AVANIR Pharmaceuticals Submits Complete Response to FDA Approvable Letter for Zenvia in PBA
ALISO VIEJO, Calif., April 30, 2010 - AVANIR Pharmaceuticals, Inc. (NASDAQ: AVNR) today announced the submission of its Complete Response to the October 2006 Approvable Letter issued by the U.S. Food and Drug Administration (FDA) for Zenvia™ (dextromethorphan/quinidine) for the treatment of pseudobulbar affect (PBA). AVANIR expects the FDA to classify the response as a Class 2 resubmission1, which would result in an expected review period of 180 days and potential approval of Zenvia in the fourth calendar quarter of 2010.
"The filing of our Complete Response to the FDA Approvable Letter is another significant milestone for AVANIR and represents the culmination of more than three years of hard work and determination by the AVANIR team," said Keith Katkin, AVANIR's President and CEO. "With the help and guidance of the FDA, we were able to improve the benefit-risk profile of Zenvia with new low dose formulations that we believe, if approved by the FDA, can be utilized safely and effectively by patients suffering from the often disabling condition of PBA."
"We are thrilled to have filed our Complete Response with the FDA," said Randall Kaye, MD, AVANIR's Chief Medical Officer. "Our team worked diligently to compile this comprehensive Zenvia data package which addresses questions and concerns raised by FDA as quickly as possible following the completion of the STAR trial at the end of 2009. The updated regulatory filing contains approximately twice the number of patient exposures than were included in the original NDA, with over 1,600 subjects exposed and over 500 patient-years of exposure to the components of Zenvia over the past 10 years of clinical development. We believe that our response provides the FDA with the data they need to reach a favorable benefit–risk determination associated with Zenvia and that a decision on approval would be possible in the fourth calendar quarter of this year."
In the Approvable Letter of 2006, the FDA raised certain safety concerns related to the original Zenvia 30/30 mg dose formulation. After discussions with the FDA, the Company agreed to reformulate and conduct a confirmatory Phase III trial (STAR trial) under a Special Protocol Assessment (SPA) testing new lower dose 30/10 mg and 20/10 mg formulations of Zenvia designed to enhance the safety and tolerability profiles while maintaining clinically meaningful and statistically significant efficacy.
The Complete Response features an extensive data package designed to address the concerns raised in the FDA Approvable Letter. The filing consists of several modules including the final study reports from the double blind and open-label portions of the STAR trial, cardiovascular and respiratory safety white papers, an integrated safety database of subjects exposed to the components of Zenvia at any dose over the past 10 years of development, the Company's proposed package insert and a proposed REMS program.
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.
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 be disabling, 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. 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 has filed an application for regulatory approval in the PBA indication and expects an FDA approval decision in the fourth calendar quarter of 2010. 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 meet expected review timelines or approve Zenvia for any indication. 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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1 "Classifying Resubmissions of Original NDAs in Response to Action Letters" Manual of Policies and Procedures, FDA Center for Drug Evaluation and Research (CDER), 5/1/98
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Apr 30, 2010