Positive Early Results Support Continuation of Phase 2 Trial of ATL1102 for DMD

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by Alice Melão |

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Experimental therapy ATL1102 improved upper limb strength and function in six boys with Duchenne muscular dystrophy (DMD) unable to walk, according to early results of an ongoing Phase 2 clinical trial.

These results also indicate that the therapy has been well-tolerated with no safety concerns reported so far. Based on this positive safety profile, an independent monitoring board has recommended the continuation of the trial (ACTRN12618000970246).

The most recent data concerning the trial will be presented at the Action Duchenne International Conference, taking place Nov. 15–16 in Hinckley, U.K.

Developed by Antisense Therapeutics, ATL1102 is an antisense inhibitor of CD49d expression, a protein subunit of the VLA-4 receptor found on the surface of immune T-cells. In inflammation, these cells can migrate out of the blood stream into inflamed tissue. Antisense therapies contain non-coding (do not make proteins) messenger RNA, generated from DNA in protein production.

Previous studies suggested that DMD patients with a greater number of T-cells containing high levels of CD49d experience more muscle damage mediated by inflammation, as well as less ability to walk. By blocking CD49d, ATL1102 may prevent T-cell migration, resulting in lower inflammation and slower DMD progression.

The therapy candidate was designed as a potential alternative to corticosteroids, which are associated with serious side effects when used for a long period of time, as required for DMD treatment.

The Phase 2 trial recruited nine boys with DMD ages 10–18 at the neuromuscular center of the Royal Children’s Hospital Melbourne in Australia. All were unable to walk independently.

Treatment with 25 mg of ATL1102 is given weekly via subcutaneous (under-the-skin) injections for 24 weeks (six months).

Results from the first six patients showed that ATL1102 was well-tolerated and safe — the trial’s primary goal — with no serious adverse events being reported. The company expects this positive safety profile to support a longer dosing period of ATL1102 in a future Phase 2b trial.

“We expect this preliminary data to assist us in our planned regulatory interactions on the design and conduct of the Phase 2b clinical trial that should allow examination of dosages of 25 mg and higher to determine the optimal dosage,” Mark Diamond, CEO of Antisense Therapeutics, said in a press release.

ATL1102 improved upper limb strength and function — determined by changes in grip and pinch strength —compared with untreated boys in a prior study. This suggests a positive impact on DMD progression.

As for the experimental therapy’s ability to modulate inflammatory response, levels of T-cells containing Cd49bm decreased during treatment, but returned to roughly starting levels after dosing.

“Given that there is currently no effective treatment for non-ambulant DMD patients, we are particularly encouraged by the preliminary data from the first six patients in this trial, which suggests a positive drug effect and may also demonstrate a meaningful slowing of disease progression compared to what might otherwise have been expected,” Diamond said.

According to the release, Antisense Therapeutics is encouraged by feedback from DMD experts actively involved in the development of DMD therapies in Europe, and with whom the company is consulting to better define the clinical developmental program of ATL1102.

“It has been great to be able to include the boys with [DMD] who are no longer ambulant in a clinical trial and the participants have enjoyed being able to take part,” added Ian Woodcock, pediatric neurologist at Murdoch Children’s Research Institute and the trial’s principle investigator.

In addition to DMD, ATL1102 is also being developed as a treatment for multiple sclerosis.