TAS-205 Misses Primary End Point in Phase 3 DMD Trial

Ambulatory patients with Duchenne muscular dystrophy (DMD) in the REACH-DMD trial (NCT04587908) of TAS-205 showed no significant difference in time to rise (TTR) from the floor from baseline to 52 weeks—the study’s main end point—according to a press release from Taiho Pharma.1

TAS-205, an investigational therapy, is a selective hematopoietic prostaglandin D synthase (HPGDS) inhibitor being developed for DMD with any dystrophin gene mutation type. HPGDS exacerbates the inflammatory response in the muscles of patients with DMD, and TAS-205 inhibits HPGDS to control motor function decline in DMD, according to the press release.

The primary outcome measure in the ambulatory cohort in the study was mean change from baseline to week 52 in the TTR from floor, and no significant differences were seen between the treatment and control groups. | Image credit: OlegKachura - stock.adobe.com

The portion of the study including ambulatory patients was conducted in Japan. It was a placebo-controlled, multi-center, double-blind study aiming to determine the efficacy of TAS-205 in patients with DMD aged 5 years or older. In the study, patients received either oral TAS-205 or a placebo twice daily for 52 weeks. A total of 82 patients at 26 sites were enrolled between November 2020 and December 2023.

The primary outcome measure in the ambulatory cohort in the study was mean change from baseline to week 52 in the TTR from floor, and no significant differences were seen between the treatment and control groups.2 Secondary outcomes included the time measured in the TTR from the floor test, as well as the change from baseline in each measured value; change from baseline in the timed up and go test (TUG); change from baseline in the North Star Ambulatory Assessment; change from baseline in the 6-minute walk distance (6MWD) test; and values related to muscle volume.

In early phase 2 data published in Annals of Clinical and Translational Neurology in 2020, TAS-205 showed favorable safety and potential benefits in patients with DMD.3 The primary end point was change in 6MWD test measures from baseline to week 24, with measurements taken at baseline, week 12, and week 24. Secondary end points were change from baseline in TTR from floor, timed up and go test, and 10-minute walk/run test

Cardiac ultrasonography, 12-lead electrocardiography, vital sign measurements, adverse events (AEs), and adverse drug reactions were also assessed.

“When considering the results of these analyses, there were potential indications that as a result of TAS-205 administration, [Prostaglandin D2] 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 authors of the early phase 2 analysis wrote. “However, further research is needed to clarify this association.”

The full phase 3 results will be presented at an upcoming academic conference, according to the press release announcing the study’s failure to meet its primary end point.1

DMD is an inherited, incurable disorder characterized by progressive muscle weakness due to mutation of the DMD gene, which leads to inadequate levels of working dystrophin.4 Without adequate dystrophin, muscle function becomes severely compromised, and patients with DMD typically experience early mortality due to the condition. Although currently available treatments can help manage symptoms and improve patient quality of life, there is no cure for DMD.

“The prevalence of DMD is 1.9 to 3.4 per 100,000 individuals, and there are an estimated 3000 to 4000 patients in Japan,” the press release noted.1 “Currently, oral steroids and viltolarsen [Viltepso; NS Pharma] are approved, and delandistrogene moxeparvovec [Elevidys; Sarepta] has received conditional and time-limited approval for DMD in Japan; however, new treatment options are being awaited.”

References

1. Phase III clinical study with therapeutic drug for Duchenne muscular dystrophy (TAS-205) in Japan did not meet its primary endpoint. News release. Taiho Pharma. July 8, 2025. Accessed July 10, 2025. https://www.taiho.co.jp/en/release/2025/20250708.html

2. A phase 3 study of TAS-205 in patients with Duchenne muscular dystrophy (REACH-DMD). ClinicalTrials.gov. Updated August 14, 2024. Accessed July 9, 2025. https://clinicaltrials.gov/study/NCT04587908

3. Komaki H, Maegaki Y, Matsumura T, et al. Early phase 2 trial of TAS-205 in patients with Duchenne muscular dystrophy. Ann Clin Transl Neurol. 2020;7(2):181-190. doi:10.1002/acn3.50978

4. Duchenne muscular dystrophy (DMD). Muscular Dystrophy Association. Accessed July 9, 2025. https://www.mda.org/disease/duchenne-muscular-dystrophy/causes-inheritance