Pseudobulbar Affect

November 9, 2009

Avanir reported positive results from the extension phase of the confirmatory Phase III STAR trial evaluating Zenvia for the treatment of pseudobulbar affect (PBA). Of the 253 subjects enrolled in the open-label extension trial, 235 completed the 12-week treatment period. Zenvia 30/10 mg was administered twice daily. The efficacy endpoint analysis was based on the change from baseline to end of study using the Center for Neurologic Studies Lability Scale (CNS-LS), measuring the severity and intensity of PBA. The subjects originally receiving Zenvia 30/10 mg in the double-blind phase reported a statistically significant treatment response over the course of their second 12 weeks of treatment compared to open-label baseline (p<0.0001). In addition, subjects that switched to Zenvia 30/10 mg from either Zenvia 20/10 mg or placebo achieved a statistically significant incremental improvement in their CNS-LS scores compared to baseline which was maintained over the 12-week treatment period (p<0.0001 for both groups). Avanir continued to be well tolerated.

August 17, 2009

Avanir released positive results from a phase III trial of Zenvia (dextromethorphan/quinidine) for the treatment of pseudobulbar affect (PBA). This double-blind, randomized, placebo-controlled, international study, dubbed STAR (Safety, Tolerability And Efficacy Results of AVP-923 in PBA), enrolled 326 subjects suffering from PBA secondary to either multiple sclerosis or amyotrophic lateral sclerosis. The subjects received Zenvia 30/10 mg, 20/10 mg or placebo twice daily during a three month double-blinded phase followed by a three-month open-label extension study. The primary endpoint was efficacy based on the changes in crying/laughing episode rates recorded in the patient diary. Both Zenvia 30/10 mg and 20/10 mg resulted in a statistically significant reduction in episode rates when compared to placebo (p<0.0001). At week twelve subjects in the Zenvia 30/10 mg group reported a statistically significant mean reduction of 88% from baseline in PBA episode rates (p≡0.01). A key secondary endpoint, reduction from baseline in Center for Neurologic Studies Lability Scale (CNS-LS), a measure of the frequency and severity of PBA, was also reached. Subjects receiving Zenvia 30/10 mg reported a significantly greater reduction in mean CNS-LS score compared to those who received placebo (p≡0.0002). Zenvia was well tolerated.

November 1, 2004

Avanir Pharmaceuticals reported positive results of its first phase III trial of their drug Neurodex (dextromethorphan/quinidine), for the treatment of pseudobulbar affect in patients with amyotrophic lateral sclerosis. Trial data indicated that the drug met its primary efficacy endpoint of emotional lability, producing significant improvement in CNS-LS diagnostic scale symptom severity score, compared with either of its component drugs (3.3 points greater vs. dextromethorphan, p=0.001; 3.7 points greater vs. quinidine, p<0.001). The drug also met all secondary endpoints, including reduction in affect episode incidence and improving quality of life and quality of relationship score significantly vs. the component drugs (p<0.01). Discontinuation due to adverse events with Neurodex occurred at four times the rate of dextromethorphan and three times the rate of quinidine, though adverse events were generally mild to moderate. The multicenter, randomized, double-blind, controlled, parallel, three-arm study enrolled a total of 140 ALS patients demonstrating pseudobulbar affect across 17 American sites.

Newron Pharmaceuticals has reported preliminary results of a phase II trial of ralfinamide, their non-opioid sodium-channel blocker for the treatment of neuropathic pain. Study results indicated that the drug was successful in meeting its efficacy primary endpoint, a significant improvement in score on the Visual Analogue Scale, a standard diagnostic tool, versus baseline. Secondary efficacy measures, including provoked allodynia, pin-prick test, clinical global impression and patient global impression, supported the primary finding. The primary safety endpoint was also met, with no consistent pattern of clinically relevant serious adverse events at any dosing regimen. This observer-blinded tolerability and efficacy pilot study enrolled a total of 18 patients with neuropathic pain, who received ascending oral doses of ralfinamide for 4 weeks; the trial was conducted at a single center in Austria. Newron announced plans to use these results to support future trials.

August 30, 2004

Amarin announced positive results of a gene-variant analysis of data from their phase III study of Miraxion (LAX-101), for the treatment of Huntington’s disease. Original results from the study, announced October 2002, indicated that Miraxion was not significantly more efficacious than placebo in the intent-to-treat-population, despite a positive trend towards efficacy. Post hoc analysis has shown that a subset of patients with a specific variation in the gene thought to be responsible for causing Huntington’s disease demonstrated statistically significant improvement in symptom severity scores. Amarin estimates that this polymorphic variation is present in roughly 65% of Huntington’s patients. The company has announced plans to initiate additional studies of the drug to investigate this gene-dependent efficacy.<

Avanir has reported positive results of their pivotal phase III study of Neurodex, for the treatment of pseudobulbar affect (uncontrollable laughing or crying; PBA), in patients with multiple sclerosis (MS). Study data show that the study met its primary endpoint, with patients receiving the drug achieving significant reduction in symptom severity score on the CNS-LS diagnostic scale, compared with placebo. The study also met all four of its secondary endpoints, significantly improving quality of life and quality of relationships, and significantly reducing PBA episode frequency and pain. The drug was well tolerated, with only dizziness occurring more frequently on Neurodex than placebo. The study enrolled a total of 150 MS patients across 22 sites, all of whom met pre-determined PBA-frequency inclusion criteria.

July 1, 2002

Phase II/III trial results indicate that Avanir Pharmaceuticals' Neurodex is effective in the treatment of pseudobulbar affect (emotional lability) in subjects with amyotrophic lateral sclerosis. The double-blind, controlled trial compared Neurodex to each of its two active components: dextromethorphan and an enzyme inhibitor. The primary efficacy variable, change from baseline in CNS-Lability Scale score, was statistically significant in favor of Neurodex in the intent-to-treat population.

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