A recent clinical trial at the Royal Children’s Hospital in Melbourne, Australia, has generated sufficient interest for a local biotech venture developing a promising treatment for a devastating genetic disorder to expand on its clinical trials program. Specifically, Antisense Therapeutics has engaged European regulators to discuss a pivotal clinical trial of its experimental drug candidate known as ATL1102, a potential treatment for Duchenne Muscular Dystrophy (DMD) patients.

Duchenne Muscular Dystrophy

This rare and severe form of muscular dystrophy afflicts boys age 4– includes muscle weakness and degenerates quickly. The muscle loss typically occurs first in the thighs and pelvis and then the arms. Patients often struggle to stand, and most are unable to walk by the age of 12. Scoliosis is common, and some patients struggle with intellectual disability. Females with a single copy of the defective gene may show mild symptoms. A rare disease, about 1 in 3,500 newborn boys—the disease eventually leads to death. There is currently no cure.

DMD and the Challenge

ATL1102 is caused by a mutation in the muscle dystrophin gene leading to severe progressive muscle loss and premature death. A key challenge in the management of DMD patients is to reduce the inflammation that exacerbates muscle fiber damage. Corticosteroids represent a major treatment for muscle inflammation, but they do not sufficiently suppress muscle inflammation, are not well tolerated, and can have serious side effects reports sponsor Antisense Therapeutics. Consequently, a new treatment for inflammation associated with DMD is needed.

ATL1102

Recently published DMD clinical research reveals that patients who have a greater number of T cells (immune cells) in the blood that express high levels of CD49d (CD49dhiT-cell) are associated with more severe and rapid disease progression, with an increase in the number of CD49di T cells associated with reduced walking capacity. Corticosteroids don’t reduce these cells. 

ATL1102 has been shown to block CD49d (VLA-4) expression on lymphocytes (including T cells), reduce immune cell numbers—including T cells—and to be highly effective in reducing inflammatory brain lesions in MS patients after only eight weeks of dosing.

The Royal Children’s Hospital Clinical Trial

The clinical trial of ATL1102 was conducted at the Royal Children’s Hospital in Melbourne with boys with DMD. In an interventional study, one cohort was investigated—ATL1102, 25mg/week administered SC once weekly for 24 weeks in 25kg-65kg patients (0.4mg/kg/with dose). All doses of ATL1102 were administered subcutaneously by a nurse in the hospital and by a nurse at home. Monitoring of adherence to the intervention was by diary card and by the return of the used and unused vials of investigational product and reconciliation at the hospital.

Results

The company reported that seven of the nine boys in the study had either improved their grip strength or shown no change after 24 weeks. Thomas Voit, director of Biomedical Research Centre in London noted: “Disease stabilization or indeed an improvement in functional scores in non-ambulant DMD boys is almost unheard of a very encouraging result.” No adverse events were reported.

The New Study in Europe

The sponsor, Antisense, is planning to begin a Phase IIb clinical trial in Europe in the second half of 2020. They will compare the treatment of ATLII02 to steroids over the course of a year. The European study will involve higher doses of that experimental drug ATL1102.

The Sponsor

Antisense Therapeutics is an Australian publicly traded biopharma venture (ANP.ASX) focusing on the discovery and development of novel antisense therapeutics for a variety of drug candidates including Duchenne Muscular Dystrophy (DMD), Multiple Sclerosis, and Acromegaly.

For a comprehensive company, an overview sees its 2019 annual report.

The company has ten patient families with 80 patients registered or in the process of being registered and 13 patient applications pending covering its two antisense drugs, ATL1102 and ATL1103, and their applications. Antisense Therapeutics has also licensed from Ionis Pharmaceuticals, Ionis proprietary patients, and applications directed to the antisense drug platform. The company has continuously expanded its patient portfolio.

Their drugs come from the partnership with Ionis Pharmaceuticals, a leader in antisense therapy with three drugs approved. Antisense hopes to follow in the footsteps of Boston-based Sarepta Therapeutics, which has secured a $300,000-a-year treatment for MD that works in about 14% of cases—where patients have a certain gene mutation.

The Research Site

Royal Children’s Hospital in Melbourne, Australia has been offering high-level care for Victoria’s children and their families for over 140 years. A major specialist pediatric hospital in Victoria, their care extends to children from Tasmania, southern New South Wales, and other states around Australia and overseas. They employ nearly 4,000 medical and health professionals providing a full range of services to their patients. They are designated as a state-wide major trauma center for pediatrics in Victoria and a Nationally Funded Center for cardiac and liver transplantation. 

Research

Royal Children’s Hospital partners with elite institutions to support research such as the Murdoch Children’s Research Institute (MRI) and the University of Melbourne Department of Pediatrics, along with the RCH Foundation, are both on-site with the hospital in Parkville. Dr. Ian Woodcock is the principal investigator.

Lead Research/Investigator

Dr. Ian Woodcock, MD

Call to Action: Are you based in Victoria and interested in the investigator’s perspective of the small Melbourne-based study? contact Dr. Woodcock—see the link.

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