Top-line results from Alnylam’s ALN-RSV01 Phase IIb trial on RSV infection

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today top-line results from a Phase IIb trial with ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection in lung transplant patients. The primary endpoint of the study was the incidence of new or progressive bronchiolitis obliterans syndrome (BOS) at 180 days after RSV infection. The study missed the primary endpoint of reduced BOS in an "intent-to-treat" (ITTc) analysis of confirmed RSV infected patientslast observation carried forward" (LOCF) with a p-value of 0.028, and of ITTc patients treated "per protocol" (PP) with a p-value of 0.025. In all analyses, ALN-RSV01 treatment was associated with a clinically meaningful treatment effect, with a reduction of over 50% in the incidence of day 180 BOS as compared with placebo.

"We believe that these data provide important evidence that ALN-RSV01 reduces the incidence of new or progressive BOS in RSV-infected lung transplant patients, replicating the findings from our Phase IIa study of this agent in the same clinical setting. We plan to discuss the results of this study with U.S. and European regulatory authorities later this year and, thereafter, determine appropriate next steps, if any, on our ALN-RSV program," said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. "In the meanwhile, we continue to execute on our 'Alnylam 5x15' product strategy with a focus on our transthyretin-mediated amyloidosis and hemophilia programs."

The Phase IIb trial was an international multi-center, randomized, double-blind, placebo-controlled study of ALN-RSV01 in RSV-infected lung transplant patients. RSV infection in lung transplant patients represents a significant unmet medical need due to the risk of developing new or progressive BOS, an irreversible loss of function in the transplanted lung associated with approximately 50% mortality within five years. The primary endpoint of the Phase IIb trial was the incidence of new or progressive BOS at 180 days; these data were adjudicated by an independent panel of three transplant physicians who were blinded to study drug treatment assignment. The trial enrolled 87 patients who were randomized in a one-to-one, drug-to-placebo ratio; a total of 33 sites participated from six countries. Based on local study site diagnosis of RSV infection, a total of 45 patients were randomized to receive ALN-RSV01 and 42 patients were randomized to receive placebo, defining the overall intent-to-treat study cohort (ITT). Following central laboratory testing by PCR analysis, 10 patients could not be confirmed as infected for RSV; these patients happened to include nine patients randomized to receive placebo and one patient randomized to receive ALN-RSV01. Accordingly, a total of 77 patients (placebo,s practices.

Top-line results are detailed in the table below. In the ITTc analysis, ALN-RSV01 narrowly missed the primary endpoint of new or progressive BOS at 180 days. ALN-RSV01 treatment was associated with a statistically significant reduction in the incidence of day 180 BOS in the prospectively defined LOCF and PP analyses. In all analyses, treatment with ALN-RSV01, as compared with placebo, was associated with a clinically meaningful reduction in the incidence of BOS with a treatment effect ranging from approximately 54% to 65%. ALN-RSV01 was found to be generally safe and well tolerated in the study, with a comparable incidence of reported adverse events in placebo and study drug treatment arms. There were three deaths in the study, two in placebo and one in ALN-RSV01, all of which were determined to be unrelated to treatment. Additional study results are expected to be presented at the European Respiratory Society Annual Congress taking place September 1-5, 2012 in Vienna.