Antisense reports positive early results from clinical trial of new drug to treat patients with Duchenne muscular dystrophy

A preliminary review of a phase two clinical trial involving an immunomodulatory therapy drug developed by Antisense Therapeutics (ASX: ANP) has shown a positive effect for patients with non-amubulant Duchenne muscular dystrophy.

The review of six patients who had completed 24 weeks of treatment with the drug ATL1102 indicated a positive effect at an immunomodulatory level, which relates to the effects on relevant immune cells.

Use of the drug at the dose tested also showed a positive effect on disease progression at a muscle strength and functioning level.

ATL1102 is an inhibitor of CD49d expression on certain immune cells (or T-cells) and it has been reported that patients with Duchenne muscular dystrophy who have a greater number of T-cells with high levels of CD49d on their surface can experience more severe and rapid disease progression.

Novel treatment

ATL1102 is being developed as a novel treatment for the inflammation that exacerbates muscle fibre damage in patients with Duchenne muscular dystrophy and which is currently treated with corticosteroids.

Corticosteroids have a range of serious side effects when used for prolonged periods such as those required by these patients.

Early indications of a positive immunomodulatory effect were underpinned by observations that certain immune cell numbers – in particular those expressing the CD49d – were trending downward during the treatment phase and returning close to starting levels post-dosing.

Valuable drug

Chief exective officer Mark Diamond said ATL1102 could become a valuable drug for an illness which currently has no effective treatment.

“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,” he said.

“We expect this preliminary data to assist us in our planned regulatory interactions on the design and conduct of a phase two b clinical trial which should allow us to examine dosages of 25 milligrams and higher to determine the optimal dosage [for patients].”

Trial endpoints

The primary endpoints of the Antisense trial related to the safety and tolerability of ATL1102 with the efficacy of the drug on patients with Duchenne muscular dystrophy assessed in terms of its effect on disease processes and progression.

“The Data Safety Monitoring Board have evaluated the safety data and recommended continuation of the trial with no safety concerns,” the company said.

“It is important to note that this is the first occasion ATL1102 has been dosed for an extended duration in this patient population of non-ambulant Duchenne muscular dystrophy patients and we expect such safety observations will be important support for the proposed longer dosing in a phase two b trial.”

The trial’s secondary endpoints assessed drug activity and efficacy and Antisense said it was “highly encouraged” that data to date is indicative of drug effect, “particularly considering the small number of patients evaluated and that the progress of the final three patients (due to complete dosing in November) appears consistent with this view that the drug is showing activity”.

The ATL1102 phase two b clinical trial will be reviewed by three European regulatory authorities at Scientific Advice meetings, with the first meeting scheduled next month.

The meetings will focus on trial design, dose escalation plans, applicability of the study end-points and study duration.

ANP expects to receive written responses from each authority in the month following each meeting.

DMD facts

Duchenne muscular dystrophy is an X-chromosome-linked disease affecting one in up to 6,000 live male births.

It occurs as a result of mutations in the dystrophin gene which cause a substantial reduction in or absence of the dystrophin protein usually found in muscle cells.

Dystrophin is one of a group of proteins that work together to strengthen muscle fibres and protect them from injury as muscles contract and relax.

Without it, muscle cells are damaged and over time, replaced with scar tissue and fat in a process called fibrosis.

Ongoing deterioration in muscle strength affects lower limbs leading to impaired mobility, and also affects upper limbs leading to further loss of function and self-care ability.

The need for wheelchair use can occur in early teenage years for patients on corticosteroids, with dysfunctions relating to respiratory, cardiac and cognitive systems also emerging.

With no intervention, the mean age of life of a patient with Duchenne muscular dystrophy is 19 years.

Ongoing use of corticosteroids has been acknowledged as providing insufficient efficacy and has been associated with significant side effects.

At midday, shares in Antisense were up 85.11% to $0.087.