TAS5315 / Otsuka - LARVOL DELTA

Pharmacology and safety of TAS5315, a Bruton tyrosine kinase inhibitor, in healthy volunteers: First-in-human, randomized, ascending-dose studies. (PubMed, Br J Clin Pharmacol) - "These data indicate TAS5315 has potential as a novel therapeutic for immunological diseases associated with aberrant Btk signalling, including RA and CSU. Further evaluation of TAS5315 is warranted."

Journal • P1 data • Allergy • Chronic Spontaneous Urticaria • Dermatology • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Urticaria

Bruton's Tyrosine Kinase Inhibitor TAS5315 Improved Pruritus- and Wheal-Free Days in Patients with Chronic Spontaneous Urticaria (AAAAI-WAO 2025) - P2 | "Moreover, the mean number of days without pruritus/wheal was 31.6 (37.6%)/34.4 days (41.0%), 22.4 (26.7%)/26.7 days (31.8%), 20.5 (24.4%)/22.9 days (27.3%), 15.5 (19.8%)/ 13.0 days (16.8%), 25.0 (29.8%)/23.0 days (27.4%) and 8.9 (10.6%)/8.7 days (10.3%) at 4 mg, 2 mg, 1 mg, 0.5 mg, 0.25 mg TAS5315, and placebo, respectively. Conclusions TAS5315 administration resulted in marked improvements in days without pruritus and wheal over 12 weeks in CSU patients."

Clinical • Chronic Spontaneous Urticaria • Dermatology • Immunology • Pruritus • Urticaria • IL2 • ITK

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments. (PubMed, Pharmaceuticals (Basel)) - "If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine...Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies...Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition...."

Journal • Review • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • BTK • IL13 • IL4

BRUTON’S TYROSINE KINASE INHIBITOR TAS5315, AS A POTENTIAL THERAPEUTIC AGENT AGAINST CHRONIC SPONTANEOUS URTICARIA (ACAAI 2024) - "The effects of TAS5315 were compared with those of remibrutinib, a selective BTK inhibitor. Our findings suggest that TAS5315 is a potential therapeutic agent with high and sustained efficacy against CSU."

Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Pruritus • Urticaria • CD200R1

BRUTON'S TYROSINE KINASE INHIBITOR TAS5315 SHOWED LONG-LASTING HIVEFREE CONDITION IN PATIENTS WITH CHRONIC SPONTANEOUS URTICARIA (ACAAI 2024) - P2 | "TAS5315 shows improvement in CSU for eight weeks after discontinuation of 12 week-treatment. TAS5315 may be favorable for prolonged improvement of CSU with an inadequate response to H1-antihistamines."

Clinical • Late-breaking abstract • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • IL2 • ITK

A Phase 2a Study of TAS5315 in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=126 | Completed | Sponsor: Taiho Pharmaceutical Co., Ltd. | Recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A randomized, double-blind, phase 2a study of covalent Bruton's tyrosine kinase inhibitor TAS5315 in patients with chronic spontaneous urticaria with an inadequate response to H1-antihistamines (EAACI 2024) - P2 | "Conclusion This study demonstrated the preliminary clinical efficacy of TAS5315 in improving symptoms of CSU with a trend towards dose-response relationship. TAS5315 was well tolerated and potentially effective for the patients with CSU with an inadequate response to H1-antihistamines."

Clinical • Late-breaking abstract • P2a data • Immunology

Efficacy of TAS5315, a Selective and Potent Bruton's Tyrosine Kinase Inhibitor, in Attenuating IgE-Mediated Biphasic Cutaneous Anaphylaxis in Transgenic Mice (EAACI 2024) - P2 | "In contrast, TAS5315 significantly suppressed both early and late phase cutaneous anaphylaxis in a dose-dependent manner. Conclusion Our findings suggest that TAS5315 could be a compelling option for treating histamine-refractory IgE-mediated disorders, such as CSU."

