AVANIR Pharmaceuticals Presents Zenvia Long-Term Efficacy Data at AAN Annual Meeting Late Breaking Science Program

ALISO VIEJO, Calif.--(BUSINESS WIRE)--Apr 13, 2010 - AVANIR Pharmaceuticals, Inc. (NASDAQ: AVNR) today announced long-term efficacy data from the 12-week double-blind phase and the 12-week open-label extension phase of the confirmatory Phase III STAR trial evaluating Zenvia™ (dextromethorphan/quinidine) in the treatment of pseudobulbar affect (PBA) in patients with underlying multiple sclerosis or amyotrophic lateral sclerosis. The detailed efficacy data were presented at the American Academy of Neurology (AAN) Annual Meeting in Toronto and were selected by the AAN as part of the Late-Breaking Science program. (Poster number: P02.295)

LATE BREAKER POSTER HIGHLIGHTS

 

  • Zenvia 30/10 mg demonstrated persistent long-term efficacy and tolerability as a therapy for PBA with 92.9% of patients completing the 12-week treatment period of the open-label extension study
  • Patients who continued on Zenvia 30/10 mg or titrated up from Zenvia 20/10 mg to Zenvia 30/10 mg demonstrated statistically significant incremental improvement in their CNS-LS scores at end of study compared to open-label baseline (p<0.0001 for both groups)
  • Patients originally on placebo in the double-blind phase who initiated Zenvia 30/10 mg in the open-label phase demonstrated statistically significant improvement in their CNS-LS scores at end of study compared to open-label baseline (p<0.0001)
  • At the last study visit (Day 84) of the open-label extension, the mean CNS-LS score was below the cut-off value indicative of clinical PBA

“We are very pleased that the Zenvia long-term efficacy data were selected for inclusion in the Late-Breaking Science program by the AAN,” said Randall Kaye, MD, AVANIR's Chief Medical Officer. “These data demonstrate that the new low-dose 30/10 mg formulation of Zenvia provides persistent long-term efficacy by significantly reducing the frequency and severity of PBA episodes over a six-month period. This was the first time that the efficacy of Zenvia has been studied beyond three months and we were very pleased to see such a durable response over the extended treatment period.”

PATIENT DISPOSITION AND ADDITIONAL EFFICACY RESULTS

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. In general, the open-label cohort resembled the groups in the preceding double-blind phase of the trial. Patients enrolled in the open-label extension study within two weeks of completing the double-blind phase. Therefore, some patients were off study drug at the time of entering the open-label extension. All patients that enrolled in the open-label extension received Zenvia 30/10 mg twice daily; once in the morning and once in the evening. A total of 235 patients (or 92.9%) completed the open-label study.

During the open-label extension phase, the assessment of efficacy was exploratory and measured by 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 severity and intensity of PBA. In the open-label assessment of efficacy, CNS-LS scores continued to improve over the 12-week extension study and patients previously on placebo were the most incrementally improved. The efficacy results in all treatment groups and at comparable time points evaluated in both phases of the STAR trial are summarized in the table below:

Mean CNS-LS Scores Over Time: Double Blind and Open Label Phases of the STAR Trial

 

    Double-Blind Phase   Open-Label Phase
Study Visit   Zenvia 30/10 mg

N = 110

 

  Zenvia 20/10 mg

N = 107

 

  Placebo N = 109

 

  Zenvia 30/10 mg N = 253

 

Baseline   19.8   21.0   19.9   13.8
Day 84   11.8   12.8   14.3   11.2
Mean Change   -8.2   -8.2   -5.7   -2.7
p-value (day 84 versus baseline)   p <0.0001   p <0.0001   N/A   p <0.0001
ITT Population – All patients received Zenvia 30/10 mg in the open label study; lower scores indicate better response

 

In the open-label extension, patients originally receiving Zenvia 30/10 mg in the double-blind phase demonstrated statistically significant incremental improvement in their CNS-LS scores over the second 12 weeks of treatment compared to open-label baseline (p<0.0001). In addition, patients who switched to Zenvia 30/10 mg from either Zenvia 20/10 mg or placebo also achieved a statistically significant incremental improvement in their CNS-LS scores compared to baseline (p<0.0001 for both groups). The efficacy results of the open-label study are summarized in the table below:
Mean CNS-LS Scores Over Time in Open-Label Phase

 

    Total Open-Label Group   By Original Treatment Cohort
Study Visit   Zenvia 30/10 mg

N = 253

 

  Zenvia 30/10 mg N = 94

 

  Zenvia 20/10 mg N = 76

 

  Placebo N = 83

 

Open-Label Baseline   13.8   13.4   13.7   14.4
Visit 2 (day 15)   11.1   10.8   11.9   10.6
Visit 3 (day 42)   11.1   10.7   11.9   10.9
Visit 4 (day 84)   11.2   10.8   11.3   11.5
Mean Change   -2.7   -2.6   -2.4   -3.1
p-value (day 84 versus baseline)   p <0.0001   p <0.0001   p <0.0001   p <0.0001
ITT Population – All patients received Zenvia 30/10 mg in the open label study; lower scores indicate better response; open-label baseline scores differ from the end of the double-blind as some patients stopped receiving therapy between the final double-blind visit and the open-label baseline visit

 

CONCLUSIONS

 

  • In the open-label phase, Zenvia 30/10 mg continued to improve CNS-LS scores over the additional 12-week treatment period demonstrating that the new low-dose formulation provides long-term efficacy as a treatment for reducing the frequency and severity of PBA.

ABOUT ZENVIA

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.

ABOUT 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 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.

ABOUT AVANIR

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.

To be included on AVANIR's e-mail alert list; click on the link below or visit AVANIR's website:
http://www.b2i.us/irpass.asp?BzID=958&to=ea&s=0.

Contact: AVANIR Pharmaceuticals, Inc.
INVESTOR CONTACTS
Eric Benevich or Brenna Mullen
949-389-6700
ir@avanir.com

 

Posted: April 2010

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