Multiple sclerosis: ATL1102, an antisense inhibitor of CD49d, reduces by 54.4% the cumulative number of new active brain lesions


Phase IIa clinical trial data on ATL1102 were published in the medical journal Neurology. The article highlights the successful outcomes of the randomised, double-blind, placebo-controlled study in 77 patients with relapsing-remitting multiple sclerosis ( RRMS ). ATL1102 met its primary end point after only two months of dosing, showing a significant reduction, by 54.4% ( p=0.01 ) in the cumulative number of new active brain lesions in patients taking ATL1102 compared to placebo.

The efficacy outcomes from this study were viewed to be as good as, or superior to, those achieved with drug Tysabri ( Natalizumab ) at a similar stage in its clinical development.
Tysabri is a monoclonal antibody drug targeting the VLA-4 receptor ( same target as ATL1102 ); it is regarded as the current efficacy benchmark for the treatment of RRMS.

The ATL1102 phase IIa trial has provided evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders such as multiple sclerosis.
ATL1102 was shown to be highly effective in reducing brain lesions in RRMS patients with a quick onset of action and a clinical safety profile that strongly supports its ongoing development as a treatment for this disease.

ATL1102 is a second generation antisense inhibitor of CD49d, a subunit of VLA-4 ( Very Late Antigen-4 ). In inflammation, white blood cells ( leukocytes ) move out of the bloodstream into the inflamed tissue, for example, the central nervous system ( CNS ) in multiple sclerosis, and the lung airways in asthma.
The inhibition of VLA-4 may prevent white blood cells from entering sites of inflammation, thereby slowing progression of the disease. VLA-4 is a clinically validated target in the treatment of multiple sclerosis.
Antisense inhibition of VLA-4 has demonstrated positive effects in a number of animal models of inflammatory disease.

ATL1102 was previously shown to be highly effective in reducing multiple sclerosis lesions in a phase II clinical trial in RRMS patients with the primary study results reported in 2008. The efficacy outcomes from this study were viewed to be as good as, or superior to, those achieved with Natalizumab.
Natalizumab can cause a potential lethal viral brain infection known as progressive multi focal leukoencephalopathy ( PML ).

Following the successful phase IIa trial, ATL1102 was then tested, amongst several other animal safety studies, in a chronic primate toxicology study. An unexpected adverse finding was noted in that study. ANP subsequently completed a new chronic primate toxicology to support a potential Phase IIb clinical trial. ( Xagena )

Source: Antisense Therapeutics, 2014

XagenaMedicine_2014



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