Alnylam Initiates Phase IIb Clinical Trial For RSV Infection

The Phase IIb trial is a multi-center, global, randomized, double-blind, placebo-controlled study in RSV-infected lung transplant patients with a primary endpoint of a reduction in 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), of greater than 80% of their pre-infection baseline value; and, improvement in RSV symptoms as measured by mean cumulative daily total symptom score.

The trial is expected to enroll 76 patients who will be randomized in a one to one, drug to placebo ratio. All patients will receive standard of care, and those receiving ALN-RSV01 will have drug administered as a 0.6mg/kg dose by inhalation using an investigational eFlow Nebulizer System (PARI Pharma) once daily for five days.

Results from previous pre-clinical and clinical studies with ALN-RSV01 have documented the drug’s safety profile and anti-viral activity. In 2009, Alnylam completed a Phase IIa study of ALN-RSV01 in RSV-infected adult lung transplant patients. In this small study of 24 patients, ALN-RSV01 was safe and well tolerated, which was the primary study objective.

Interpretation of secondary study objectives, including anti-viral activity, was confounded by certain imbalances, for example baseline viral loads, that occurred by chance. By day 14, there was a greater reduction in cumulative symptoms scores in the ALN-RSV01 group. At the 90 day endpoint, ALN-RSV01 treatment was associated with evidence for improved recovery of lung function and a statistically significant reduction in the incidence of new or progressive BOS.

In 2008, the anti-viral activity of ALN-RSV01 was demonstrated in the company’s Phase II GEMINI study, which was a randomized, double-blind, placebo-controlled study of intranasal ALN-RSV01 in 88 adult volunteers experimentally infected with RSV.

In this study, ALN-RSV01 treatment was associated with a decrease in the incidence of RSV infection as compared with placebo. Finally, pre-clinical studies have documented the anti-viral activity of ALN-RSV01 in rodent models (Alvarez et al., Antimicrob Agents Chemother. 53(9):3952-62, 2009).

The ALN-RSV program is partnered with Kyowa Hakko Kirin Co in Asia, and Cubist Pharmaceuticals worldwide except Asia. In parallel with Alnylam’s development of ALN-RSV01 for the treatment of RSV in lung transplant patients, Alnylam and Cubist are developing a second-generation compound, ALN-RSV02, which will be focused on the pediatric patient population.

Akshay Vaishnaw, senior vice president of clinical research at Alnylam, said: “RSV is a major infectious disease in both adult and pediatric populations and there are no effective treatments used widely today. It is an especially dangerous infection in immuno-suppressed patients, such as lung transplant patients.

“Alnylam’s new Phase IIb study aims to repeat and extend the results we saw in our previous Phase IIa study in the same patient population. In that small study, treatment with ALN-RSV01 fulfilled the primary study objective of safety and tolerability, and showed preliminary evidence for improved recovery of lung function and a statistically significant reduction in the incidence of new or progressive BOS.”