Antisense Therapeutics (ASX: ANP) has reported that a post hoc analysis of brain lesion data from the Phase II study of the ATL1102 in patients with multiple sclerosis (MS) [Limmroth et al 2014 Neurology] has shown that ATL1102 significantly reduces the number of active MS lesions that convert to “Black Holes”, areas of axonal (nerve fiber) loss or permanent tissue damage.
The positive effect of ATL1102 on black holes suggests that along with its action in reducing the number of inflammatory lesions, ATL1102 may also be potentially neuroprotective in protecting the axons in the lesion from degeneration.
ATL1102 is an antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4). In a Phase II study of ATL1102 in RRMS patients, ATL1102 met its primary endpoint in reducing the cumulative number of new active MS lesions by 54% vs placebo.
A post hoc analysis of the Magnetic Resonance Imaging data from the Phase II study was conducted to assess the effect of ATL1102 on the conversion of the remaining active lesions to T1 black holes (BH). The analysis showed that there was a significant reduction in active lesions at weeks 8 and 12 converting to BH at week 16 in the ATL1102 treated patients (13.2%) compared to patients on placebo (27.6%), with the odds of converting to BH in the placebo arm 2.51 times the odds of converting in the treatment arm (p= 0.0376).
An inhouse review of published data on the effect of registered MS disease modifying agents on BH2-5 suggests the effects observed with ATL1102 in reducing active lesions converting to BH appear relatively rapid (seen with only 8 weeks of dosing) and potent.
The post hoc analysis was conducted by Dr Frederik Barkhof, Professor of Neuroradiology, Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, and co-author on the Limmroth et al Neurology publication.
Prof Barkhof said of the results:
“Assessing the effect of MS treatments to prevent lesions evolving into so-called “Black Holes” is a relatively new manner to determine neuroprotection in MS. Reducing black holes signifies preservation of brain tissue and the slowing of MS disease progression. The positive effects observed with ATL1102 on black holes are encouraging and suggestive of ATL1102’s potential neuroprotective effects, which could be very important, particularly when contemplating the drug’s potential as a treatment for progressive forms of MS.”
Antisense Therapeutics has filed a provisional patent application incorporating this new data while an abstract of the results is to be submitted for presentation at an MS scientific meeting this year.