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New Drugs Online Report for dextromethorphan + quinidine
Information
Generic Name:
dextromethorphan + quinidine 
Trade Name: Nuedexta 
Synonym: AVP-923, Neurodex, Zeniva, Zenvia 
Entry Type: New formulation  
 
Developmental Status
UK: Approved (Licensed) 
EU: Approved (Licensed) 
US: Launched 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Jun 13: Approved in the EU [20] 
26/06/2013 17:03:44
Apr 13: EU positive opinion for Nuedexta for treatment of pseudobulbar affect [19]. 
26/04/2013 12:20:23
Mar 13: Filed in EU October 2011. The company submitted responses addressing the EMA´s "Day-120" question, and anticipates receipt of an opinion on its MAA from the CHMP in the first quarter of 2013 [18] 
27/03/2013 14:42:51
Oct 11: EU MAA filed for Neudexta for the treatment of pseudobulbar affect, a neurologic condition which is characterised by frequent outbursts of involuntary crying or laughing [16]. 
09/05/2012 10:51:44
Jan 11: Launched in US [15]. 
03/02/2011 18:23:45
Oct 10: Approved in US for the treatment of pseudobulbar affect. It will be marketed under the trade name NUEDEXTA™[14] 
01/11/2010 11:11:59
May 10: Avanir has submitted its Complete Response to the October 2006 Approvable Letter from the FDA. Avanir expects the FDA to classify the response as a Class 2 resubmission, which would result in an expected review period of 180 days and potential approval of Zenvia in 4Q 2010 [13]. 
24/05/2010 18:02:05
FDA decision expected 2H 2010 (11). 
25/01/2010 17:13:40
Filed in US Jun 05(1). Approvable letter received from US Oct 06, a new NDA was submitted in Jan 06 (2). Positive top-line PIII results (3).  
 
Trial or other data
Sep 10: The PIII STAR trial has been e-published in the Annals of Neurology (http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8249/earlyview)  
16/09/2010 18:27:32
Apr 10: Cardiac safety data from the PIII STAR trial were presented in two posters at the American Academy of Neurology Annual Meeting. 283 patients completed a 12-week double-blind phase and 253 patients entered the open-label extension. At baseline, the treatment groups had similar demographics, similar PBA severity and similar QTc interval length. At the end of the double-blind phase, mean changes in QTcB and QTcF were <5 msec in all treatment groups. No patients had QTc intervals >500 msec at day 84, and no patients had increases >60 msec in either QTcB or QTcF. No new cardiac safety signals emerged in the extension study and there were no reports of pro-arrhythmic events or cardiovascular serious adverse events [12]. 
18/04/2010 19:02:15
Dec 09: Further results from the STAR study. In Amyotrophic Lateral Scleroris (ALS) subset of pts (n=197), Zenvia (30/10mg and 20/10mg) achieved main efficacy outcome by significantly reducing pseudobulbar affect (PBA) episode rates vs. placebo (62.9% and 63.4% incremental reductions in PBA vs. placebo over study course). Reported that 90.8%, 77.9% and 85.9% of ALS patients completed the 12-week double-blind study phase in the Zenvia (30/10 mg), Zenvia (20/10 mg) and placebo groups, respectively. (10) 
11/12/2009 08:40:39
Nov 09: Company report results from the 12-week open-label extension phase of the PIII STAR. Of 283 patients who completed the double-blind phase, 253 enrolled in the extension all of whom received Zenvia 30/10 mg twice daily. Efficacy was assessed at baseline and during subsequent clinic visits using the CNS-LS score. There was a significant incremental improvement in CNS-LS scores irrespective of treatment received in the first 12 weeks, and the drug was generally safe and well tolerated with 92.9% of patients completing the extension study. There were 3 deaths in the open-label study in patients with ALS; they were attributed to respiratory failure. The company say that they will file a complete response early in 2Q 10, with an FDA approval decision expected 6 months later [9].  
10/11/2009 21:47:23
Oct 09: Detailed results from PIII STAR study reported by the company. Both the Zenvia 30/10mg and 20/10mg groups met the primary endpoint by demonstrating a significant reduction in daily PBA episode rates vs. placebo group. In addition, in the Zenvia groups there was a greater proportion of patients with complete remission of PBA episodes, a higher % of days that were episode-free, a greater proportion of patients who achieved response thresholds of 50%, 75% and 90% improvement and a greater mean reduction from baseline in CNS-LS score vs placebo. Zenvia 30/10mg demonstrated statistical superiority in time to onset of clinically meaningful effect, greater mean improvement in SF-36 Mental Health Summary scores and greater mean improvement in Beck Depression Inventory scores vs placebo. In an additional analysis of the primary endpoint pre-specified in the protocol, the % of patients who achieved and maintained complete episode remission during the last 14 days of the study was 76% in the Zenvia 30/10mg group, 80% in the 20/10mg group and 61% in the placebo group (p=0.0024 and p=0.0001) [8]. 
26/10/2009 19:19:49
Oct 09: Additional results reported from the PIII STAR trial evaluating two doses of Zenvia vs placebo in the MS patient subset (n=129). Zenvia 30/10mg reduced PBA episode rates by 11.9% over placebo (p=0.028). The lower dose Zenvia 20/10mg was not significantly different vs placebo. Zenvia 30/10mg demonstrated relief of MS-related pain in patients with moderate-to-severe pain. There was no significant difference between groups on the Center for Neurologic Studies Lability Scale (CNS-LS) [7]. 
10/10/2009 17:31:30
Oct 09: Avanir has obtained a new patent on Zenvia that will extends its commercial exclusivity period to 2025 [6]. 
07/10/2009 21:07:12
Aug 09: Company announced that the 12 week double-bline phase of the PIII STAR study met the primary endpoint (reduction in self-reported in crying/laughing episode rates): Zenvia 30/10 mg provided a 47.2% incremental reduction in episode rates vs placebo (p<0.0001). Zenvia 20/10 mg also provided a statistically significant incremental reduction of episode rates vs placebo (p<0.0001) [5].  
24/08/2009 10:21:29
Confirmatory PIII STAR trial - enrolling pts with emotional lability secondary to multiple sclerosis or amyotrophic lateral sclerosis. Double-blind phase will be followed by a three month open-label extension study. The primary efficacy endpoint will be the change in crying/laughing episodes per day (4) 
23/07/2008 12:01:07
(1) Company looking for partners for EU. PIII resulst published Neurology 2006;59(5):780-87;  
 
Evidence Based Evaluations
EPAR  http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002560/human_med_001652.jsp&mid=WC0b01ac058001d124 
   
References  
Available only to registered users
Category
BNF Category:
Central nervous system (04)
Pharmacology: Dextromethorphan (NMDA antagonist/sigma agonist) +quinidine (CYP2D6 inhibitor)  
Epidemiology: Prevalence of pathological emotions (pseudobulbar affect) following stroke is 14.9% [7].  
Indication: Pseudobulbar affect  
 
Method(s) of Administration
Oral 
 
Company Information
Name: Jenson 
US Name: Avanir 
 
NICE Information
Anticipated Commissioning route (England)
In timetable: -  
   
   
PBR Likely Healthcare Resource Group included.
   
Implications Available only to registered users