Omeros reports additional positive data from OMS824 Phase IIa schizophrenia clinical trial

Patients with schizophrenia were administered a higher dose than had been evaluated in any OMS824 trial, which resulted in approximately 50% higher plasma concentrations than did the previously reported highest dose and had a similar side-effect profile to those of the lower doses.

OMS824 selectively inhibits PDE10, an enzyme expressed in areas of the brain linked to a wide range of diseases that affect cognition, including schizophrenia and Huntington’s disease.

The results reported were in psychiatrically stable patients who continued their usual antipsychotic regimen and received OMS824 or placebo for 14 days. Despite achieving approximately 50% higher plasma concentrations of OMS824 than previously reached at the next-highest dose in the Phase IIa trial, OMS824 was tolerated with mild or moderate adverse events that were consistent with those seen in previous cohorts, were self-limited and did not result in any discontinuation of the drug.

The drug concentrations in these schizophrenia patients were also approximately 50% higher than levels that corresponded to an average of 66 percent target interaction (a high of approximately 70%) at PDE10 in a Phase 1 positron emission tomography (PET) trial in healthy subjects.

To date, the OMS824 PET trial has demonstrated significantly higher target interaction at PDE10 without extrapyramidal symptoms (loss of muscle control, e.g., muscle rigidity, tremors, or involuntary muscle movements) than has been reported for any other PDE10 inhibitor in development. An additional PET trial cohort is planned in the coming weeks.

The positive results across all doses tested in this Phase IIa trial indicate that OMS824 can be administered in combination with standard antipsychotic medications and that, at tolerated doses, yields plasma concentrations that are predicted to achieve a high degree of PDE10 target interaction in the striatum.

Future Phase II and Phase III clinical trials in Omeros’ schizophrenia program may evaluate OMS824 both as a single agent and as adjunctive treatment for cognitive impairment, acute exacerbation of symptoms, and/or inadequate response to antipsychotic medications.

Omeros chairman and CEO Dr Gregory A Demopulos noted the company is pleased with how OMS824 continues to perform over a wide range of dosing across multiple clinical trials — whether administered to healthy volunteers or patients with schizophrenia, the molecule has demonstrated remarkable tolerability at high plasma levels and, likely, at even higher target interaction than we have measured to date.

"We look forward to completing the PET cohort and to evaluating the compound’s efficacy in our currently enrolling Phase 2 Huntington’s trial and our ongoing Phase 2 program in patients with schizophrenia," Dr Demopulos added.

PDE10 is an enzyme that is expressed in areas of the brain linked to diseases that affect cognition and psychomotor functions, including Huntington’s disease and schizophrenia. Huntington’s disease is a hereditary neurodegenerative disorder that leads to movement, cognition, and behavioral abnormalities and premature death.

Schizophrenia is a group of severe brain disorders characterized by an abnormal interpretation of reality, which can manifest as delusions, hallucinations, and/or disordered thinking and behavior. Cognitive dysfunction is responsible for substantial disability in both of these diseases and is not meaningfully improved by current medications.

Omeros’ proprietary compound OMS824, currently in Phase II clinical programs, inhibits PDE10 and is being developed for the treatment of cognitive disorders. In addition to potential benefits on cognition, OMS824 could also improve the motor and psychiatric abnormalities in Huntington’s disease as well as the positive (for example, hallucinations) and negative (for example, flat affect) symptoms of schizophrenia.

Omeros has been awarded Orphan Drug designation by the US FDA to evaluate OMS824 in Huntington’s disease, and received Fast Track designation from the FDA for the development of OMS824 to treat cognitive impairment in Huntington’s disease. An application for Fast Track designation for the evaluation of OMS824 in schizophrenia is currently under FDA review.