Additional Zenvia Phase III results in multiple sclerosis announced by AVANIR

AVANIR Pharmaceuticals, Inc.Oct 9 2009

AVANIR Pharmaceuticals, Inc. (NASDAQ:AVNR) today announced additional detailed results from the confirmatory double-blind Phase III STAR trial evaluating two doses of the investigational drug Zenvia™ (dextromethorphan/quinidine) compared to placebo in the treatment of pseudobulbar affect (PBA) among patients with underlying multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). Over the course of the 12-week study in the MS patient subset, Zenvia 30/10 mg met the primary efficacy endpoint by reducing PBA episode rates by an incremental 11.9% beyond placebo.

Efficacy Highlights – MS Cohort:

• Zenvia 30/10 mg dose met the primary endpoint in the subset of patients with underlying MS by significantly reducing PBA episode rates compared to placebo
• Both Zenvia groups demonstrated a numerical reduction in mean CNS-LS scores but did not achieve statistical significance versus placebo in this small subset of MS patients
• Zenvia 30/10 mg demonstrated relief of MS-related pain in the subset of MS patients with moderate-to-severe pain

“PBA represents an area of high unmet medical need with no FDA-approved treatments currently available. Although the involuntary emotional outbursts of PBA cause considerable impairment for millions of individuals in the United States, it is under recognized and commonly misdiagnosed,” said poster presenter Daniel Wynn, MD, Director, Clinical Research, Co-Director, Consultants in Neurology Multiple Sclerosis Center and STAR Trial Steering Committee member. “If approved, Zenvia will be an important treatment option to ameliorate the profound distress caused by PBA among individuals afflicted with neurologic disease or injury and their caregivers.”

“We were very pleased that Zenvia demonstrated significant improvement in PBA episodes in the MS sub-population as well as encouraging proof of concept data in MS-related pain,” said Randall Kaye, MD, AVANIR’s Chief Medical Officer. “This is especially exciting given that the STAR trial was not powered to detect an efficacy signal in such a small number of patients. These data provide additional insight into the clinical utility of Zenvia and help shape our plans for future drug development.”

ADDITIONAL EFFICACY RESULTS

An important pre-specified secondary endpoint was the reduction of pain associated with MS using the 11-point Pain Rating Scale (PRS). All MS patients enrolled in the study assessed their daily pain regardless of baseline pain level or use of concomitant analgesics. Mean pain scores in MS patients (all patients regardless of baseline pain score) were decreased from baseline across time in the Zenvia 30/10 mg group. Mean scores at days 15 and 29 showed trends for superiority of Zenvia 30/10 mg over placebo>

An additional secondary endpoint analysis was based on the change from baseline to end of study using the Center for Neurologic Studies Lability Scale (CNS-LS). The CNS-LS is a validated instrument measuring the frequency and severity of PBA, where a higher score indicates more severe PBA. Results from this secondary endpoint are summarized in the following table:

SAFETY AND TOLERABILITY RESULTS

Overall, Zenvia was generally safe and well tolerated in the MS population. In the MS subset, the percent of patients completing the study was 93.3% for Zenvia 30/10 mg, 89.7% for Zenvia 20/10 mg, and 86.7% for placebo. Only 3 MS patients discontinued the study because of adverse events; all were in the Zenvia 20/10 mg group. One MS patient in the Zenvia 30/10 mg group and 2 MS patients in the placebo group reported non-fatal serious adverse events (SAEs). The most common adverse events among MS patients that were more frequent in the Zenvia groups than for placebo were dizziness, nausea, diarrhea, somnolence and nasopharyngitis.

CONCLUSIONS

• Overall, Zenvia 30/10 mg and 20/10 mg were effective, safe, and well-tolerated for treatment of patients with PBA. The new formulation of Zenvia appeared to demonstrate comparable efficacy with a potentially improved safety and tolerability profile, compared with formulations of higher doses.
• In this trial, PBA episodes were frequent and severe in patients with underlying MS. Zenvia was well-tolerated in this subset and Zenvia 30/10 mg was significantly superior to placebo for decreasing PBA episode rate, despite the small size of the subset.
• Zenvia 30/10 mg demonstrated relief of MS-related pain in the subset of patients with moderate-to-severe pain.