Results Reported in Phase II Clinical Trial of Oral Firategrast for Relapsing MS
February 27, 2012
In a phase II trial of an oral compound called firategrast (Glaxo Smith Kline) involving 343 people with relapsing-remitting MS, the highest doses suggested benefit by reducing MRI-detected disease activity compared to placebo. Dr. David Miller (University College London Institute of Neurology) and colleagues report their findings in Lancet Neurology (2012; 11: 131–39). Results were originally presented at the 2010 meeting of the European Committee of Treatment and Research in MS. The study was funded by GlaxoSmithKline.
Background: Multiple sclerosis involves immune system attacks on the brain and spinal cord. Similar in approach to the approved infused therapy natalizumab (Tysabri®, Biogen Idec and Elan), oral firategrast interferes with movement of immune cells from the bloodstream into the central nervous system by blocking the molecule known as alpha 4-integrin.
The Study: Participants were randomly assigned to receive 150 mg, 600 mg, 900 mg or 1200 mg of firategrast or inactive placebo for 6 months. The primary outcome measure was the cumulative number of active (“enhancing”) new MS brain lesions (areas of tissue damage), detected with MRI scans. Secondary outcomes included relapse rate.
The two highest doses caused a significant decrease (49%) in the average rate of new lesions compared with the placebo group. No significant differences in relapse rate were observed between the firategrast groups and the placebo group. After discontinuation of the study treatment, participants were observed for 12 weeks, and disease activity in all firategrast groups returned to levels similar to the placebo group.
Urinary tract infections were reported more often in the two high dose groups, and resolved without requiring discontinuation of treatment. Some increases in liver enzymes were observed, and these reversed after discontinuation of the study drug. No cases of PML (progressive multifocal leukoencephalopathy, a severe brain infection) occurred in this study. PML has emerged in some people who have taken natalizumab.
Comment: This study was a 6 month, phase II trial of an experimental oral therapy with similarities to natalizumab, an approved therapy given by monthly infusions. The results suggest that firategrast may reduce some signs of disease activity with no serious adverse events. However, it will be important to observe the occurrence of urinary tract infections (which did not occur in natalizumab studies) and to monitor for PML or other infections in longer, larger trials which are needed to determine firategrast’s safety and effectiveness for treating MS.