Potential DMD Treatment, ATL1102, Showing Safety and Muscle Strength Gain in Phase 2 Trial

The experimental therapy ATL1102 is safe and continues to show evidence of improved upper muscle strength and function in all nine non-ambulatory boys with Duchenne muscular dystrophy (DMD) in a nearly complete Phase 2 trial in Australia, updated data show.

Final results from the open-label study, testing ATL1102 at low dose, is expected in early 2020. A potentially pivotal and yearlong Phase 2b trial may follow.

ATL1102, developed by Antisense Therapeutics, 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 works to reduce the number of T-cells producing high amounts of CD49d, which have been linked to rapid and severe progression among those with DMD.

Lowering CD49d levels is also expected to reduce tissue inflammation that exacerbates muscle fiber damage, slow disease progression, and potentially improve patients’ motor function and walking ability.

The safety and tolerability of ATL1102 are being investigated in a Phase 2 trial (ACTRN12618000970246) taking place at the Royal Children’s Hospital (RCH) in Melbourne. The study enrolled nine Duchenne boys, ages 10–18, all unable to walk without assistance.

Its main goal is 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). Additional goals include assessing its effects on functional capacity, upper limb strength, and on the levels of immune cells in the blood.

Functional capacity is being evaluated using the Performance of Upper Limb Test (PUL2.0), and upper limb strength by the MyoGrip and MyoPinch tests.

Previous findings from the first six boys treated with ATL1102 showed that the therapy was safe and well-tolerated. Treatment also led to improvements in upper limb muscle strength compared to a group of untreated children in a previous study.

This update covers treatment given all nine boys, supporting the safety of ATL1102 at the 25 mg low dose. The last two patients are expected to finish being monitored in January, Antisense said in a press release.

To date, the most common adverse events are related to its subcutaneous administration, including injection site erythema (redness) and skin discoloration. No one withdrew from the study.

No serious adverse events have been recorded, and no safety concerns were reported by the trial’s Data Safety Monitoring Board.

PUL2.0 scores increased or remained stable in seven of the nine boys over the course of the trial, suggesting an overall improvement in functional capacity. MyoGrip and MyoPinch tests also showed a clear improvement in upper limb strength among children treated with ATL1102 compared to untreated boys.

“Seeing the efficacy signals of this study, conducted with a low dose in a small number of boys over a relatively short time period, is both gratifying and immensely encouraging,” William Goolsbee, Antisense’s non-executive director and chairman of the trial’s Scientific Advisory Board, said in a press release.

“[O]nly a small handful of drugs have shown indications of efficacy so early in development. In the context of DMD, we now look to have a drug,” Goolsbee added. 

Treatment also reduced the number of T-cells in the blood, including those producing large amounts of CD49d, from baseline (study’s start) to the end of treatment. These levels were seen to rise again at week 28, after treatment stopped.

The planned Phase 2b trial of ATL1102 will also be in DMD children who are unable to walk. Antisense said it has met with three European regulatory authorities in recent months to discuss details of this study’s design, goals, and duration.

It is currently planned to use higher treatment doses, and to treat those enrolled for up to one year. The regulatory agencies agreed that positive results from a Phase 2b trial, plus final data from this Phase 2 trial, might lead to ATL1102’s approval in the EU.

Talks with the U.S. Food and Drug Administration (FDA) regarding the potential trial and this DMD treatment are also planned.

“We had high expectations for ATL1102 in DMD, and this first study has certainly exceeded them with respect to its efficacy signal at the lower dose tested. The next stage of development will be in translating what we have learned into optimizing clinical benefit for the non-ambulatory boys who comprise ~50% of the total DMD population and who have no effective treatment options,” said Mark Diamond, Antisense’s CEO.