Diseases and Products | MN-305 (Anxiety Disorders)

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Disease Overview:

Generalized Anxiety Disorder (GAD) is a disorder characterized by the presence of excessive, uncontrollable anxiety and worry about two or more life circumstances, for six months or longer, accompanied by some combination of restlessness, fatigue, muscle tension, irritability, disturbed concentration or sleep, and somatic symptoms. Children or adolescents with GAD often worry a lot about things such as future events, past behaviors, social acceptance, family matters, their personal abilities, and/or school performance.  Anxiety disorders have a significant negative impact on quality of life and psychosocial functioning.

The main goal of pharmacotherapy in GAD is to treat the chronic worry and tension rapidly with agents that have few adverse effects and limited potential for abuse.  A variety of pharmacologic agents may be used to manage patients with anxiety disorders. Benzodiazepines, including Valium® (diazepam), Librium® (chlordiazepoxide), and Xanax® (alprazolam) were initially introduced as treatments for acute anxiety, but quickly found their way into chronic use. In the late 1980s, BuSpar® (buspirone), a 5-HT1A receptor partial agonist, was introduced and became very commercially successful despite a gradual onset on action. BuSpar is well known for exceptional tolerability and a benign safety profile.

Starting in the late 1990s, newer antidepressants, notably the selective serotonin reuptake inhibitors (SSRIs) and the serotonin-norepinephrine reuptake inhibitors (SNRIs), were introduced into the anxiety treatment marketplace. While effective, these antidepressants are associated with serious side effects, including agitation, insomnia and sexual dysfunction. Also, the SSRIs and SNRIs may take weeks to exert a beneficial effect.

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Market Overview:

More than 40 million Americans suffer from anxiety disorders. Generalized Anxiety Disorder (GAD) affects about 6.8 million people each year, panic disorder about 6 million, social phobia roughly 15 million, obsessive-compulsive disorder 2.2 million, and post-traumatic stress disorder about 7.7 million. Annual physician office visits for anxiety exceed 13 million; psychotherapeutic agents account for over $28 million in sales.

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MN-305 for the Treatment of Generalized Anxiety Disorder:

MN-305 is a novel, orally bioavailable compound under development for the treatment of GAD. A highly selective and potent serotonin 5-HT1A agonist, MN-305 exhibits pharmacologic characteristics that resemble those of the azapirones, of which buspirone (BuSpar®) is typical. Unlike most 5-HT1A agonists, MN-305 is not an azapirone derivative, which typically yields 1-(2-pyrimidinyl) piperazine (1-PP) upon oxidative dealkylation. It has been hypothesized that 1-PP may be responsible for interfering with the therapeutic effects of azapirones like buspirone.

MN-305 was consistently effective in a variety of preclinical models of anxiety. Its efficacy was equivalent to that of buspirone and diazepam in these models. MN-305 was 30- to 100- times more potent than buspirone. There was evidence to suggest that the onset of effect of MN-305 might be more rapid than that of other agents. In addition, MN-305 was evaluated in an extensive preclinical toxicology program which demonstrated no evidence of mutagenicity, antigenicity and carcinogenicity and in clinical safety and pharmacokinetic studies which demonstrated that it was consistently well tolerated.

In an open-label early Phase II study, patients with a variety of anxiety disorders were treated with MN-305. MN-305 provided anxiolytic efficacy without producing any tolerability or safety issues.

In June 2006, MediciNova initiated a randomized, double-blind, placebo-controlled multi-center Phase II/III clinical trial of MN-305 for the treatment of GAD. The trial evaluated the effects of 10 weeks of treatment in patients randomized to 2 flexible dosing regimens of 0.5 to 6 mg/day, 1 to 12 mg/day or placebo. The primary efficacy outcome measure was the change from baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score. In June 2006, MediciNova reported results from this trial of MN-305 in 416 patients with GAD. Trends for improvement in all efficacy outcome measures were observed in patients treated with MN-305. Statistically significant improvements in the HAM-A total score and in item 1 of the HAM-A (anxious mood) were observed through eight weeks of treatment with MN-305; however, statistical significance on the primary outcome measure of the trial (change from baseline in the HAM-A total score at week 10) was not achieved. MN-305 was well tolerated at all doses in the trial.

We will limit our development efforts on MN-305 for the treatment of psychiatric disorders to those activities necessary to maximize MN-305’s value while pursuing a variety of initiatives to monetize this product candidate.

 

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