AVANIR Pharmaceuticals Presents Zenvia Phase III Safety Data at the American Academy of Neurology Annual
ALISO VIEJO, Calif., April 15, 2010 - AVANIR Pharmaceuticals, Inc. (NASDAQ:AVNR) today announced the presentation of detailed data, including safety and tolerability data from the open-label extension as well as cardiac safety data from the double-blind phase of the Phase III confirmatory STAR trial evaluating the investigational drug Zenvia™ (dextromethorphan/quinidine) in the treatment of pseudobulbar affect (PBA). The data were presented in two posters at the American Academy of Neurology (AAN) Annual Meeting in Toronto, Canada.
"We are pleased to present these important data at the AAN Annual Meeting and are very satisfied with the safety and tolerability profile that Zenvia demonstrated in both the double-blind and open-label extension phases of the STAR trial," said Randall Kaye, MD, AVANIR's Chief Medical Officer. "The new lower dose formulations of Zenvia have maintained statistically significant and clinically meaningful efficacy while providing an improved safety and tolerability profile relative to the original higher dose formulation. We plan to file our full response with the FDA within the next few weeks and expect an approval decision on the PBA application before the end of this year."
POSTER HIGHLIGHTS: SAFETY AND TOLERABILITY – OPEN-LABEL EXTENSION
In PBA patients treated for up to 24 weeks (12 double-blind
weeks and 12 open-label weeks) Zenvia 30/10 mg was generally safe
In the open label extension of the STAR trial, no new safety concerns emerged
SAFETY AND TOLERABILITY OF ZENVIA IN OPEN LABEL STUDY (Poster Number: P06:128)
Of the 283 patients completing the 12-week double-blind phase of the STAR trial, 253 patients (or 89.4%) entered the open-label extension; 94 who originally received Zenvia 30/10 mg, 76 who originally received Zenvia 20/10 mg and 83 who originally received placebo. Demographically and by underlying disorder, the open-label cohort resembled the groups in the preceding double-blind phase of the trial. All patients enrolled into the open-label study within two weeks of completing the double-blind phase and received the Zenvia 30/10 mg dose twice daily. A total of 235 patients (or 92.9%) completed the open-label study.
POSTER HIGHLIGHTS: CARDIAC SAFETY – DOUBLE BLIND
In patients receiving either Zenvia 30/10 mg or 20/10 mg, mean
changes in QTc interval were < 5 msec
In patients receiving either Zenvia 30/10 mg or 20/10 mg, no absolute or change in QTc exceeded 500 msec or 60 msec respectively and no new cardiac safety signals emerged
In the STAR trial there were no reports of pro-arrhythmic events or cardiovascular serious adverse events (SAEs)
SUMMARY OF CARDIAC SAFETY FROM STAR TRIAL (Poster Number: P06:119)
The STAR trial was a 12-week, double-blind, confirmatory Phase III trial of Zenvia in the treatment of PBA in patients with underlying multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). The STAR trial compared active treatment with Zenvia 30/10 mg and Zenvia 20/10 mg to placebo. At baseline and on days 15, 29, 57, and 84 (end of study), 12-lead ECGs were obtained. QT-interval length was calculated with correction for heart rate by Bazett's formula and by Fridericia's formula (QTcB and QTcF). At baseline, the treatment groups had similar demographics, similar PBA severity and similar QTc interval length. In all treatment groups, mean changes in QTcB and QTcF were <5 msec. No patients had QTc intervals >500 msec at day 84, and no patients had increases >60 msec in either QTcB or QTcF.
Copies of the posters are available on the Company's website at www.avanir.com. Copies can also be obtained from the Company by request at 101 Enterprise, Suite 300, Aliso Viejo, CA 92656.
Zenvia™ (dextromethorphan/quinidine) is a combination of two well-characterized compounds: the therapeutically active ingredient dextromethorphan and the enzyme inhibitor quinidine, which serves to increase the bioavailability of dextromethorphan. This first-in-class drug candidate is believed to help regulate excitatory neurotransmission in two ways: through pre-synaptic inhibition of glutamate release via sigma-1 receptor agonist activity and through postsynaptic glutamate response modulation via uncompetitive, low-affinity NMDA antagonist activity. Zenvia has completed a confirmatory Phase III trial in the treatment of pseudobulbar affect (PBA) and has successfully completed a Phase III trial for diabetic peripheral neuropathic (DPN) pain. In October 2006, the Company received an FDA approvable letter for Zenvia in the treatment of PBA. The Company conducted the confirmatory Phase III STAR trial under a Special Protocol Assessment (SPA) agreement with the FDA with the goal of addressing safety concerns raised in the Agency's approvable letter for Zenvia in the treatment of PBA. AVANIR plans to file a full response to the approvable letter in the second calendar quarter of 2010, with an FDA approval decision expected in the fourth calendar quarter.
Pseudobulbar affect (PBA) is a neurologic condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying in patients with underlying neurologic disease or injury. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state. In addition to the burden of the underlying neurologic disorder, PBA can have a number of problematic individual and socially disabling consequences, which may depend upon the frequency and severity of the laughing and crying episodes. The etiology of PBA is not completely understood but the symptoms of PBA are similar across patient populations. The pathophysiology of PBA is widely believed to involve injury to the neurologic pathways that regulate affect. PBA is estimated to occur in 49% of patients with ALS, in 10% of patients with MS, in 11% of patients 1 year after suffering a stroke, and in 11% of patients after a traumatic brain injury. PBA has also been reported secondary to a number of other neurologic conditions. There are currently no FDA approved treatments for PBA. Further information about pseudobulbar affect can be found at www.PBAinfo.org.
AVANIR Pharmaceuticals, Inc. is a biopharmaceutical company focused on acquiring, developing, and commercializing novel therapeutic products for the treatment of central nervous system disorders. AVANIR's lead product candidate, Zenvia, has completed a confirmatory Phase III trial in the treatment of pseudobulbar affect (PBA) and has successfully completed a Phase III trial for diabetic peripheral neuropathic (DPN) pain. AVANIR plans to file an application for regulatory approval in the PBA indication in the second calendar quarter of 2010, with an FDA approval decision expected in the fourth calendar quarter. AVANIR sold its anthrax monoclonal antibody program to Emergent BioSolutions. The Company's first commercialized product, Abreva® (docosanol), is marketed in North America by GlaxoSmithKline Consumer Healthcare and is the leading over-the-counter product for the treatment of cold sores. Further information about AVANIR can be found at www.avanir.com and further information about pseudobulbar affect can be found at www.PBAinfo.org.
FORWARD LOOKING STATEMENTS
Statements in this press release that are not historical facts, including statements that are preceded by, followed by, or that include such words as "estimate," "intend," "anticipate," "believe," "plan," "goal," "expect," "project," or similar statements, are forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from the future results expressed or implied by such statements. For example, there can be no assurance that the U.S. Food and Drug Administration (FDA) will approve Zenvia for any indication, or that the Company will meet projected timelines. Risks and uncertainties affecting the Company's financial condition and operations also include the risks set forth in AVANIR's most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and from time-to-time in other publicly available information regarding the Company. Copies of this information are available from AVANIR upon request. AVANIR disclaims any intent to update these forward-looking statements.
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Posted: April 2010