Omeros Corporation, a clinical-stage biopharmaceutical company, announced positive data from the multiple-ascending-dose (MAD) portion of the company's phase 1 clinical trial evaluating OMS824, the lead compound in Omeros' phosphodiesterase 10 (PDE10) programme.
With these data and the previously announced successful single-ascending-dose portion of this clinical trial, Omeros is advancing OMS824 toward a phase II clinical programme. OMS824 selectively inhibits PDE10, an enzyme expressed in areas of the brain linked to a wide range of diseases that affect cognition, including Huntington's disease and schizophrenia.
The OMS824 phase I clinical trial was a randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study. The trial enrolled 64 healthy male subjects; 40 subjects received a single dose and 24 subjects received daily dosing for 7 to 10 days. OMS824 was well tolerated by all subjects, and the only apparent drug-related adverse event was mild somnolence at the highest dose evaluated. No subject had extrapyramidal symptoms (e.g., involuntary muscle movements), which are associated with marketed antipsychotic medications and have been seen with other companies' PDE10 inhibitors at levels of approximately 50-percent engagement of the PDE10 enzyme in the brain. A radiotracer imaging study is underway to confirm the target engagement of OMS824 in human brains.
The study results showed that the pharmacokinetic parameters (Cmax and AUC) increased linearly with the dose and that OMS824 had a long half-life that is consistent with once daily dosing. OMS824 was detected in the cerebrospinal fluid at the expected concentration relative to that in the blood. The drug concentration in the cerebrospinal fluid is predicted to achieve near-complete inhibition of the PDE10 target in the brain. These results show that OMS824, at well-tolerated doses, achieves concentrations that are anticipated to effectively inhibit PDE10 and support continuing development for the treatment of Huntington's disease, schizophrenia and other central nervous system disorders.
"These results are exciting – it appears that OMS824 is able to achieve significantly higher concentrations at the target enzyme in the brain than other PDE10 inhibitors being developed across the industry without incurring the movement abnormalities seen with those other compounds," stated Gregory A Demopulos, MD, chairman and chief executive officer of Omeros. "While wrapping up the phase I programme, we are aggressively advancing OMS824 into phase II trials. Our initial focus will be Huntington's disease, for which we will be requesting orphan drug as well as Fast Track designations from the FDA, and a phase IIa trial in patients with schizophrenia is expected to follow shortly thereafter. In addition to our progress in the OMS824 program, we plan to submit the NDA next quarter and the MAA mid-year for OMS302, our ophthalmic drug product, and we remain on track to advance our MASP-2 and PDE7 programs into the clinic in the coming months."
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 behavioural abnormalities and premature death. Cognitive dysfunction is responsible for substantial disability in these diseases and is not improved by current medications. Omeros' proprietary compound OMS824 inhibits PDE10 and is being developed for the treatment of cognitive disorders. In addition to potential benefits on cognition, OMS824 could also improve psychiatric manifestations, such as the positive (e.g., hallucinations) and negative (e.g., flat affect) symptoms of schizophrenia.
Omeros is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing products targeting inflammation, coagulopathies and disorders of the central nervous system.