Taiho Pharmaceutical announced that its investigational Duchenne muscular dystrophy (DMD) therapy pizuglanstat (TAS-205) failed to meet the primary endpoint in a Phase III clinical trial, marking another significant setback for the DMD therapeutic landscape.
The REACH-DMD study (NCT04587908) showed no significant difference in the mean change from baseline to 52 weeks in time to rise from the floor, the primary endpoint in the ambulatory cohort. This placebo-controlled, multi-center, double-blind comparative study was conducted in Japan and enrolled male DMD patients aged 5 years and older.
Study Design and Patient Population
The ambulatory cohort enrolled 82 patients across 26 sites from November 2020 to December 2023. Patients received either TAS-205 or placebo administered orally twice daily for 52 weeks. The study was designed to evaluate the efficacy of pizuglanstat in controlling the decline in motor function in DMD patients.
Taiho Pharmaceutical, a subsidiary of the Otsuka Group, indicated that detailed results from the study will be presented at an upcoming academic conference. The company has also enrolled a non-ambulatory DMD cohort to evaluate the safety of pizuglanstat in this population, though data from this cohort has not yet been released.
Mechanism of Action
Pizuglanstat is a selective hematopoietic prostaglandin D synthase (HPGDS) inhibitor discovered by Taiho Pharmaceutical. The drug works by inhibiting HPGDS, which is involved in the progression of muscular necrosis in DMD and exacerbates the inflammatory response in DMD patients' muscles. This inhibition leads to decreased synthesis of prostaglandin D2, resulting in a reduction in necrotic muscle fibers.
The therapy was designed to be used regardless of the dystrophin gene mutation type, potentially offering a broader treatment approach for DMD patients.
Broader DMD Therapeutic Challenges
This latest failure represents another difficult moment for the DMD community. In October 2023, Sarepta and Roche's DMD gene therapy Elevidys (delandistrogene moxeparvovec-rokl) failed to meet the primary endpoint in a Phase III confirmatory trial. The therapy has also been associated with several patient deaths, prompting an FDA investigation in June 2025.
Similarly, Pfizer withdrew its DMD gene therapy, fordadistrogene movaparvovec, in June 2024 after a patient death in a Phase II trial and a failed Phase III study.
Despite these setbacks, some promising developments have emerged. Satello's SAT-3247 showed a doubling of grip strength in a Phase Ib study, and Entrada Therapeutics received EU authorization to begin a Phase I/II trial of ENTR-601-45 after the FDA lifted a two-year hold on the therapy.
Market Outlook and Current Treatment Landscape
DMD is a genetic disorder with higher prevalence in young males, caused by genetic mutations in the gene coding for dystrophin protein. The prevalence of DMD is 1.9 to 3.4 per 100,000 individuals, with an estimated 3,000 to 4,000 patients in Japan.
Currently, oral steroids and viltolarsen are approved for DMD treatment in Japan, while delandistrogene moxeparvovec has received conditional and time-limited approval. However, new treatment options remain urgently needed.
GlobalData predicts the DMD market will grow to $5.2 billion in the seven major markets by 2033, driven primarily by recent approvals of innovative therapies, notably Sarepta Therapeutics/Roche's Elevidys and Santhera Pharmaceuticals' Agamree.
Development Background
The development of TAS-205 was selected as part of the 4th Cyclic Innovation for Clinical Empowerment (CiCLE) program for fiscal 2019, operated by the Japan Agency for Medical Research and Development (AMED). The program aims to create a foundation for transforming research and development approaches in response to clinical needs and accelerating pharmaceutical product development.
Following the trial results, Otsuka shares closed 1.62% lower at ¥6,622.00 ($45.08) on July 8, compared to ¥6,731.00 ($45.82) the previous day.
