FDA accepts NDA for lurasidone, a treatment for schizophrenia

Dainippon Sumitomo Pharma America announced that the FDA has accepted for filing the New Drug Application (NDA) submitted for lurasidone for the treatment of schizophrenia. This submission includes data from more than 40 clinical studies involving more than 2,500 lurasidone-treated patients. In four of these studies, lurasidone demonstrated significantly greater improvement versus placebo on the primary efficacy measure, the Positive and Negative Syndrome Scale (PANSS) total score, at study endpoint.

Lurasidone is an investigational, atypical antipsychotic with high affinities for dopamine D(2), serotonin 5-HT(7), 5-HT(2A), 5-HT(1A), and noradrenaline alpha(2C) receptors and minimal-to-no affinity for histamine H(1) or cholinergic M(1) receptors.

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Lurasidone (SM-13,496) is an atypical antipsychotic developed by Dainippon Sumitomo Pharma which is currently pending approval for the treatment of schizophrenia and bipolar disorder in the United States.  It has completed Phase III clinical trials and an NDA was recently (as of December 30, 2009) submitted to the FDA.

Lurasidone acts as a D2 (Ki = 1.68 nM), 5-HT2A (Ki = 2.03 nM), 5-HT7 (Ki = 0.495 nM), and α2C-adrenergic (Ki = 10.8 nM) receptor antagonist, and 5-HT1A (Ki = 6.75 nM) receptor agonist.[4] It has only weak or negligible actions at the 5-HT2C, α1-adrenergic, H1, and mACh receptors.

In clinical studies, lurasidone alleviates both positive (e.g., hallucinations, delusions) and negative (e.g., apathy, emotional withdrawal) symptoms of schizophrenia without inducing extrapyramidal side effects, despite its potent D2 antagonistic actions.  It has a relatively well-tolerated side effect profile, with low propensity for extrapyramidal symptoms, QTc interval changes, and weight-, lipid-, and glucose-related adverse effects. Side effects reported in at least 5% of subjects and at least twice the frequency of placebo include akathisia (17.6% vs 3.1% placebo), somnolence (11.7% vs 5.5%), parkinsonism (6.8% vs 0%), and weight gain (5.1% vs 2.4%).

Lurasidone may be exceptionally useful for treating cognitive and memory deficits seen in schizophrenia for several reasons: 1) unlike many other antipsychotics, lurasidone does not block the muscarinic acetylcholine receptors, an action well-known to impair learning and memory; 2) lurasidone has prominent activity at 5-HT1A, 5-HT2A, 5-HT7, and α2C-adrenergic receptors, all of which have been implicated in enhancement of cognitive function if modulated properly; 3) due to its low liability for extrapyramidal symptoms, lurasidone is unlikely to require coadministration of anticholinergics, which impair cognition in their own right. Indeed, in animal studies, lurasidone was found to be superior to all of the other antipsychotics examined in reversing dizocilpine-induced learning and memory impairment, including risperidone, olanzapine, quetiapine, clozapine, aripiprazole, and haloperidol.

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Dainippon Sumitomo Pharma America, Inc. (DSPA), a U.S. subsidiary of Dainippon Sumitomo Pharma Co., Ltd. (DSP), today announced that the U.S. Food and Drug Administration (FDA) recently accepted for review the lurasidone New Drug Application (NDA) for the treatment of patients with acute schizophrenia. The NDA was submitted to FDA on December 30, 2009 and will receive a standard review.

“We are pleased that the lurasidone NDA has been accepted for review by the FDA,” said Masayo Tada, president and chief executive officer, Dainippon Sumitomo Pharma Co., Ltd. “We look forward to the potential lurasidone may bring as it represents our commitment to developing therapies that provide clear value to patients and health care professionals.”

The lurasidone NDA includes data from more than 40 clinical studies involving more than 2,500 lurasidone-treated patients. The efficacy and safety of lurasidone were evaluated in five six-week, placebo-controlled studies, involving hospitalized patients with schizophrenia. In four of these studies, lurasidone demonstrated significantly greater improvement versus placebo on the primary efficacy measure, the Positive and Negative Syndrome Scale (PANSS) total score, at study endpoint. In all five studies, lurasidone was well-tolerated and associated with limited weight gain or changes in metabolic parameters. In addition, patients treated with lurasidone exhibited mild changes in movement disorder parameters and prolactin levels.

Lurasidone is an atypical antipsychotic agent with a unique chemical structure. Lurasidone has high affinity for dopamine D(2), serotonin 5-HT(2A) and serotonin 5HT(7) receptors where it has antagonist effects. In addition lurasidone is a partial agonist at the serotonin 5HT(1A) receptor. It has no appreciable affinity for histamine or muscarinic receptors.

SOURCE Dainippon Sumitomo Pharma America, Inc.