Omeros has announced positive results from a phase IIa clinical trial of OMS824, the company's phosphodiesterase 10 (PDE10) inhibitor, in which the drug was well-tolerated and demonstrated comparable systemic pharmacokinetics when administered alone and concomitantly with approved antipsychotic agents in patients with schizophrenia. 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.
In this phase IIa randomized, double-blind, placebo-controlled trial, OMS824 was administered at two dose levels for two weeks to psychiatrically stable patients whose antipsychotic medications were temporarily discontinued or who continued their usual antipsychotic regimen. The trial enrolled 33 patients, and the results showed that OMS824 was well-tolerated, with mild or moderate adverse events that were self-limited and resolved during the treatment period. The tolerability and pharmacokinetics of OMS824 were not affected by concomitant antipsychotic medications, allowing the drug to be developed as both a monotherapy and as adjunctive therapy in combination with currently approved antipsychotics. The plasma concentrations of OMS824 in the high-dose cohort were similar to levels that corresponded to greater than 60% target occupancy of PDE10 in a phase I positron emission tomography (PET) trial. Given the small sample size, efficacy conclusions cannot be drawn but the data support continued development in schizophrenia and other neuropsychiatric conditions.
The positive results from this phase IIa trial suggest that dose adjustment will not be necessary when OMS824 is administered in combination with standard antipsychotic medications. 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.
"PDE10 is a novel target for the treatment of schizophrenia and other neuropsychiatric disorders with the potential to address limitations of current therapy," said Michael Davidson, M.D., professor in the Department of Psychiatry, Sackler School of Medicine, Tel Aviv University, Israel. "Inhibition of PDE10, which is a novel mechanism of action, may be able to treat not only the positive symptoms in schizophrenia but also the negative symptoms and cognitive impairment. The OMS824 data are the most promising of any PDE10 inhibitor, and I am eager to review additional clinical data for Omeros' drug product."
Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros, said, "Based on the favorable tolerability and pharmacokinetics of OMS824, we are considering evaluating additional higher dose levels in patients with schizophrenia. The data from the current trial open the door to developing OMS824 as monotherapy or in conjunction with other antipsychotics for schizophrenia and a wide range of other psychiatric and neurologic disorders."
In addition to its schizophrenia program, Omeros expects to begin enrollment this quarter in a phase II clinical trial evaluating OMS824 in patients with Huntington's disease.