The 60 mg treatment group had a median reduction in seizure frequency of 35.7% over placebo
Neurological effects and other adverse effects (AEs) similar to placebo
New York, January 30, 2023 /PRNewswire/ — Equilibre Biopharmaceuticals Corp., a clinical-stage biopharmaceutical company focused on neurological disorders, today announced EQU-001, a novel anti-inflammatory antiepileptic drug – once-daily treatment for focal seizures in adults with epilepsy. It is administered as an oral adjunctive therapy to
A dose-ranging study of EQU-201 demonstrated that EQU-001, a novel mechanism antiepileptic drug candidate, was safe and well tolerated at all doses tested up to 60 mg QD. No treatment-related serious adverse reactions (SAEs) were reported, all AEs were grades 1 and 2, and AEs occurred in similar proportions between treated and placebo participants. Dizziness and other adverse events typical of antiepileptic drugs did not occur more frequently in treated participants. Although not enhanced for efficacy, results showed a dose-dependent reduction in focal seizure frequency per 28 days when compared to placebo, with a median reduction of 35.7% over placebo in the 60 mg treatment group. Additionally, more participants experienced a 50% or greater reduction in focal seizure frequency per 28 days in the 60 mg treatment group compared to placebo (OR 5.6, CI 0.47-66.4). An exploratory biomarker analysis showed that oral administration of EQU-001 reduced plasma levels of IL-17 and IL-1b compared to baseline in subjects, and peripheral mononuclear cells (PBMCs) were associated with additional pro-inflammatory The ability to secrete cytokines was also demonstrated to be restricted. ex vivo stimulation. This further validates the anti-inflammatory mechanism of action of EQU-001 and its potentially beneficial effects in patients with epilepsy.
“The results of the EQU-001 study are encouraging as they show excellent tolerability and promising efficacy in adult patients with focal epilepsy, especially those with difficult-to-treat seizures. You can benefit from a simple regimen of taking one tablet daily, which helps reduce the incidence of seizures without adding neurological or other side effects. Firas FahumDirector of the Epilepsy and EEG Unit, Department of Neurology, Tel Aviv Soulaski Medical Center, and Principal Investigator of this study.
Doctor Pavel KleinDirector of the Mid-Atlantic Epilepsy and Sleep Center, Professor of Neurology George Washington University The investigators in this study noted, “While many other antiepileptic drugs (ASMs) act more directly through modulation of neuronal ion channels to inhibit action potentials, EQU-001 has additional It is important to note that it has a novel anti-inflammatory effect, which could be a new addition to our ASM arsenal.”
Doctor Jacqueline A. FrenchProfessor of Neurology at the NYU Grossman School of Medicine and president of the Epilepsy Research Consortium, investigator of the study, said: There is a great need for new and effective drugs that are well tolerated by patients with fewer adverse events. I am very excited to see the results of the next study. ”
Philip A. BarajaEquilibre’s Chairman and CEO commented: Encouraging Profile and Preliminary Efficacy Data of EQU-001. Importantly, the entire cohort showed a distinct neurological AE profile and reduction in focal seizures compared to placebo. With these compelling top-line results, we look forward to continuing to work with the FDA to move forward. ”
Randomized, double-blind, placebo-controlled, 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. and participants with unexplained seizures were allowed to be included, but because the total number of participants with generalized seizures during the treatment period was 1 and no participants with unexplained seizures, these subsets were not analyzed. did not. The study included a total of 43 randomized, treated participants in the safety and mITT populations. Subjects had a mean age of 40.4 ± 13.14 years and had 1, 2, 3, or 4 (9%, 33%, 40%, and 19%, respectively) stable background ASM. The median baseline seizure frequency for the entire study group was 12 per 4 weeks (range 3-123). All 37 subjects who completed the double-blind period participated in an open-label extension to assess the long-term safety, tolerability and efficacy of EQU-001.
Furthermore, exploratory biomarker analysis of PBMC and plasma samples collected during 12 weeks of treatment with EQU-001 confirmed its anti-inflammatory mechanism of action, suggesting that EQU-001 secretes pro-inflammatory cytokines in response. It has been shown to reduce the potency of PBMC.To ex vivo stimulation. These findings were associated with significant decreases in IL-17 and IL-1b plasma levels in EQU-001 versus placebo-treated patients, p<0.05 and p<0.01, respectively.
Summary of results
Key Safety and Tolerability Findings:
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Neurological and psychological AEs were rare and, like all AEs in this study, occurred in <10% of treated participants and were similar between treatment and placebo groups. Dizziness occurred in 8.6% of treated participants, 0% of participants in the 60 mg treatment group, and 25% of participants in the placebo group. Fatigue occurred in 8.6% of treated participants, 22% of participants in the 60 mg treatment group, and 25% of participants in the placebo group.
Key efficacy findings:
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This study was designed to assess the safety and tolerability of different doses in real-world settings, but positive efficacy data were also obtained. There was an overall dose-response trend with an increasing median rate of reduction from 10 mg to 60 mg, with the exception of the 40 mg group. The median (95% CI) reduction 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 the 60 mg, 40 mg, 20 mg, 10 mg, and placebo treatment groups, respectively.
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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) reduced focal seizure frequency by ≥50% . ), and 12.5% of participants in the 60 mg, 40 mg, 20 mg, 10 mg, and placebo treatment groups, respectively (see).
Key biomarker findings
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EQU-001 (60 mg) significantly reduced PBMC-induced IL-17, IL-21, IFN-g, and TNF-a secretion. ex vivo Stimulation after 12 weeks of treatment is p < 0.05, p < 0.01, p < 0.01, and p < 0.05, respectively. A strong correlation was observed between changes in seizure frequency and her PBMC secretion of pro-inflammatory cytokines.2 Values range from 0.3 to 0.8. Spontaneous secretion of IL-1b and TNF-a PBMC cultures were increased in placebo but not in EQU-001 treated (60 mg) patients. Plasma levels of IL-17 and IL-1b were significantly (p<0.01) decreased in patients treated with EQU-001 (60 mg) compared to predose levels. Finally, plasma levels of IL-17 and IL-1b were significantly decreased in EQU-001 versus placebo-treated patients, p<0.05 and p<0.01, respectively.
Equilibre designed and is currently implementing EQU-202. This is his 300 patient multicenter (US, EU, UK, Israel, and others) placebo-controlled, three-arm study testing 20 mg and 60 mg dose arms against placebo. Equilibre has received guidance from the FDA to proceed with research and has received approval from the US Department of Health. State of Israel The first randomization is scheduled for February 2023. Additionally, an open-label extension of EQU-201 is underway and is expected to generate long-term data for EQU-001.
About Equilibre Biopharmaceuticals Corp.
Equilibre is a clinical-stage biopharmaceutical company developing new treatments for patients with neurological disorders. Our lead candidate, EQU-001, is currently in a large Phase 2 study as an adjunctive treatment for the anticipated pivotal focal epilepsy (NCT05473442). EQU-001 is also in various stages of preclinical research for several additional indications, including seizure prevention 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. It is – Forward-looking statements are based on management’s expectations and involve certain factors that could cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. , subject to risks and uncertainties. The information contained in this press release is believed to be current as of its original publication date. Equilibre reserves the right to update or revise any forward-looking statements contained herein to reflect changes in our expectations thereon or changes in events, conditions or circumstances on which such statements are based. expressly disclaims any obligation or promise to release to
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