Authors :
Presenting Author: Firas Fahoum, MD – Tel Aviv Sourasky Medical Center
Pavel Klein, M.D. – Mid-Atlantic Epilepsy and Sleep Center, Maryland; Asfi Rafiuddin, D.O. – Northeastern Regional Epilepsy Group; Claude Steriade, M.D. – NYU Langone Health; Robert Wechsler, M.D., Ph.D., FAES, FAAN – Consultants in Epilepsy and Neurology PLLC; Michael Sperling, M.D. – Farber Institute for Neuroscience (Thomas Jefferson University Hospitals); Felix Benninger, M.D. – Rabin Medical Center; Nathan Fountain, M.D. – UVA Health (University of Virginia Medical Center); Dana Ekstein, M.D., Ph.D. – Hadassah Medical Organization; Nicola Maggio, M.D., Ph.D. – Chaim Sheba Medical Center; Alexandra Zanin-Zhorov, Ph.D. – Equlibre Biopharmaceuticals B.V., Amsterdam, Netherlands; Samuel Waksal, Ph.D. – Equlibre Biopharmaceuticals B.V., Amsterdam, Netherlands, Graviton Bioscience Corporation; George Dranitsaris, Ph.D. – Equlibre Biopharmaceuticals B.V., Amsterdam, Netherlands; Ya-El Mandel-Portnoy, Ph.D., MSc – Equlibre Biopharmaceuticals B.V., Amsterdam, Netherlands; Amy Melsaether, M.D. – Equlibre Biopharmaceuticals B.V., Amsterdam, Netherlands
Rationale:
EQU-001 is a new proprietary formulation of an antiparasitic medication, currently under clinical investigation for the treatment of seizures in adults with epilepsy. A placebo-controlled, double-blind, randomized, ascending dose trial was conducted to identify the maximum tolerated dose, up to 60 mg per day, for 12 weeks, followed by an ongoing optional open label extension (NCT05063877).
Methods:
Adults (18-60 years old who signed written informed consent) in Israel and USA with epilepsy who had uncontrolled seizures while taking one to four anti-seizure medications, were screened, underwent a four weeks baseline period during which a minimum of three countable, observable seizures were required, and were then sequentially enrolled into one of four dose cohorts (10 mg, 20 mg, 40 mg, 60 mg) and randomized (4 to 1) to EQU-001 or a matched placebo and dosed for 12 weeks. Although generalized and focal seizures were allowed, too few generalized seizures occurred during the trial for meaningful analysis. Safety was reviewed by the safety review committee after the 10th patient in each cohort had been treated for 14 days to determine whether the next cohort could be opened. The primary objective was to assess the safety of a range of doses of EQU-001 as an adjunctive therapy. Secondary endpoints included assessment of preliminary efficacy (median percentage change in overall seizure counts per 28 days by treatment cohort relative to baseline and percentage of patients who had a ≥ 50% reduction in seizure frequency).
Results:
A total of 43 adult participants (aged 20 years to 69 years, mean 40.4 years) were randomized into one of the five cohorts. EQU-001 was well tolerated at all dose levels. 88.6% of treated participants and 75% of the placebo group completed the 12-week treatment period. There were no treatment-related SAEs. All treatment emergent adverse events (TEAEs) grade two 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). No TEAEs, including neurological or psychological, occurred in >10% of treated participants. Dizziness occurred in 8.6% of treated participants and 12.5% of participants in the placebo arm. Fatigue occurred in 8.6% of treated participants and 25% of participants in the placebo arm. EQU-001 demonstrated clinical activity, particularly at the 60 mg dose (results for mITT population presented).
Conclusions:
Over 12-weeks of continuous therapy, EQU-001 demonstrated excellent safety profile and 60 mg daily dose of EQU-001 was able to induce clinically meaningful reductions in focal seizure frequency in adults with epilepsy. These findings warrant further study of EQU-001 in a randomized trial in a larger patient population.
Funding:
This study (NCT05063877) was funded by Équilibre Biopharmaceuticals B.V.