Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi
therapeutics company, announced today that it has initiated a Phase IIb
trial in adult lung transplant patients with ALN-RSV01, an RNAi
therapeutic for the treatment of respiratory syncytial virus (RSV)
infection. RSV infection in lung transplant patients represents an
important unmet medical need; the condition is associated with
significant morbidity, including the development of acute lung
transplant rejection in 10% to 20% of infected patients. Lung transplant
patients infected with RSV are also at risk for an increase in frequency
of new or progressive bronchiolitis obliterans syndrome (BOS), a
life-threatening complication representing an irreversible disease of
the transplanted lung resulting in approximately 50% mortality within
three to five years of onset.
“RSV infection represents a significant risk for lung transplant
patients, and pulmonologists are clearly in need of an effective RSV
therapy in this critical disease area. Morbidities associated with RSV
infection in this setting are significant due to the potential for acute
and chronic lung rejection and other complications”
“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,” said Akshay Vaishnaw, M.D., Ph.D., Senior
Vice President, Clinical Research at Alnylam. “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.”
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 0.6 mg/kg
dose by inhalation using an investigational eFlow Nebulizer System (PARI
Pharma) once daily for five days.
“RSV infection represents a significant risk for lung transplant
patients, and pulmonologists are clearly in need of an effective RSV
therapy in this critical disease area. Morbidities associated with RSV
infection in this setting are significant due to the potential for acute
and chronic lung rejection and other complications,” said Professor
Allan R. Glanville, Director of Thoracic Medicine and Medical Director
Lung Transplantation, St. Vincent’s Hospital, Sydney. “I am encouraged
by the potential for ALN-RSV01 to treat RSV infection, and I look
forward to working with Alnylam in developing this RNAi therapeutic for
the treatment of RSV infection in lung transplant patients.”
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 statistically significant 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., Ltd. in
Asia, and Cubist Pharmaceuticals, Inc. 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. Cubist will take the lead in advancing
ALN-RSV02 in the pediatric setting in continued collaboration and 50-50
funding with Alnylam, and Cubist retains an opt-in right for ALN-RSV01
in the adult transplant indication.
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