ATL1102, Investigational Therapy for Duchenne Muscular Dystrophy, Approved for Phase 2 Trial

A Phase 2 clinical trial of ATL1102, Antisense Therapeutics’ investigational therapy for Duchenne muscular dystrophy (DMD), recently received authorization to proceed from the Royal Children’s Hospital (RCH), Melbourne Human Research Ethics Committee.

ATL1102 inhibits the protein CD49d, which is required for the normal function of the VLA-4 (very late antigen-4) receptor that sits on the surface of lymphocytes (a specific class of immune cells). In inflammation, white blood cells (lymphocytes) move out of the bloodstream into the inflamed tissue. Inhibiting VLA-4 may prevent white blood cells from entering inflamed sites, thereby slowing the progression of the disease.

The trial, which will be conducted at the RCH neuromuscular center in Australia, will investigate the effects of a single, weekly 25-mg dose of ATL1102 in wheelchair-bound boys with DMD, between 10 and 18 years old and weighing 25 to 60 kilograms (55 to 132 pounds).

The primary goal of the study is to determine the safety and tolerability of the single ATL1102 dose in these patients. Effectiveness will be evaluated by measuring inflammation levels and muscle damage markers.

Treatment will be given for six months, which may allow ATL1102 to show improvements in key clinical endpoints relevant to DMD progression, such as upper limb function.

Researchers expect to start the trial in the second quarter of 2018.

“Duchenne Muscular Dystrophy is a common, debilitating and ultimately terminal degenerative condition causing muscle inflammation and wasting,” Ian Woodcock, MD, one of the study’s principal investigators, said in a press release.

“There is a dire need for more effective therapies than those we have already. The approach of using ATL1102 to inhibit CD49d T cells to treat this inflammation is consistent with observations of international researchers and published studies,” he said. “Every day I see the pain and suffering that patients with DMD and their families go through and I am highly motivated to help in the development of new drugs and therapies that will benefit these children.”

An advisory board made up of international experts will oversee the study. This includes the inventors of Sarepta Therapeutics’ antisense drug, Exondys 51 (eteplirsen), approved by the U.S. Food and Drug Administration (FDA) to increase muscle dystrophin in DMD patients.

In 2016, Exondys 51 became the first exon-skipping treatment for DMD to obtain FDA approval. Sarepta designed the drug to correct the genetic defect underlying the disease, which would then restore the levels of dystrophin protein missing in muscles.

Despite showing promise in clinical studies, results were mixed, with some patients responding well and others not so well. A possible explanation was its rapid clearance from the blood — within hours.

Patients with immune T-cells expressing high levels of CD49d have been found to suffer from more severe disease and are usually wheelchair-bound by 10 years old.

Corticosteroids — the first-line treatment strategy for the management of inflammation associated with DMD — have so far provided insufficient evidence of their effectiveness, and are associated with significant side effects.

“We are very pleased to have received approval for our Phase II study in DMD patients. DMD is a rare disease with high unmet medical need, and so we are keen to establish ATL1102’s effectiveness in treating children with this devastating condition,” said Mark Diamond, CEO of Antisense Therapeutics.

ATL1102 is also being advanced in clinical trials for the treatment of multiple sclerosis.