|Avanir presenting top-line data this week|
|By Chris Fields, Special Report Correspondent|
|Monday, 12 April 2010 03:00|
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 is Zenvia. Zenvia (dextromethorphan/quinidine) is a combination therapy that has completed a confirmatory Phase III trial in the treatment of pseudobulbar affect (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 for which there is no FDA approved therapies. It is estimated to affect approximately 2 million patients in the U.S. with moderate to severe PBA.
In three Phase III studies, Zenvia was generally safe and well tolerated . Zenvia met its endpoints demonstrating statistically significant efficacy by reducing PBA episodes, as well as other secondary endpoints.
The STAR Trial was a multicenter-randomized, double-blind, three arm parallel, placebo controlled study of 326 ALS and MS patients diagnosed with PBA, Zenvia 30/10mg and Zenvia 20/10mg provided a statistically significant reduction of PBA episode rates over the course of the study compared to placebo (p<0.0001). At week 12 (end of study), patients in the Zenvia 30/10 mg group reported a statistically significant mean reduction of 88% from baseline in PBA episode rates compared to placebo (p=0.01). Overall, both doses of Zenvia were generally safe and well tolerated in the study.
At the upcoming AAN Meeting
"The first Zenvia data poster will be presented on Tuesday, April 13, between 3:00 p.m. and 7:30 p.m. Eastern Daylight Time (EDT). The poster will feature efficacy data from the 12-week, open label extension study of Zenvia in the treatment of patients with pseudobulbar affect (PBA) and was selected by the American Academy of Neurology as part of the Late-Breaking Science program. These abstracts that qualify for Late-Breaking Science presentations must be of sufficient scientific importance or interest to warrant expedited presentation and publication."
The accepted late-breaker poster is:
Poster number P02.295: PERSISTENT EFFICACY OF DEXTROMETHORPHAN (DM)/QUINIDINE (Q) FOR PSEUDOBULBAR AFFECT (PBA): RESULTS FROM A 12-WEEK, OPEN-LABEL EXTENSION (OLE) STUDY
The second presentation includes two Zenvia data posters and will take place on Thursday, April 15, between 3:00 p.m. and 7:30 p.m. EDT. The posters will feature cardiac safety data from the double-blind phase of the STAR trial and safety and tolerability data from the open label extension study of Zenvia in the treatment of patients with PBA.
The accepted posters are:
Poster number P06.119: SUMMARY OF CARDIAC SAFETY FROM A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF DEXTROMETHORPHAN/QUINIDINE (STAR) FOR TREATMENT OF PSEUDOBULBAR AFFECT
Poster number P06.128: SAFETY AND TOLERABILITY OF DEXTROMETHORPHAN/QUINIDINE FOR PSEUDOBULBAR AFFECT IN A 12-WEEK OPEN-LABEL EXTENSION STUDY
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.
In the FDA Approvable Letter and from the original 30/30 mg dose there were many issues addressed by the FDA. With the SPA, the new dose was a 30/10mg Dose in the STAR trial.
Below are the concerns from the Approvable Letter and the answers to them from the STAR trial in the Special Protocol Assessment (SPA).
1) Concern: -Potential for QT interval prolongation
Answer: -New low dose formulations reduced quinidine exposure by 67%, reduced QTc outliers & should increase margin of cardiac safety
- No clinically meaningful changes in QTc, no pro-arrhythmic and no cardiovascular SAEs were seen in STAR trial
2) Concern: -Rate of AEs in “vulnerable” ALS population
Answer: Substantial reduction in rates of common AEs (nausea, dizziness, fatigue, etc.) compared to what was reported previously
3) Concern: -Potential for increased risk of falls
Answer: No difference b/w Zenvia 30/10 mg and placebo reported Incidence of falls
4) Concern: -Potential for respiratory depression in ALS
Answer: -No acute de-compensation of respiratory function observed after initiation of study drug
-Full analysis of nocturnal O2 saturation showed no difference versus placebo
Key Issues addressed from the STAR TRIAL with the FDA…..
-STAR was designed to address issues raised in FDA approvable letter.
-Avanir agreed to reformulate & test lower doses of Zenvia
-Conducted STAR confirmatory Phase III trial under an SPA (Special Protocol Assessment). A Special Protocol Assessment is a binding agreement with the FDA that the Phase III trial protocol design, clinical endpoints, planned conduct and statistical analyses are acceptable to support regulatory approval.
This data that will be presented from April 13th -15th at the AAN meeting is key for AVANIR. From these presentations this week it is expected that they will plan 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. This week will be a big week for Avanir at the American Academy of Neurology so investors have a lot to look forward to. This meeting can really be a breakthrough not only for AVANIR but their shareholders as well.
Disclosure: Long AVNR