Staff Writer

A month after first revealing that lead RNAi drug ALN-RSV01 demonstrated statistically significant antiviral activity in a Phase II respiratory syncytial virus (RSV) trial, Alnylam Pharmaceuticals Inc. presented the detailed data.

The double-blind, placebo-controlled, 88-patient study met its primary efficacy endpoint of reducing RSV infection rate. Patients receiving ALN-RSV01 just before and after experimental RSV inoculation demonstrated a 38.1 percent reduction in infection rate as measured by plaque assay (p<0.01).

Even using the most conservative measures, the drug induced a statistically significant 23.5 percent reduction in infection rate, Vice President of Clinical Research Akshay Vaishnaw said during a conference call. He noted that 88.1 percent of placebo-treated patients became infected, compared to 67.4 percent of drug-treated patients. ALN-RSV01 also was well tolerated with no serious or severe adverse events.

Barry Greene, president and chief operating officer of Cambridge, Mass.-based Alnylam, heralded the data as a "historic event" and the "first-ever human proof of concept for an RNAi therapeutic."

Although Opko Health Inc. is in Phase III for wet age-related macular degeneration (wet-AMD) with the siRNA drug bevasiranib, the company's Phase II trial did not include a placebo arm. The ongoing Phase III trial is a randomized, double-blind, active-controlled 330-patient study and is expected to produce initial data in mid-2009. (See BioWorld Today, July 12, 2007.)

Allergan Inc. is conducting a randomized, double-blind, active-controlled Phase II trial with its wet-AMD siRNA drug AGN211745 (previously known as Sirna-027) but has not yet reported data.

Wall Street didn't appear to share Alnylam's enthusiasm: the company's shares (NASDAQ:ALNY) fell $1.52 to close at $28.40 Friday, and shares of other RNAi companies also traded relatively flat.

Mike King, analyst with Rodman & Renshaw LLC, said some folks may be worried about the lack of a significant difference in clinical symptoms between the treated and placebo groups in the trial - a concern which he said reflects a misunderstanding of the purpose of the study.

As Vaishnaw pointed out during the conference call, the study was designed to demonstrate an antiviral effect. Obtaining a clinical effect would require "a different type of trial" in which ALN-RSV01 is administered later during the course of infection, he said.

Additionally, King noted that the trial utilized an artificially induced infection that does not generate a profound clinical effect, making any difference "difficult to detect and of questionable relevance."

Next up for ALN-RSV01 is a Phase II trial in naturally infected adults, which is slated to begin in the first half of this year. Eventually, the drug could be used to treat RSV infection in both children and adults, Greene said, differentiating it from MedImmune Inc.'s blockbuster humanized monoclonal antibody Synagis (palivizumab), which is used to prevent infection in premature infants. Earlier this year, MedImmune (now a unit of AstraZeneca plc) submitted a biologics license application for its next-generation RSV antibody motavizumab, also for prevention of infection in high-risk infants.

Since RSV is a large market that necessitates a primary care sales force, Greene said Alnylam plans to partner ALN-RSV01. The company may even do a deal before beginning Phase III trials and has seen "significantly increased" interest due to today's data, he added. But Alnylam is in no rush - the company reported $455.6 million in cash, equivalents and marketable securities at the end of 2007 thanks to a host of partnerships with Roche Holding AG, Novartis AG, Medtronic Inc. and others.

In addition to ALN-RSV01, Alnylam's pipeline includes a number of preclinical RNAi programs. Most advanced are the systemic hypercholesterolemia drug ALN-PCS01 and the systemic liver cancer drug ALN-VSP01, one of which is expected to become the subject of an investigational new drug application filing before the end of the year. Greene said Alnylam also is working with partner Medtronic to advance a preclinical Huntington's disease program toward the clinic.