Preclinical • Allergy • Immunology • CD200R1 • IL4

A Phase 2a Study of TAS5315 in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Phase classification: P2a ➔ P2

Phase classification • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Good results with newly developed drug for MTX-refractory rheumatoid arthritis [Google translation] (jiji.com) - P2 | N=91 | NCT03605251 | Sponsor: Taiho Pharmaceutical Co., Ltd. | "The rate of achievement of ACR20 in PPS at week 12, the primary endpoint, was 60.0% in the placebo group and 78.9% in the TAS5315 (4mg + 2mg) group, which tended to be higher, but there was no significant difference (P = 0.053)....At 36 weeks, 9 had bleeding events (bruising, petechiae, purpura, cerebellar hemorrhage, epistaxis). Of these, 3 patients recovered after discontinuing TAS5315. All were mild except for one case of severe cerebellar hemorrhage."

P2 data • Immunology • Rheumatoid Arthritis

Irreversible covalent Bruton's tyrosine kinase inhibitor, TAS5315 versus placebo in rheumatoid arthritis patients with inadequate response to methotrexate: a randomised, double-blind, phase IIa trial. (PubMed, Ann Rheum Dis) - P2 | "The primary endpoint was not achieved. TAS5315 appears to have some bleeding risks, but nevertheless demonstrated numerical differences, compared with placebo, in the improvement rates of all measures of RA disease activity. Future analysis of the risk-benefit of TAS5315 should be considered."

Journal • P2a data • Dermatology • Immunology • Infectious Disease • Inflammatory Arthritis • Pruritus • Rheumatoid Arthritis • Rheumatology

Novel Bruton's tyrosine kinase inhibitor TAS5315 suppresses the progression of inflammation and joint destruction in rodent collagen-induced arthritis. (PubMed, PLoS One) - "TAS5315 improved bone mineral density and bone intensity. Thus, these results suggest that TAS5315 could be a promising therapeutic option for the treatment of rheumatoid arthritis."

Journal • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD69 • CD86 • TNFA

A Phase 2a Study of TAS5315 in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2a | N=120 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Phase 2a Study of TAS5315 in Patients With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2a | N=120 | Not yet recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd.

New P2a trial • Chronic Spontaneous Urticaria • Dermatology • Urticaria

Efficacy and Safety Study of TAS5315 Compared With Placebo in Participants With Rheumatoid Arthritis. (clinicaltrials.gov) - P2; N=91; Completed; Sponsor: Taiho Pharmaceutical Co., Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Rheumatoid Arthritis • Rheumatology

Efficacy and Safety Study of TAS5315 Compared With Placebo in Participants With Rheumatoid Arthritis. (clinicaltrials.gov) - P2; N=91; Active, not recruiting; Sponsor: Taiho Pharmaceutical Co., Ltd.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • CRP

TAS5315, A NOVEL BRUTON’S TYROSINE KINASE INHIBITOR, DEMONSTRATES POTENT EFFICACY AGAINST BONE DESTRUCTION IN AN ANIMAL MODEL FOR RHEUMATOID ARTHRITIS (EULAR 2019) - "Our study demonstrates that TAS5315 would be an attractive RA therapeutic drug that could improve bone destruction as well as inflammation."

Preclinical

A PHASE 1, SINGLE AND MULTIPLE ASCENDING DOSE STUDY OF TAS5315—A NOVEL HIGHLY SELECTIVE INHIBITOR OF BRUTON’S TYROSINE KINASE—IN HEALTHY MALE VOLUNTEERS (EULAR 2019) - "TAS5315 was tolerable when administered as repeated doses of up to 8 mg once daily for 7 days. The inhibitory effect of BTK by TAS5315 was demonstrated and this provides the basis for an early Phase II study to evaluate the efficacy of TAS5315 in patients with RA."

Clinical • P1 data

Efficacy and Safety Study of TAS5315 Compared With Placebo in Participants With Rheumatoid Arthritis. (clinicaltrials.gov) - P2; N=90; Recruiting; Sponsor: Taiho Pharmaceutical Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open