible. We have generated compelling evidence of a unique safety and tolerability profile for EQU-001 as well as encouraging preliminary efficacy data. Importantly, we saw a clean neurological AE profile and reductions of focal seizures compared to placebo across cohorts, which supports continued development of EQU-001 in our multi-national EQU-202 pivotal study. With these compelling topline results, we are eager to continue to work with the FDA moving forward."

Designed as a randomized, double-blind, placebo-controlled, multicenter study in the US and Israel, the EQU-201 study (NCT05063877) was a dose-finding study that evaluated the safety, tolerability, and preliminary efficacy of EQU-001 at 10 mg, 20 mg, 40 mg, and 60 mg once daily. Although participants with generalized and unknown seizures were allowed to be included, the total number of participants with generalized seizures during the treatment period was 1 and with unknown seizures was 0, so these subsets were not analyzed. The study included a total of 43 randomized and treated participants in the safety and mITT populations. Subjects had an average age of 40.4 ± 13.14 years, and were on one, two, three, or four (9%, 33%, 40%, 19%, respectively) stable background ASMs. The median baseline seizure frequency across the study groups was 12 per 4 weeks (range 3 – 123). All 37 subjects who completed the double-blind period entered the open-label extension to evaluate the long-term safety, tolerability, and effectiveness of EQU-001.

In addition, the exploratory biomarker analysis of PBMCs and plasma samples collected over the course of 12 weeks treatment with EQU-001 confirmed its anti-inflammatory mechanism of action and showed that EQU-001 reduced the ability PBMCs to secrete pro-inflammatory cytokines in response to ex vivo stimulation. These findings were associated with a significant decrease of IL-17 and IL-1b plasma levels in EQU-001 vs placebo treated patients, with pKey Safety and Tolerability Findings:

EQU-001 was safe and well-tolerated with no treatment-related serious adverse events (SAEs). All treatment emergent adverse events (TEAEs) were grade 2 or less.

TEAEs were similar in the placebo arm (87.5% of participants) as compared with each dose arm (up to 70% of participants in the 40 mg treatment arm).

Neurological and psychological AEs were uncommon and, as with all AEs in this study, occurred in less than 10% of treated participants and were similar in treated and placebo arms. Dizziness occurred in 8.6% of treated participants, 0% of participants in the 60 mg treatment arm, and 25% of participants in the placebo arm. Fatigue occurred in 8.6% of treated participants, 22% of participants in the 60 mg treatment arm, and 25% of participants in the placebo arm.

No laboratory based TEAEs exceeded grade 1. Infections occurred more commonly in the placebo arm (37.5% vs. 11% overall and 0% in the 60 mg treatment arm).

Study completion was 88.6% across all treatment arms and 75% in the placebo arm. One subject in each of the 40 mg and 60 mg treatment arms discontinued the study due to an AE.

Key Efficacy Findings:

Although this study was designed to assess safety and tolerability of a range of doses in a real-world setting, positive efficacy data was also captured. There was an overall dose response trend with increasing median percent reductions from 10 mg through 60 mg excepting the 40 mg group. The median percent reduction (95%CI) in focal seizures per 28 days in the mITT population was 41.6% (-5.6 to 83.5), 7.4% (-51.3 to 29.1), 19.9% (-33.6 to 50.2), 12.3% (-32.1 to 83.1), and 5.8% (-110 to 36.9) in 60 mg, 40 mg, 20 mg, 10 mg, and placebo treatment arms, respectively.

A ≥50% reduction in frequency of focal seizures was achieved in 44.4% (OR 5.6, CI 0.47-66.4), 0% (not calculable), 12.5% (1.0, 0.05-19.4), 25% (2.3, 0.17-32.6), and 12.5% (reference) of participants in the 60 mg, 40 mg, 20 mg, 10 mg, and placebo treatment arms, respectively.

Key Biomarkers Findings

EQU-001 (60 mg) significantly decreased IL-17, IL-21, IFN-g and TNF-a secretion induced in PBMCs by ex vivo stimulation after 12 weeks of treatment by p2 value ranges between 0.3-0.8. The spontaneous secretion of IL-1b and TNF-a PBMC cultures was increased in placebo, but not in EQU-001-treated (60 mg) patients. The plasma levels of IL-17 and IL-1b were significantly (p

Equilibre has designed and is currently implementing EQU-202, a 300 patient, multi-center (US, EU, UK, Israel, and others) placebo-controlled three-arm study in which the 20 mg and 60 mg dose arms will be tested against placebo. Equilibre has received study-may-proceed guidance from the FDA, approval from the Ministry of Health of the State of Israel and first randomization is anticipated, in February 2023. In addition, the open-label extension for EQU-201 is ongoing and expected to generate long-term data for EQU-001.

About Equilibre Biopharmaceuticals Corp.

Equilibre is a clinical stage biopharmaceutical company developing novel treatments for patients with neurological diseases. The Company's lead candidate EQU-001 is now in large Phase 2 study as an adjunct therapy for focal epilepsy that is anticipated to be pivotal (NCT05473442). EQU-001 is also in various stages of preclinical investigation for several additional indications including seizure prophylaxis in traumatic brain injury, spasticity associated with spinal cord injury, infantile spasms, and MS. For more information, please visit: https://eqneuro.com

Forward Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on management's expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. The information contained in this press release is believed to be current as of the date of original issue. Equilibre expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

SOURCE Equilibre Biopharmaceuticals Corp