The University of Oxford and Sound Pharmaceuticals (SPI), are pleased to announce the successful completion of a Phase 2a study testing SPI-1005 as a new treatment for bipolar disorder (BPD).
Adult BPD patients (N=60 in the Intent to Treat Analysis) with active mania or hypomania were randomized (1:1) in a double-blind trial and treated for 3-weeks with SPI-1005 or matching placebo as ‘add-on’ therapy to treatment as usual. Weekly assessments were performed including a 1-week period after the completion of study drug. The primary endpoint was difference in the Young Mania Rating Scale (YMRS) score (0-60) between SPI-1005 and placebo at the end of 21-days of treatment. The YMRS is a commonly tested measure in determining treatment effectiveness during acute manic episodes. The secondary endpoints included the Clinical Global Impression-Severity (CGI-S) scale (1-7) and the Altman Self-Rating Mania (ASRM) Scale (0-20). SPI-1005 did not require dose escalation or dose tapering, an important difference in this add-on drug strategy to the standard of care which included concomitant anti-psychotics and mood stabilizers.
After removing patients who received valproate therapy (mood stabilizer) from the analysis, SPI-1005 treated patients had a 11.8-point reduction in YMRS scores vs a 7.2-point reduction in placebo, a difference of 4.6 points (p<0.058). SPI-1005 treated patients had a 1.4-point reduction in CGI-S scores vs a. 0.7-point reduction in placebo, a difference of 0.7 (p<0.040). Improvements in depressive scale scores were also observed in the ebselen vs placebo group following 21 days of treatment. SPI-1005 was very well tolerated with only mild to moderate adverse events that were similar in incidence and severity to those observed in placebo. “The study shows important preliminary evidence of therapeutic activity for SPI-1005 in bipolar disorder. This pilot investigation has given us critical information to inform design of future trials and has confirmed the safety of SPI-1005 in a group of patients with severe mental illness taking multiple medications,” said Dr. Phil Cowen, Chief Investigator of the Oxford study and a distinguished clinician in the Department of Psychiatry.
BPD involves both manic and depressive episodes and has been difficult to treat both acutely and chronically. Lithium, a mainstay of BPD treatment including acute mania has significant dose-limiting side effects that limit its safety and effectiveness. “SPI-1005 represents a new therapeutic class with several potential neuropsychiatry indications that can treat patients with BPD in both a safe and effective manner,” said Jonathan Kil, MD, Co-Founder, CEO and CMO.
SPI-1005 is an investigational new drug that contains ebselen, a small molecule that mimics and induces the activity of Glutathione Peroxidase (GPx) in the inner ear, retina, brain, lung, and kidney. SPI-1005 represents a novel class of anti-inflammatory and is under clinical testing in several neurotologic diseases where GPx activity is reduced including sensorineural hearing loss, ototoxicity, neurotoxicity, and Meniere’s disease. In addition to these neurotologic diseases and BPD, GPx activity is thought to be diminished in several other neuropsychiatric disorders including schizophrenia and autism.
The Stanley Medical Research Institute (SMRI), a leading funder of clinical trials involving psychiatric disease, provided support for this University of Oxford clinical trial. SMRI is a nonprofit organization supporting research on the causes of, and treatments for, schizophrenia and bipolar disorder. SMRI has supported more than $550 million in research in over 30 countries. Oxford University Department of Psychiatry works in close collaboration with clinical services, particularly Oxford Health NHS Foundation Trust and the Oxford University Hospitals NHS Trust. Its leading clinical and translational academics provide a link with the world-class discovery science groups working in Oxford. The Department is committed to the translation of scientific discovery into benefits for patients. Its role is to champion patients’ interests by making basic research applicable to the causes, diagnosis, and treatment of disorders and disease. SPI is a privately held biotech in Seattle, WA developing the first medications for the prevention and treatment of hearing loss and tinnitus www.soundpharma.com. For more information regarding this UK based trial please see clinicaltrials.gov and NCT03013400.