The primary endpoint of the trial was based on the daily diary entries for the Pain Rating Scale as defined in the Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). In the trial, two doses of Zenvia, 45/30 mg DMQ dosed twice daily ("DMQ 45") and 30/30 mg DMQ dosed twice daily ("DMQ 30"), were compared to placebo based on daily patient diary entries for the Pain Rating Scale. Both Zenvia treatment groups had lower pain ratings than placebo patients (p less than 0.0001 in both cases). In the DMQ 45 patient group, average reductions were significantly greater than placebo patients at Days 30, 60, and 90 (p less than 0.0001 at each time point). In the DMQ 30 patient group, average reductions were also significantly greater than placebo patients at Days 30 and 60 (p less than 0.0001) and Day 90 (p=0.007).
Zenvia also demonstrated statistically significant improvements in a number of key secondary endpoints including the Pain Relief Ratings Scale and the Pain Intensity Ratings Scale. The secondary endpoints compared the baseline value to the average rating values at each study visit after randomization. The average pain relief reductions as measured on the Pain Relief Rating Scale were greater for the DMQ 45 patient group (p=0.0002) and for the DMQ 30 patient group (p=0.0083), compared with placebo. In addition, the DMQ 45, but not the DMQ 30, patient group demonstrated statistically significant improvements in the Pain Intensity Rating Scale compared with placebo (p=0.029). Although not powered to detect differences in the seconda ry endpoint of Peripheral Neuropathy Quality of Life Scale Composite score, the DMQ 45 patients showed a greater improvement than placebo patients (p=0.05) and the DMQ 30 patients showed a greater improvement than placebo patients (p=0.08).
Overall, the safety data from this study are consistent with data from previous studies. The most commonly reported adverse events were dizziness, nausea, diarrhea, fatigue and somnolence and were generally mild to moderate in nature. A higher number of patients in the DMQ 45 and DMQ 30 treatment groups (25.2% and 21.0%, respectively) discontinued due to an adverse event than compared to placebo (11.4%). There were no significant differences in serious adverse events with 7.6%, 4.8% and 4.1% reported in the DMQ 45, DMQ 30 and placebo groups, respectively. In addition, no deaths occurred throughout the study. Further safety and efficacy analyses are on-going and are expected to be presented at an upcoming public medical forum.
"We are extremely encouraged by the results of this trial which are consistent with Avanir's prior Phase II study in patients with diabetic neuropathic pain," said Randall Kaye, MD, Senior Vice President and Chief Medical Officer of Avanir Pharmaceuticals. "We look forward to meeting with the FDA to discuss the next study for Zenvia for the treatment of diabetic neuropathic pain given the robustness of the clinical results."
"Current treatment options are either partially effective or don't work at all for more than one-half of people suffering from diabetic neuropathic pain. The results of this study provide additional evidence that Zenvia, if approved, may be a safe and effective treatment option for the millions of Americans suffering from diabetic neuropathic pain," said Keith A. Katkin, President and CEO of Avanir Pharmaceuticals. "Avanir now has two Phase III Zenvia programs in areas with significant unmet medical need, one in Involuntary Emotional Expression Disorder (IEED) and on e in diabetic neuropathic pain. We look forward to the continued development of Zenvia for these two important indications. As previously stated, the company plans on initiating a confirmatory clinical trial in IEED with a new, lower quinidine dose formulation later this year," he added.
The company has scheduled a conference call for today, Wednesday, April 18, 2007 at 10:30 AM ET. Keith Katkin, President and CEO of Avanir, and Randall Kaye, MD, Senior Vice President and Chief Medical Officer, will discuss the results of this Phase III study. The call-in number is (877) 558-3407 for domestic and (706) 679-1941 for international callers, and the conference ID number is 6342812.
If you cannot attend the live broadcast, a webcast will be available online until May 18, 2007 at www.avanir.com. A telephone replay is available until April 23, 2007 and can be accessed by dialing (800) 642-1687 domestic and (706) 645-9291 international, and entering the conference ID number 6342812.
About Diabetic Neuropathic Pain
Diabetic neuropathic pain, one of the most debilitating forms of pain, is caused by nerve damage that can result from diabetes. It is often described as burning, tingling, stabbing, or pins and needles in the feet, legs, hands or arms. An estimated 3.5 million people in the United States experience diabetic neuropathic pain according to the American Diabetes Association.
About the Study
In 2005 AVANIR initiated a randomized double-blind, placebo-controlled, phase III clinical trial testing two doses of Zenvia in patients with painful diabetic neuropathy to assess efficacy, and overall safety and tolerability. The study was conducted at 40 sites in the US and Israel and was fully enrolled with 379 patients randomized across the three treatment arms (45 mg dextromethorphan / 30 mg quinidine BID dose, 30 mg dextromethorphan / 30 mg quinidine BID dose and placebo). The protocol for the study was reviewed and approved by the U.S. Food and Drug Administration (FDA) through a special protocol assessment (SPA). The Company expects this to be the first of two pivotal studies required for the approval of Zenvia in the treatment of diabetic neuropathic pain.
Zenvia is a combination of two well-characterized compounds, the active ingredient dextromethorphan, and the enzyme inhibitor quinidine, which serves to increase the bioavailability of dextromethorphan. The 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 Involuntary Emotional Expression Disorder (IEED) and diabetic neuropathic pain.
In October 2006, the Company received an approvable letter for the treatment of Zenvia in IEED. To address safety concerns raised in the FDA's approvable letter for Zenvia for the treatment of IEED, the company intends to initiate a confirmatory phase III study with a new lower quinidine dose formulation of Zenvia. The Company is considering whether it would be necessary or advisable to study a similar lower dose of quinidine in the second phase III trial being planned for diabetic neuropathic pain.
Avanir Pharmaceuticals is focused on developing, acquiring 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 currently markets FazaClo(R), the only orally-disintegrating formulation of clozapine for the management of severely ill schizophrenic patients who fail to respond adequately to standard schizophrenic drug treatments. FazaClo is als o indicated for reducing the risk of suicidal behavior in patients with schizophrenic or schizoaffective disorder. For full prescribing information and important safety information regarding FazaClo, please visit www.fazaclo.com. Avanir's lead product candidate for the treatment of involuntary emotional expression disorder (IEED), Zenvia(TM), is the subject of an approvable letter from the FDA. Avanir has licensed certain compounds to Novartis International Pharmaceutical Ltd. for the treatment of inflammatory disease. 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 Statement
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 the Company will receive FDA regulatory approval for Zenvia for any indication. Final review decisions made by the FDA and other regulatory agencies concerning are often unpredictable and outside the influence and control of the Company and it is possible that the FDA could disagree with the Company's interpretation of clinical trial results. Risks and uncertainties 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 th ese forward-looking statements.
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