Antisense Therapeutics is pleased to advise that the Phase II clinical trial of ANP’s immunomodulatory therapy, ATL1102 for Duchenne Muscular Dystrophy (DMD) has met its primary endpoint confirming the safety and tolerability of ATL1102 for advancement into a potentially pivotal Phase IIb clinical trial.
Importantly, the final trial results have also confirmed the drug’s positive effects on the secondary trial endpoints that assessed the drug’s activity and efficacy including measuring the effects on immune cell numbers in the blood and measuring the participants’ functional capacity as evaluated via Performance of Upper Limb Test (PUL2.0), grip and pinch strength and distal mobility (using the MyoSet, MyoGrip, MyoPinch and MoviPlate tools, respectively).
Additionally, the Company is very pleased to report that MRI assessment of the upper limb muscles of the patients with DMD has also shown the drug’s apparent beneficial effects in stabilising the fat fraction percentage within the muscles of the forearm (increase in fat levels is another key marker of disease progression in non-ambulant DMD boys). The data shows a stabilisation in the percentage of fat in the forearm muscles and an increase/maintenance of functional muscle mass, which is both outstanding and unexpected for a drug treating the inflammation (and not the muscle dystrophin loss).
Results overview
The primary objective of the ATL1102 trial was to assess the safety and tolerability of 25 mg of ATL1102 administered once weekly (subcutaneous injection) for 24 weeks in nine non-ambulatory DMD participants. ATL1102 was assessed to be generally safe and well tolerated. No Serious Adverse Events were reported with no safety concerns expressed by the Data Safety Monitoring Board. There were no participant withdrawals from the study. The most commonly reported adverse events have related to the subcutaneous administration of the drug, mainly injection site erythema and skin discoloration which were generally regarded as mild and either resolved or were close to resolution at the end of the monitoring period. Overall, ATL1102 demonstrated an excellent safety profile in this trial.
Dr Ian Woodcock, Paediatric Neurologist and Honorary Fellow at The Murdoch Children’s Research Institute, Melbourne and the Principal Investigator of the ATL1102 Phase II DMD trial said, “the study met its primary endpoint showing ATL1102 to be safe and well tolerated with no serious adverse events being reported and no participant withdrawing from the study. With very few treatment options for boys with Duchennes who are no longer ambulant, it has been great to enable the boys to participate in this clinical trial and I am most encouraged by the outcomes of the study”.
ATL1102 is an inhibitor of CD49d expression on certain immune cells (e.g. T lymphocytes). It has been reported in research literature that patients with DMD who have a greater number of CD4+ and CD8+T lymphocytes with high levels of CD49d have more severe and rapid disease progression. ATL1102 is the only drug in clinical development for DMD targeting CD49d and one of a very limited number of treatments being tested in non-ambulant boys with DMD.
In assessing the effects of ATL1102 on immune cell numbers in the blood of participants, the immune cell data has shown a consistency in the mean reductions in the number of lymphocytes including T-lymphocytes (i.e. CD3+, CD3+CD4+, CD3+CD8+ and importantly, those expressing CD49d) measured from baseline to week 8, 12 and 24 (end of dosing) with a rebound of these markers to around starting levels post dosing at week 28. As previously reported, the mean number of CD3+CD49d+ T cells (i.e. mostly CD3+CD4+CD49d+ and CD3+CD8+CD49d+cells) at week 24 is statistically significantly lower vs week 28 (p=0.030 paired T test) suggesting the drug is working through its targeted mechanism of action. We further report that the mean number of NK lymphocytes (CD3-CD16+CD56+) and NK lymphocytes expressing CD49d+ at week 8,12 and 24 is statistically significantly lower vs baseline using a mixed model for repeated measurements (p=0.018), with comparable NK lymphocyte numbers at week 28. This data demonstrates the drug’s positive effects on modulating CD49d+ lymphocytes in the blood during treatment.
As reported in December 2019, the PUL2.0 data showed that 7 of the 9 participants demonstrated either increases or no change in their PUL2.0 scores from...
(All Rights Reserved)