Alnylam Announces Encouraging Exploratory Cardiac Endpoint Data For Patisiran in hATTR Amyloidosis

September 14, 2018
  • In post-hoc analysis, the exposure-adjusted rates of all-cause death and/or hospitalization were reduced approximately 50% in patients receiving Patisiran vs placebo
  • hATTR amyloidosis affects approximately 50,000 people worldwide


Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today publication of data from exploratory cardiac assessments in the APOLLO Phase 3 study of patisiran, an RNAi therapeutic for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The results were published online today in the journal Circulation, and showed that patisiran improved markers of cardiomyopathy in patients with hATTR amyloidosis with polyneuropathy.

“We are encouraged by these data from the APOLLO study on the effects of patisiran on measures of cardiac disease in hATTR amyloidosis patients with polyneuropathy,” said Pushkal Garg, M.D., Chief Medical Officer at Alnylam. “These data support the hypothesis that patisiran may favorably impact certain cardiac manifestations of hATTR amyloidosis. Accordingly, we believe these results support further study of the effects of patisiran on cardiac features of hATTR amyloidosis.”

The publication presents data on the treatment effects of patisiran relative to placebo on certain measures of cardiac structure and function in patients with echocardiographic evidence of cardiac amyloid involvement at study entry with no confounding medical history (APOLLO cardiac subpopulation*: n=126; 56 percent of total study population). In pre-specified analyses, left ventricular (LV) wall thickness was reduced by a mean of 0.9 mm (p=0.017) in patisiran-treated patients, compared to those receiving placebo. Global longitudinal strain was also significantly improved by an absolute value of -1.4 percent (p=0.015), suggesting improved systolic, or contractile, function. Differences in global longitudinal strain of this magnitude have been shown in other studies to be an independent predictor of survival in patients with ATTR and light-chain (AL) amyloidosis.1 In addition to the favorable impact on echocardiographic measures of cardiac structure and function, a treatment effect on NT-proBNP – a cardiac biomarker released in response to ventricular wall stress – was also observed in the cardiac subpopulation, with a significant 55 percent relative reduction in NT-proBNP levels compared to placebo. This effect was noted as early as 9 months of treatment, the first assessment time point in APOLLO. In post-hoc categorical analyses, a greater proportion of patients treated with patisiran versus placebo experienced reductions in LV wall thickness, decreases in global longitudinal strain and reductions in NT-proBNP relative to baseline, providing evidence for potential improvement in markers of cardiomyopathy.

In the overall study population, the proportions of patients with cardiac adverse events (AEs) and cardiac serious AEs (SAEs) were similar in the patisiran and placebo groups. The incidence of cardiac arrhythmia AEs was lower in the patisiran group compared with placebo (18.9 versus 28.6 percent). Deaths occurred in 4.7 percent of patients treated with patisiran (3.2 per 100 patient-years) and 7.8 percent of patients treated with placebo (6.2 per 100 patient-years). In a post-hoc analysis, the exposure-adjusted rates of all-cause death and/or hospitalization were 71.8 and 34.7 per 100 patient-years in the placebo and patisiran groups, respectively, representing an approximately 50 percent reduction in event rate. A similar trend was seen for reduction of all-cause death and/or cardiac hospitalizations.

hATTR amyloidosis affects approximately 50,000 people worldwide. The disease can affect multiple parts of the body, including the nervous (nerve), cardiac (heart), and gastrointestinal (digestive) systems.



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