Date: 2015-03-15
Type of information: Presentation of results at a congress
phase: presentation of results at a meeting with members of the Association of Black Cardiologists (ABC)
Announcement: results
Company: Alnylam Pharmaceuticals (USA - MA)
Product:
Action mechanism:
Disease: transthyretin (TTR)-mediated amyloidosis (ATTR amyloidosis) patients with familial amyloidotic cardiomyopathy (FAC)
Therapeutic area: Genetic diseases - Rare diseases
Country:
Trial details:
Latest
news: * On March 15, 2015, Alnylam Pharmaceuticals, a leading RNAi therapeutics company, announced results from a retrospective natural history study evaluating disease progression in transthyretin (TTR)-mediated amyloidosis (ATTR amyloidosis) patients with familial amyloidotic cardiomyopathy (FAC). Amongst other findings, study results showed a mean decline of 140 meters in 6-minute walk distance (6-MWD) over an 18-month period in FAC patients with mild-to-moderate heart failure. These natural history findings support the company\'s co-primary endpoint for its Phase 3 ENDEAVOUR clinical study with revusiran. Findings from the natural history study were presented at a meeting with members of the Association of Black Cardiologists (ABC). This study was performed to characterize disease severity and rate of progression in a multinational population of FAC patients. Demographics and time from first visit to death were collected retrospectively on 137 FAC patients from two countries at two large amyloidosis centers: The National Amyloidosis Centre (NAC) in London (N=88); and Columbia University in New York (N=49). The majority of patients had mild-to-moderate heart failure (40% NYHA class II, 43% NYHA class III) and the V122I TTR mutation (85%), with a median age of 72 years. Serial 6-MWD data were collected retrospectively in 39 patients followed at NAC, while hospitalizations were captured in the 49 patients followed at Columbia. Median survival was 34.1 months for the pooled group of 137 patients, and median time to first cardiovascular hospitalization was 26.7 months. There was a clear decline in 6-MWD over 18 months. Specifically, at 12 and 18 months, the mean decline in 6-MWD was 106 +/- 24 meters and 140 +/- 39 meters, respectively. These results are consistent with the 91 meter and 118 meter decline compared to baseline at 12 and 18 months, respectively, observed in 10 FAC patients in the published TRACS study (Ruberg et al., Am Heart J 2012). There was no consistent change over time in NT-proBNP levels among 78 patients from the NAC with data available for analysis. Based on these findings, Alnylam believes that the ongoing Phase 3 ENDEAVOUR trial of revusiran in FAC patients has the potential to show an impact of TTR lowering on the co-primary endpoint of decline from baseline in 6-MWD at 18 months. In addition, Alnylam has assembled natural history data from academic collaborators on approximately 250 patients with SSA and plans to present those findings at a future meeting. In January 2014, Alnylam and Genzyme, a Sanofi company, formed an alliance to accelerate and expand the development and commercialization of RNAi therapeutics across the world. The alliance is structured as a multi-product geographic alliance in the field of rare diseases. In the case of revusiran, Alnylam and Genzyme are co-developing and co-commercializing the investigational RNAi therapeutic in North America and Western Europe, while Genzyme is developing and commercializing revusiran in the rest of world.
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