TAS‐205 Safe, May Slow Muscle Loss in DMD Patients, Phase 2 Data Suggest

TAS‐205 Safe, May Slow Muscle Loss in DMD Patients, Phase 2 Data Suggest

Oral treatment with TAS-205 is safe, and may delay muscle deterioration in patients with Duchenne muscular dystrophy (DMD), an early Phase 2 clinical trial suggests.

The findings were detailed in a study, “Early phase 2 trial of TAS‐205 in patients with Duchenne muscular dystrophy,” published in the journal Annals of Clinical and Translational Neurology.

Prostaglandin D2 (PGD2) is a hormone-like molecule produced by the enzyme hematopoietic prostaglandin D synthase (HPGDS). Research has shown that PGD2 itself is involved in mediating inflammation and muscle tissue necrosis (cell death caused by damage) in people with DMD, indicating that blocking PGD2 production may be an effective way to stop inflammation in these patients.

Taiho Pharmaceutical‘s TAS‐205 is a blocker of HPGDS. Work in a mouse model of DMD revealed that TAS-205 improved motor function and slowed muscle necrosis. A subsequent Phase 1 study (NCT02246478) in DMD patients found that the potential therapy led to lower amounts PGD2 in urine.

Researchers in Japan conducted a Taiho-sponsored Phase 2 clinical trial (NCT02752048) to evaluate the efficacy and safety of TAS‐205 in male DMD patients ages 5 and older.

A total of 35 patients received either TAS-205 or a placebo, both orally. Eleven received a low dose (ranging from 6.67 to 13.33 mg/kg), 12 received a higher dose (ranging from 13.33 to 26.67 mg/kg), and the remaining 12 received a placebo. Average age across the three groups was approximately 8 years.

The study’s primary goal was to test the efficacy of TAS-205, evaluated by changes in the 6‐minute walk distance (6MWD) test of exercise capacity between the start of the study (baseline) and after 24 weeks of treatment.

While 6MWD results worsened for all groups, the TAS-205 low‐dose group saw less of a decline. Those on the therapy were able to walk an extra 13.5 meters (about 44.3 feet) more than those in the placebo group.

Patients receiving the higher dose were generally able to walk 9.5 meters (31.2 feet) more than participants on placebo.

No motor function benefits were seen with three other tests: the rise from the floor test, the timed up and go test, and the 10‐meter walk/run test.

Muscle volume was measured with a computerized tomography scan. Differences between baseline and end of treatment showed that high-dose TAS‐205 lessened the decline in the patients’ thigh muscle volume compared with the placebo group. Yet the difference was not statistically significant.

In lower leg muscles, both treatment doses showed benefits, but only the higher dose reached statistical significance (in the lower right leg).

The team analyzed urine samples to investigate the presence of a byproduct of PGD2 production called tetranor‐PGDM (tPGDM). Data showed that the total amount of tPGDM in urine was lower in both TAS‐205 treatment groups compared with placebo, with 31.2% less tPGDM in the low-dose group and 25.7% less with the higher dose

The results showed “there were potential indications that as a result of TAS‐205 administration, PGD2 production was inhibited, which subsequently reduced muscle deterioration in the lower legs, thus resulting in the suppression of further declines in 6MWD in DMD patients,” the researchers said.

During the study, 80% of participants received steroid treatment alongside TAS‐205, yet no safety issues were recorded. There were no clinically significant changes in vital signs (blood pressure, pulse rate, and body temperature) or cardiac function.

In all groups, adverse events were either mild or moderate, with the exception of a serious case of asthma unrelated to TAS‐205.

“TAS‐205 showed a favorable safety profile in DMD patients,” the researchers wrote. “It is expected that TAS‐205 could potentially be used by all DMD patients … as its mechanism of action does not depend on specific gene mutations.”

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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.