By Thomas S. May
CHICAGO -- September 30, 2015 -- Ozanezumab, a monoclonal antibody, has demonstrated disappointing efficacy results against the neurite outgrowth inhibitor protein Nogo-A in patients with amyotrophic lateral sclerosis (ALS), according to results of a phase 2 study presented at the 140th Annual Meeting of the American Neurological Association (ANA).
“The results of the study highlight the challenges in developing medicines for ALS, which include a limited understanding of mechanisms of the disease, limitations of pre-clinical models, and a lack of validated biomarkers,” explained Arseniy Lavrov, MD, GlaxoSmithKline, Stockley Park, United Kingdom, who presented the study during a scientific poster session on September 28.
The phase 2 study included 303 patients with ALS who were randomised to receive ozanezumab (n = 152) or placebo (n = 151) over 48 weeks.
Primary endpoints were joint rank analysis of function (ALS Functional Rating Scale-Revised) and survival. Secondary endpoints included respiratory function, muscle power, and survival. Health outcomes, safety, immunogenicity, and pharmacokinetics were also assessed.
Analysis of the results indicated a non-significant difference in the joint rank score in favour of placebo (difference -30, P =.120), and all secondary efficacy endpoints supported this finding.
There was no apparent imbalance between treatment groups in adverse events, haematology, chemistry, vital signs, or electrocardiogram data. A numerically higher incidence of fatal serious adverse events, driven mainly by respiratory-failure events, was observed in those receiving ozanezumab compared with those receiving placebo.
According to Dr. Lavrov, the results indicate that Nogo-A may not be a viable therapeutic target for ALS. “The fact that the results of pre-clinical work did not translate into the clinical outcomes was unexpected and disappointing,” he noted.
Nogo-A has been considered a possible therapeutic target for ALS, since it has demonstrated a positive effect in animal models, and was well tolerated in a phase 1 clinical trial.
Funding for this study was provided by GlaxoSmithKline, Middlesex, United Kingdom.
[Presentation title: A Phase II Study of Ozanezumab in Amyotrophic Lateral Sclerosis. Abstract M761WIP]
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