Trial Supports ATL1102’s Safety in Improving Muscle Strength, Function in DMD Boys

A Phase 2 trial of ATL1102 met its primary goal of demonstrating favorable safety and tolerability in boys with Duchenne muscular dystrophy (DMD), final study results show.

ATL1102, developed by Antisense Therapeutics, was also effective at lowering the number of immune cells targeted by its mechanism of action, improving upper muscle strength and function, stabilizing the percentage of fatty tissue in muscles, and preserving muscle mass.

According to the company, these promising findings support advancing ATL1102 into a Phase 2b trial, an opinion that has been backed up by several international key opinion leaders in the field. Antisense has submitted an application to the European Medicines Agency requesting advice on this future trial in the European Union and U.K. Such advice is expected by mid-year.

In previous meetings, the European agency supported the study’s proposed safety and efficacy endpoints (goals), year-long duration, and use of higher doses.

“Our focus is to continue planning and to methodically and efficiently move our DMD program through Phase IIb in Europe,” Mark Diamond, CEO of Antisense Therapeutics, said in a press release.

“As we gain further certainty from the regulatory process on the parameters of the next trial, which may lead to early market approval, we will assess funding and trial management options and also engage in discussions with interested potential partners ahead of commencement of Phase IIb,” Diamond added.

ATL1102 is an antisense inhibitor of CD49d, a subunit of the Very Late Antigen-4 (VLA-4) receptor found on the surface of immune T-cells. By blocking this receptor, ATL1102 is expected to lower the number of T-cells producing high amounts of CD49d, which have been linked to rapid and severe DMD progression.

The safety, tolerability, preliminary efficacy, and activity of ATL1102 were investigated in a Phase 2 trial (ACTRN12618000970246) enrolling nine DMD boys, ages 10–18, all unable to walk without assistance.

The study’s main goal was to evaluate the safety and tolerability of ATL1102 given once weekly by subcutaneous (under-the-skin) injection at a dose of 25 mg for 24 weeks (six months). Secondary goals included assessing its effects on functional capacity, upper limb strength, and levels of immune cells in the blood.

Recent findings from the study showed that ATL1102 was safe and well-tolerated, and led to improvements in boys’ functional capacity (assessed by the Performance of Upper Limb Test, or PUL2.0) and upper limb strength — assessed by the MyoGrip and MyoPinch tests.

Updated findings continue to show favorable safety and tolerability. No serious adverse events or safety concerns were reported, and none of the boys withdrew from the study.

“The study met its primary endpoint showing ATL1102 to be safe and well tolerated,” said Ian Woodcock, MD, pediatric neurologist at the Murdoch Children’s Research Institute, and principal investigator of the trial.

“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,” Woodcock added.

Results reported last December have also shown that PUL2.0 scores either increased or remained stable in seven boys, suggesting an overall improvement in functional capacity.

The boys continue to show overall improvements and a tendency for disease stabilization across different measures of functional capacity and upper muscle strength.

ATL1102 had previously been found to lower the number of T-cells in the blood, including those producing large amounts of CD49d.

Updated results now show that in addition to T-cells, ATL1102 lowered the number of natural killer immune cells producing large amounts of CD49d, demonstrating the therapy’s strong activity at modulating the levels of CD49d-positive immune cells.

MRI data also showed a slight reduction in the percentage of fatty tissue in muscles, accompanied by maintenance or even an increase in the percentage of lean muscle mass, which suggests that ATL1102 may also increase functional muscle mass in DMD patients.

Additional analyses found a positive correlation between MRI data and muscle grip strength, as measured by the MyoGrip test.

Improvements in quality of life — assessed by questionnaires — were also seen across several domains following treatment, such as problems of daily activities and treatment management.

“The data certainly suggests an overall ‘stabilization’ in disease progression at the very least which of itself is a very positive clinical outcome,” said Thomas Voit, MD, PhD, director of the NIHR Great Ormond Street Hospital Biomedical Research Centre in the U.K.

“The consistency of positive clinically relevant effects of ATL1102 treatment across muscle measures of structure, strength and function are very pleasing and provide great encouragement for the treatment of non-ambulant patients with DMD,” Voit added.

In addition to the launch of a future Phase 2b trial of ATL1102 in DMD, Antisense is also planning to request orphan drug designation for the therapy in the U.S. and E.U.

In the meantime, the company is exploring ATL1102’s therapeutic potential for other muscular dystrophies and neurological conditions that are poorly controlled by conventional anti-inflammatory medications.