AVANIR Announces Positive Outcome of Zenvia PK Study
"We are extremely encouraged by the positive outcome of this study," said Dr. Randall Kaye, AVANIR's Chief Medical Officer. "We have now identified a dosing regimen which, based on its observed PK parameters, we expect to demonstrate comparable efficacy with improved safety and tolerability relative to the regimens previously demonstrating efficacy in DPN pain. Notably, the new formulation of Zenvia offers a lower overall exposure to quinidine which should improve the cardiovascular risk profile. We look forward to engaging in discussions with the FDA with the goal of securing an SPA agreement for the next Phase III study protocol. In addition, the data from the PK study further reinforces our confidence in the Zenvia 30/10 mg dose being studied in our current confirmatory Phase III STAR trial in pseudobulbar affect (PBA)."
"I am very pleased that we were able to identify a new dose of Zenvia to take forward in our DPN pain program," said Keith Katkin, AVANIR's President and CEO. "In addition, this study provides us with important new information which we can use to strengthen our intellectual property protection for Zenvia. We look forward to releasing the detailed study results, including PK parameters, once we incorporate these PK findings into our Zenvia patent portfolio."
The incidence of reported adverse events was higher in dosing regimens with higher peak concentrations of dextromethorphan (DM) or its metabolite product dextrorphan (DX). No serious adverse events were reported. The most common adverse events were dizziness, headache, nausea, diarrhea, and somnolence, which were generally mild to moderate in severity and decreased over time. No new safety signals were reported, and the overall safety was similar to that observed previously. Also, there were no new QTc safety signals reported with no subject in the study exceeding a QTcF greater than or equal to 480 msec. There were no reported cardiovascular arrhythmias, no reported Torsades de Pointes and no clinically meaningful changes in cardiac repolarization. Two subjects were discontinued during the study due to pre-existing cardiovascular abnormalities.
Formal PK Study Design
The formal PK study is a single center, randomized, double-blind, placebo-controlled, parallel-group, multiple dose pharmacokinetic evaluation of various dose combinations and regimens of DM and Q. Safety was determined by evaluating vital signs, laboratory parameters, ECGs, physical examination, and by recording adverse events during the treatment period. A total of 80 subjects were randomized to receive one of the following oral dose combinations of DM/Q for 8 days (10 of the 80 subjects received placebo): 45/30 mg twice daily (BID), 30/10 mg BID, 30/10 mg three times daily (TID), 60/15 mg once daily (QD), 60/15 mg BID.
Zenvia 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 is currently in development for the treatment of pseudobulbar affect (PBA) and diabetic peripheral neuropathic (DPN) pain. In October 2006, the Company received an approvable letter for Zenvia in the treatment of PBA. The Company has initiated a confirmatory Phase III study under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA) utilizing a new lower quinidine dose formulation of Zenvia intended to address safety concerns raised in the Agency's approvable letter for Zenvia in the treatment of PBA. For more information about this trial, visit http://www.pbatrial.com and for more information about the Agency's SPA process see http://www.fda.gov/cder/guidance/3764fnl.htm. In April 2007, AVANIR announced successfully meeting all primary endpoints in a Phase III study of Zenvia in DPN pain. In May 2008 the Company released top-line results of a formal pharmacokinetic (PK) study that identified an alternative lower-dose quinidine formulation of Zenvia for DPN pain intended to deliver similar efficacy and improved safety/tolerability versus the formulations previously tested for this indication.
AVANIR Pharmaceuticals is focused on acquiring, developing, and commercializing novel therapeutic products for the treatment of chronic diseases. AVANIR's products and product candidates address therapeutic markets that include the central nervous system, inflammation, and infectious diseases. AVANIR's lead product candidate, Zenvia, is being developed for the treatment of pseudobulbar affect (PBA) and is the subject of an approvable letter from the FDA for that indication. The Company has initiated a confirmatory Phase III study under a Special Protocol Assessment (SPA) agreement with the FDA utilizing a new lower quinidine dose formulation of Zenvia intended to address safety concerns raised in the Agency's approvable letter for Zenvia in the treatment of PBA. Additionally, in April 2007 AVANIR announced meeting all primary endpoints in a Phase III clinical trial with Zenvia in patients with diabetic peripheral neuropathic (DPN) pain. In May 2008 the Company released top-line results of a formal pharmacokinetic (PK) study that identified an alternative lower-dose quinidine formulation of Zenvia for DPN pain intended to deliver similar efficacy and improved safety/tolerability versus the formulations previously tested for this indication. AVANIR has licensed the MIF inhibitor program to Novartis International Pharmaceuticals Ltd. and has sold its anthrax monoclonal antibody program to Emergent BioSolutions. The Company's first commercialized product, Abreva(R), 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.
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," 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. There can be no assurance that any additional Phase III trial for Zenvia will be successful, that any new doses of Zenvia will be safe and effective, that the U.S. Food and Drug Administration (FDA) will approve Zenvia for any indication or that the Company will be able to secure additional worldwide intellectual property protection for its Zenvia patent portfolio. There can be no assurances that Zenvia clinical development programs for indications other than pseudobulbar affect will move forward without additional capital or partnerships. There can also be no assurance that the proceeds from the Company's recently completed offering of common stock and warrants will be sufficient to fund our clinical trials to completion as expected or to fund operations through the expected timing of an approval decision from the FDA. 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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Eric Benevich or Brenna Mullen
Posted: May 2008