Alnylam Pharmaceuticals publishes ALN-RSV01 Phase IIa study results

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company announced today that it has published results in the American Journal of Respiratory and Critical Care Medicine (Zamora et al., Am. J. Respir. Crit. Care Med., doi:10.1164/rccm.201003-0422OC, 2010) from its double-blind, placebo-controlled, randomized Phase IIa study of ALN-RSV01 in lung transplant patients naturally infected with respiratory syncytial virus (RSV). These data, presented previously at the BIT Life Science's 2^nd Annual Summit of Antivirals held in Beijing, China in July 2009, documented for the first time safety and tolerability of inhaled ALN-RSV01 in a naturally infected patient population. The results also demonstrated statistically significant improvements in clinical symptom scores and reductions in the incidence of bronchiolitis obliterans syndrome (BOS), an irreversible and life-threatening complication of RSV infection in lung transplant patients resulting in approximately 50% mortality within three to five years of onset.

“We are also pleased with the continued and growing track record of Alnylam publications regarding our clinical trial results, as these importantly demonstrate our translation of RNAi therapeutics to patients.”

"Our Phase IIa study of ALN-RSV01 demonstrated safety and tolerability in a naturally infected patient population. The study also demonstrated statistically significant effects on certain clinical endpoints that warrant verification in a larger study such as our current Phase IIb study which is actively enrolling," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President of Clinical Research. "We are also pleased with the continued and growing track record of Alnylam publications regarding our clinical trial results, as these importantly demonstrate our translation of RNAi therapeutics to patients."

The Phase IIa study was conducted at 11 sites in four countries, where 24 lung transplant patients with confirmed RSV infection were randomized to receive inhaled ALN-RSV01 or placebo once daily for three consecutive days. Overall, the study achieved its primary objective of demonstrating safety and tolerability of ALN-RSV01. Interpretation of anti-viral effects for ALN-RSV01 was confounded by an imbalance in certain baseline patient characteristics. There was a statistically significant improvement in clinical symptom scores in patients receiving ALN-RSV01. Further, although the study was not powered for efficacy due to the small sample size, data at 90 days showed preliminary evidence for improved recovery of lung function and a statistically significant reduction in the incidence of new or progressive BOS, as compared with placebo>

"RSV infection in lung transplant patients is a cause of significant morbidity and even mortality due to the potential for both acute and chronic lung rejection," said Martin Zamora, M.D., Professor of Medicine, and Medical Director, Lung Transplant Program, University of Colorado Health Sciences Center, and Principal Investigator for the trial in the U.S. "The results from this Phase IIa study with ALN-RSV01 are encouraging and support the continued development of an RNAi therapeutic for the treatment of RSV infection, a major unmet medical need with no effective treatments. I am pleased to be involved in the ongoing Phase IIb in the adult lung transplant patient population and look forward to continuing enrollment in this trial."

As a result of this study, Alnylam initiated earlier this year a multi-center, global, randomized, double blind, placebo-controlled Phase IIb trial for ALN-RSV01 in RSV-infected adult lung transplant patients. This new study aims to repeat and extend the results of the Phase IIa study. The primary endpoint is the incidence of new or progressive BOS. Secondary endpoints include assessments for safety and additional measurements of efficacy, including: anti-viral activity; recovery of lung function, as monitored by the proportion of patients with forced expiratory volume in the first second (FEV1); and, improvement in RSV symptoms as measured by mean cumulative daily total symptom score. The Phase IIb study is expected to enroll up to 76 patients.