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New Drugs Online Report for bucindolol
Information
Generic Name:
bucindolol 
Trade Name: Gencaro 
Entry Type: Licence extension  
 
Developmental Status
UK: None 
EU: None 
US: Phase III Clinical Trials 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Nov 09: Company intend to submit PIII study design to FDA 4Q 09 [1]. 
07/12/2009 13:44:35
Nov 09: granted fast track status in US [1]. 
07/12/2009 13:40:48
 
Trial or other data
May 10: ARCA has reached agreement with the FDA regarding a SPA on the design of a PIII study. It will be an international, multi-center, randomized, double-blind trial with a planned enrollment of 3,200 patients with chronic heart failure who have the genotype that appears to respond most favourably to bucindolol. This genotype is defined as the homozygous state for arginine (Arg/Arg) at amino acid position 389 of the beta-1 adrenergic receptor. The trial protocol includes a superiority comparison of bucindolol vs metoprolol CR/XL, which is approved for heart failure but has not been shown to exhibit any differentiation of clinical effects in heart failure patients with the beta-1 389 Arg/Arg genotype as compared to the Gly genotypes. The primary endpoint is a composite of cardiovascular mortality and cardiovascular hospitalization. The trial protocol includes two interim data analyses at pre-specified numbers of primary endpoints. If the results of either of the interim analyses meet the pre-specified criteria, ARCA would be able to formally submit a complete response to the FDA´s May 2009 Complete Response Letter and the results of the interim analysis could serve as the clinical effectiveness basis for FDA approval. The first interim data analysis is planned at 630 primary endpoints (57% of the projected total number). The trial protocol estimates reaching the first interim analysis 24-30 months into the trial. The SPA-defined criteria for fulfilling the FDA´s request for additional evidence of effectiveness include a hazard ratio 95% confidence interval upper bound of <0.999 (a p-value of approximately 0.050) and safety comparable to metoprolol CR/XL. Even with a positive outcome at either of the interim analyses, the planned trial is designed to proceed to conclusion, estimated to take a total of 3.5 years. The trial may start 2H 2011 provided the company can find the funding [3]. 
23/05/2010 22:25:25
Mar 10: Arca and the FDA have still not agreed a Special Protocol Assessment for a proposed PIII study of bucindolol. The company has had to submit revisions to the design of the study, which will now enroll 3,200 heart failure patients (increased from 3,000 patients previously) [2]. 
29/03/2010 21:56:50
Jan 10: BEST study published in Circulation: Heart Failure. 2010;3:21-28 
25/01/2010 10:40:34
Nov 09: The Company intends to submit a study protocol for review under the FDA’s Special Protocol Assessment process for the design of a trial to assess the safety and efficacy of Gencaro in 3,000 patients with chronic heart failure who have the genotype that appears to respond most favorably to Gencaro. It is anticipated that the study will evaluate superiority vs metoprolol CR/XL with a composite primary endpoint of cardiovascular mortality and cardiovascular hospitalization. Subject to agreement, the proposed trial could start in Q410 or 1H 11, with the required number of endpoints obtained within 2 years [1]. 
07/12/2009 13:56:46
The PIII BEST heart failure mortality study in over 2,700 patients included a DNA bank of over 1,000 patients, which was used to evaluate the effect of genetic variation on patients’ response to bucindolol. In this study, bucindolol appeared to produce enhanced clinical outcomes in the 47% of patients who were homozygous for the amino acid position 389 arginine polymorphism of the beta-1 adrenergic receptor. Further, an additional genetic variant, a deletion/insertion polymorphism of the alpha-2C adrenergic receptor has also been identified that may also influence patient responses to bucindolol. Subject to approval by the FDA, ARCA’s collaborator, Laboratory Corporation of America anticipates introducing a test for these genetic markers concurrent with the potential market launch of bucindolol, potentially making bucindolol the first genetically-personalized cardiovascular drug [1]. 
07/12/2009 13:56:34
   
References  
Available only to registered users
Category
BNF Category:
Beta-adrenoceptor blocking drugs (02.04)
Pharmacology: beta-blocker and mild vasodilator  
Epidemiology:  
Indication: Heart failure 
Additional Details:  
 
Method(s) of Administration
Oral 
 
Company Information
Name: Not Known 
US Name: ARCA 
 
NICE Information
Anticipated Commissioning route (England)
In timetable: -