Takeda's investigational oral tyrosine kinase 2 (TYK2) inhibitor, TAK-279, is showing promise as a convenient and effective treatment for moderate to severe plaque psoriasis. Data from a Phase 2b study published in JAMA Dermatology demonstrated significant skin clearance in patients treated with TAK-279, suggesting it could offer efficacy comparable to biologics in an oral formulation.
Phase 2b Trial Results
The Phase 2b study randomized 259 participants with moderate to severe plaque psoriasis to receive one of four daily oral doses of TAK-279 (2 mg, 5 mg, 15 mg, or 30 mg) or placebo for 12 weeks. The results showed a dose-dependent response, with PASI 75 (a 75% or greater reduction in the Psoriasis Area and Severity Index score) achieved by 18%, 44%, 68%, and 67% of patients in the respective dose groups, compared to only 6% in the placebo group. These findings suggest that TAK-279 could provide substantial relief for patients suffering from psoriasis.
According to Dr. Graham Heap, vice president and global program leader at Takeda, the company is encouraged by the Phase 2b results and has advanced TAK-279 into Phase 3 trials for psoriasis and psoriatic arthritis, as well as Phase 2 trials for inflammatory bowel disease.
The Evolving Psoriasis Treatment Landscape
The psoriasis treatment landscape has evolved significantly, with a growing emphasis on targeted oral therapies. The approval of apremilast (Otezla) in 2014 marked an early step in this direction. The 2022 approval of deucravacitinib (Sotyktu), the first selective TYK2 inhibitor, further validated TYK2 inhibition as a distinct mechanism. TAK-279 builds on this momentum, offering a potentially more convenient oral option with a targeted mechanism of action.
Advantages of Oral Therapies
Oral therapies offer several advantages over injectable biologics, including ease of administration and potentially improved patient adherence. As Dr. Heap noted, "Patients sometimes prefer a tablet if they’re already taking other daily medications, and the idea of another pill can feel less burdensome than an injection or an infusion."
Broader Applications and Future Directions
In addition to psoriasis and psoriatic arthritis, Takeda is exploring TAK-279's potential in other immune-mediated diseases, including Crohn's disease, ulcerative colitis, and systemic lupus erythematosus. These investigations could broaden the therapeutic utility of TAK-279 and address unmet needs in various autoimmune conditions.
Addressing Unmet Needs
While methotrexate remains a foundational treatment for psoriasis, it can have significant side effects. Newer, more targeted therapies like TAK-279 aim to improve efficacy while reducing the risk of broad immunosuppression. Takeda is also focusing on patient input and diverse trial design to ensure that clinical research is representative of the populations who will ultimately use the medication.
"We spend a lot of time meeting with patient organizations, both in the U.S. and globally, really trying to understand what the needs of patients are in different areas," said Dr. Heap, highlighting Takeda's commitment to patient-centric drug development.
