Preliminary results from a CD49d antisense drug ATL1102 6 month Phase II trial in non-ambulant patients with Duchenne’s Muscular Dystrophy


Ultra-Rare myopathies and dystrophies (<1:100,000 worldwide)

Poster Number: 202


Nuket Desem, George Tachas, Ian Woodcock, Monique Ryan


1. Antisense Therapeutics Limited, 2. Antisense

The safety and activity of ATL1102, an antisense drug to the RNA for CD49d, the alpha subunit of VLA-4 1, is being evaluated in a 24 week dosing study in non-ambulant patients with Duchenne’s Muscular Dystrophy (DMD). DMD is an X linked inherited disease caused by mutations in the dystrophin gene resulting in muscle breakdown from contraction, and immune mediated inflammatory damage, leading to loss of ambulation, upper limb function and respiratory and cardiac failure. DMD immune mediated inflammatory damage is currently treated with corticosteroids but there is a need for safer and more effective treatments. Patients with DMD who have a greater number of immune T cells with high levels of CD49d expression have more severe and rapid disease progression despite corticosteroid use2. ATL1102 was previously shown to reduce disease activity in a Phase II multiple sclerosis study1.
In a single centre, open label Phase II study, nine adolescent non-ambulatory DMD male patients (10-18 years) are being treated with 25mg of ATL1102 subcutaneously injected once weekly for 24 weeks and monitored for a further 8 weeks. The primary study endpoints relate to safety and tolerability with secondary endpoints to assess the drug activity via effects on white blood cells and on disease progression via muscle strength and functional analysis (ACTRN12618000970246) 3. A review was undertaken of the preliminary data from the first 6 patients who had completed their 24 weeks of dosing.
The preliminary data review suggested a positive drug effect of ATL1102 at the dose tested both at immunomodulatory (i.e. effects on relevant immune cells) and disease progression (i.e. effects on muscle strength) levels. With respect to the safety related trial data, no Serious Adverse Events (SAE’s) had been reported to date. The Data Safety Monitoring Board had evaluated the safety data at that time and recommended continuation of the trial with no safety concerns. The number of immune T cells expressing CD49d, were trending downward during the 24 week treatment phase while returning to around starting levels post dosing. As an indicator of ATL1102’s suggestive effects on disease progression the patients pinch and grip strength as assessed by the Myo-Pinch and Myo-Grip device increased from baseline by a mean +0.1 kg 95% CI [-0.23, 0.34] and +0.3 kg 95% CI [-0.38, 1.08] respectively. This is compared to losses in muscle pinch and grip strength of -0.38kg 95% CI [-0.53, -0.22] and -0.5 kg [-1.01, 0.002] respectively reported in a study in 9 non-ambulant DMD patients on corticosteroids assessed at 6 months4.
In an ongoing study of ATL1102 in patients with DMD treated for 24 weeks, no SAE’s have been reported while preliminary trial data from the first 6 patients having completed their dosing is suggestive of a drug effect of ATL1102 on the CD49d+ T cell numbers and the upper limb muscle grip and pinch strength.

1 Limmroth et al (2014). Neurology, 11:83 (20)’ 1780-8
2 Pinto Mariz et al (2015). Skeletal Muscle; 5: 45-55.
4 Ricotti et al (2016). PLos One, 11(9) e0162542

Key Words.
Antisense and ATL1102
VLA-4 and CD49d
Duchenne’s Muscular Dystrophy and Non-Ambulant