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September 03, 2007
New Schizophrenia Medication Shows Early Positive Test Results
Read more... Schizophrenia Medications in Development
A new study published in the scientific journal Nature Medicine has demonstrated that a new medication in early testing helps reduce the symptoms of schizophrenia, potentially without the side effects that are common in existing schizophrenia medications. The study was sponsored by Eli Lilly and Company. The new drug that is in testing is at least three to four years from completing regulatory (FDA) review, after which, if it passes, it would be made available to for sale and use.
The New York Times reported today that "Lilly will begin a larger clinical trial for the drug this month. If that trial confirms the results seen so far, the new drug could mark a breakthrough in the treatment of schizophrenia — and open the way to a broad new class of treatments for the disease."
Unlike many other most other types of schizophrenia drugs, the Lilly compound works not by targeting dopamine, a chemical found in a person's brain, and one of the key neurotransmitters that is involved in schizophrenia. Rather, this new drug influences glutamate levels, which is a brain chemical necessary for learning and memory that is also known to be involved in schizophrenia.
This is just the second of the three phase FDA approval process - so its too soon to know if this drug will eventually make it to market, or be effective in the long term treatment of schizophrenia. However, it is a hopeful sign that progress is being made in the search for better treatments for schizophrenia.
In this study - a randomized, double-blind, placebo-controlled clinical trial - patients were assigned to four weeks of treatment with either Lilly's investigational compound LY2140023; olanzapine, an atypical antipsychotic medication that targets dopamine and serotonin receptors as an active control; or placebo. The study demonstrated that:
-- LY2140023 and olanzapine showed statistically significant improvement versus placebo in PANSS (Positive and Negative Syndrome Scale), the most common scale used for measuring symptoms of patients with schizophrenia. Both groups showed a rapid response, within one week.
-- Treatment with LY2140023 was not observed to have certain adverse events that often occur with currently approved schizophrenia medications, including increased prolactin elevations, extrapyramidal symptoms (involuntary movements or muscle stiffness), or weight gain.
-- Overall, LY2140023 40 mg given twice daily was found to be safe and well-tolerated, although no testing was done on the longer term side effect profile of the medication.
Some early side effects that were seen in this early test included insomnia, affect lability (mood changing), nausea, headache, somnolence (drowsiness, or sleepiness) and blood creatine phosphokinase increase. The adverse event profile of LY2140023 did not include prolactin increase or worsening of extrapyramidal symptoms (EPS). Although mood lability seems to represent the most important potential adverse event, it should be noted that this outcome was observed primarily at one clinical site. In the olanzapine group, treatment-emergent adverse events included elevation in blood triglyceride levels, insomnia, weight gain, somnolence, akathisia, agitation and periodontitis.
"These data provide compelling new evidence that mGlu2/3 receptor agonists have antipsychotic properties and may provide a completely new therapeutic approach for treating schizophrenia and, perhaps, other neuropsychiatric disorders," said Steven Paul, M.D., Lilly's executive vice president of science and technology. "Additional and longer-term studies are needed to confirm and extend these exciting initial findings. However, these data suggest that LY2140023 may provide a new alternative for the treatment of this often devastating condition."
The trial was a proof of concept study designed to determine LY2140023 superiority versus placebo. Olanzapine was used as an active control. 196 patients with schizophrenia were randomly assigned to LY2140023 (40 mg twice daily), olanzapine (15 mg daily) or placebo. All participants were hospitalized to ensure patient safety, tapered off from any pre-trial antipsychotic medications (no therapeutically stable patients were included in the trial), and treated in a double-blind manner for four weeks. In all, 118 patients completed four weeks of the planned study treatment.
Treatment with LY2140023 or olanzapine resulted in statistically significant improvement in PANSS (Positive and Negative Syndrome Scale) total score compared to placebo , After four weeks of treatment, the study showed that both the LY2140023 group and the olanzapine group demonstrated significantly greater response rates compared to the placebo group. Response was measured primarily by the PANSS, the most common scale used for measuring symptoms of patients with schizophrenia. A patient showing a 25% or more decrease in PANSS total score was defined as a responder. Additionally, a mean 0.51-kg weight reduction from baseline was observed in the LY2140023 group. A moderate but statistically significant weight gain was observed in the olanzapine group relative to the placebo group.
Results showed that the placebo arm experienced the highest rate of study discontinuation due to lack of efficacy, however, discontinuation due to adverse events was not significantly different across the three treatment groups.
LY2140023 is an investigational drug from Lilly, which is being developed as a new treatment option for schizophrenia. LY2140023 is an oral "prodrug," meaning it is devoid of intrinsic biological activity and, once administered, is metabolized to provide the active mGlu2/3 receptor agonist called LY404039. Most currently approved antipsychotic medications work by affecting the neurotransmitters dopamine or serotonin. For LY2140023, the active substance, LY404039, is thought to work by reducing the presynaptic release of another neurotransmitter, glutamate, in brain regions where mGlu2/3 receptors are expressed. Further studies are planned or are ongoing to learn more about the safety and effectiveness, including determining an optimal therapeutic dose for LY2140023.
Additional Related Stories:
LY2140023: Progress in Schizophrenia Treatment? (Corpus Callosum Blog)
Schizophrenia trials 'promising' (BBC News)
Source of Press Release: Eli Lilly
Posted by szadmin at September 3, 2007 11:51 AM
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