pizuglanstat (TAS-205) / Otsuka - LARVOL DELTA

Novel haematopoietic prostaglandin D2 synthase inhibitor, CLS122, alleviated clinically relevant symptoms in an atopic dermatitis-like mouse model (ISAD-RAJKA 2025) - "Potency of CLS122 was determined against clinical trial HPGDS inhibitor, TAS-205 (Taiho Pharmaceutical)...CLS122 is a potent HPGDS inhibitor, showing anti-inflammatory effects in vitro and efficacy in DNCB challenged mice. Targeting HPGDS and PGD2 for novel AD treatment offers significant advantage by symptom alleviation and its non-invasive route of administration, making it suitable for paediatric populations."

Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pediatrics • IL1B • IL6 • TNFA

Phase 1 Mass Balance Study of Pizuglanstat: An Investigational Hematopoietic Prostaglandin D Synthase Inhibitor. (PubMed, Clin Pharmacol Drug Dev) - P1 | "Two adverse drug reactions of urticaria were reported in 2 participants (33.3%); both events were nonsevere and manageable with treatment, and no other clinically significant safety events were observed. Overall, this study provides important pharmacokinetic, mass balance, and safety data to support the development of pizuglanstat as a new treatment for Duchenne muscular dystrophy."

Journal • P1 data • Dermatology • Duchenne Muscular Dystrophy • Genetic Disorders • Immunology • Muscular Dystrophy • Urticaria

A Phase 3 Study of TAS-205 in Patients With Duchenne Muscular Dystrophy（REACH-DMD） (clinicaltrials.gov) - P3 | N=104 | Active, not recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

CRBN ligand expansion for hematopoietic prostaglandin D synthase (H-PGDS) targeting PROTAC design and their in vitro ADME profiles. (PubMed, Bioorg Med Chem) - "Although all PROTACs(H-PGDS) are relatively stable toward metabolism, they had poor PAMPA values. Nevertheless, PROTAC-5 showed P values similar to TAS-205, which is in Phase 3 clinical trials, and is expected to be the key to improving the pharmacokinetics of PROTACs."

Journal • Preclinical • Targeted Protein Degradation • CRBN

Structure-activity relationship study of PROTACs against hematopoietic prostaglandin D synthase. (PubMed, RSC Med Chem) - "We recently reported that PROTAC(H-PGDS)-7 (PROTAC1), which is composed of H-PGDS inhibitor (TFC-007) and cereblon (CRBN) E3 ligase ligand (pomalidomide), showed potent H-PGDS degradation activity. All compounds showed high H-PGDS degrading activities, but PROTAC(H-PGDS)-4-TAS-205 (PROTAC3) was slightly less active than the other compounds. Molecular dynamics simulations suggested that the decrease in activity of PROTAC3 may be due to the lower stability of the CRBN-PROTAC-H-PGDS ternary complex."

Journal • Allergy • Muscular Dystrophy • Targeted Protein Degradation • CRBN

Perspectives on the advances in the pharmacotherapeutic management of Duchenne muscular dystrophy. (PubMed, Expert Opin Pharmacother) - ": Corticosteroids such as prednisone and deflazacort are routinely given to patients to treat inflammation, but their use is limited by the occurrence of side effects and a lack of standardized prescribing...Excessive cost is a barrier to patients receiving medications that have yet to have established efficacy. Additional therapies have the potential to help patients with DMD, although most are several years away from approval for patient use."

Journal • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy

Mass Balance Study of [14C] TAS-205 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Taiho Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion

Prognostic indicators of disease progression in Duchenne muscular dystrophy: A literature review and evidence synthesis. (PubMed, PLoS One) - "This study provides a current summary of prognostic indicators of disease progression in DMD, which will help inform the design of comparative analyses and future data collection initiatives in this patient population."

Biomarker • Journal • Review • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Mass Balance Study of [14C] TAS-205 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Trial primary completion date: Apr 2022 ➔ Jun 2021

Trial primary completion date

Mass Balance Study of [14C] TAS-205 in Healthy Volunteers (clinicaltrials.gov) - P1; N=6; Active, not recruiting; Sponsor: Taiho Pharmaceutical Co., Ltd.; Not yet recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Mass Balance Study of [14C] TAS-205 in Healthy Volunteers (clinicaltrials.gov) - P1; N=6; Not yet recruiting; Sponsor: Taiho Pharmaceutical Co., Ltd.

New P1 trial

A Phase 3 Study of TAS-205 in Patients With Duchenne Muscular Dystrophy（REACH-DMD） (clinicaltrials.gov) - P3; N=80; Recruiting; Sponsor: Taiho Pharmaceutical Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Taiho Pharmaceutical Begins Phase III Clinical Trial with Therapeutic Drug for Duchenne Muscular Dystrophy (TAS-205) in Japan (Taiho Press Release) - "Taiho Pharmaceutical Co., Ltd. announced today that it has begun a phase III clinical trial in Japan with its therapeutic drug (development code: TAS-205) for Duchenne muscular dystrophy (DMD)....The new trial is a placebo-controlled multicenter double-blind comparative study for ambulatory DMD patients (REACH-DMD trial) in Japan. Eighty male DMD patients aged 5 years and older will be registered for this trial, with the purpose to study the efficacy and safety of TAS-205 by orally administering TAS-205 or a placebo twice daily for 52 weeks."

Trial status • Duchenne Muscular Dystrophy

A Phase 3 Study of TAS-205 in Patients With Duchenne Muscular Dystrophy（REACH-DMD） (clinicaltrials.gov) - P3; N=80; Not yet recruiting; Sponsor: Taiho Pharmaceutical Co., Ltd.

Clinical • New P3 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

A phase I study of TAS-205 in patients with Duchenne muscular dystrophy. (PubMed, Ann Clin Transl Neurol) - "We confirmed the safety and tolerability of TAS-205 in this study. TAS-205 decreased the total urinary excretion of PGD metabolites in a dose-dependent manner, suggesting that TAS-205 might be a therapeutic option to treat DMD patients."

Clinical • Journal • P1 data • Biosimilar • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Potential synergistic effects of novel hematopoietic prostaglandin D synthase inhibitor TAS-205 and different types of anti-allergic medicine on nasal obstruction in a Guinea pig model of experimental allergic rhinitis. (PubMed, Eur J Pharmacol) - "In contrast, concomitant treatment with TAS-205 and fexofenadine, a histamine H blocker, showed inhibitory effects on late phase and early phase nasal obstruction, although the magnitude of the inhibitory effects upon combined administration was comparable to that of each single treatment. These results suggest that combined treatment with an HPGDS inhibitor and different types of anti-allergic medicine may be a promising strategy to control nasal obstruction in AR patients."

Journal

Early phase 2 trial of TAS-205 in patients with Duchenne muscular dystrophy. (PubMed, Ann Clin Transl Neurol) - P2a; "The HPGDS inhibitor TAS-205 showed a favorable safety profile in DMD patients. Further research is required to examine the effectiveness of TAS-205 in a larger trial."

Clinical • Journal • P2 data