ABSTRACT
Objective: This study evaluated the efficacy and safety of ATL1102, an antisense oligonucleotide that selectively targets the RNA for human CD49d, the α subunit of very late antigen 4, in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods: In a multicenter, double-blind, placebo-controlled randomized phase II trial, 77 patients with RRMS were treated with 200 mg of ATL1102 subcutaneously injected 3 times in the first week and twice weekly for 7 weeks or placebo and monitored for a further 8 weeks. MRI scans were taken at baseline and weeks 4, 8, 12, and 16. The primary endpoint was the cumulative number of new active lesions (either new gadolinium-enhancing T1 lesions or nonenhancing new or enlarging T2 lesions) at weeks 4, 8, and 12.
Results: A total of 72 patients completed the study and 74 intention-to-treat patients were assessed. ATL1102 significantly reduced the cumulative number of new active lesions by 54.4% compared to placebo (mean 3.0 [SD 6.12] vs 6.2 [9.89], p = 0.01). The cumulative number of new gadolinium-enhancing T1 lesions was reduced by 67.9% compared to placebo (p = 0.002). Treatment-emergent adverse events included mild to moderate injection site erythema and decrease in platelet counts that returned to within the normal range after dosing.
Conclusions: In patients with RRMS, ATL1102 significantly reduced disease activity after 8 weeks of treatment and was generally well-tolerated. This trial provides evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders.
Classification: This study provides Class I evidence that for patients with RRMS, the antisense oligonucleotide ATL1102 reduces the number of new active head MRI lesions.
Via Krishan Maggon
Primary efficacy endpoint met with a statistically significant reduction of sIGF-I
levels of 26% at the 400mg/week dose (P<0.0001; highly significant)
• 36% average reduction in sIGF-I for lower body weight patients
• Positioned to move into Phase III stage of development
• Safe and well tolerated with no serious adverse events related to dosing reported
CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MSVolker Limmroth, MD, Frederik Barkhof, MD, PhD, Nuket Desem, MBA, Mark P. Diamond, MBA, George Tachas, PhD; For the ATL1102 Study Group
Correspondence to Dr. Tachas: george.tachas@antisense.com.auPublished online before print September 19, 2014, doi: 10.1212/WNL.0000000000000926Neurology 10.1212/WNL.0000000000000926