To the untrained eye, psoriasis might look like a simple skin condition, marked by itching, scaly patches. Yet psoriasis is an immune-mediated disease with systemic consequences. As Dr. Graham Heap, vice president and global program leader at Takeda, explained during a recent interview, “Psoriasis might manifest as plaques on the skin, but it’s an immune mediated condition. So you have a lot of underlying systemic issues that go along with disease that still need to be treated.”
Globally, psoriasis presents a significant public health challenge, with roughly 125 million people living with the condition worldwide, according to the National Psoriasis Foundation.
TAK-279: Targeting psoriasis from the inside out
Takeda’s pipeline strategy for psoriasis centers on TAK-279, an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor acquired from Nimbus Therapeutics in early 2023. In a recently published Phase 2b study in JAMA Dermatology (Armstrong et al.), zasocitinib (TAK-279) demonstrated significant skin clearance in patients with moderate to severe plaque psoriasis. The study randomized 259 participants to receive one of four daily oral doses (2 mg, 5 mg, 15 mg, or 30 mg) or placebo for 12 weeks. Zasocitinib showed a dose-dependent response, with PASI 75 (indicating at least 75% skin clearance) achieved by 18%, 44%, 68%, and 67% of patients in the respective dose groups, compared to 6% in the placebo group. Additionally, the study reported no major safety concerns, with treatment-emergent adverse events occurring in 53% to 62% of zasocitinib-treated patients and 44% of placebo-treated patients. The JAMA study suggested that zasocitinib may offer “biologic-level efficacy” with a favorable safety profile in an oral formulation.
“We found the results encouraging and have moved into Phase 3 for psoriasis and psoriatic arthritis, as well as Phase 2 for inflammatory bowel disease,” Heap said.
A shifting therapeutic landscape
The psoriasis treatment landscape has shifted significantly over the past decade, with a growing emphasis on oral targeted therapies. The 2014 approval of apremilast (Otezla), an oral PDE4 inhibitor, marked an early step. This trend continued with the FDA’s 2022 approval of deucravacitinib (Sotyktu), the first selective TYK2 inhibitor for moderate to severe plaque psoriasis, validating TYK2 inhibition as a distinct mechanism separate from broader Janus kinase (JAK) inhibition. Building on this momentum, 2022 and 2023 saw other oral therapies gain approvals in dermatology and immunology, including abrocitinib (Cibinqo) for atopic dermatitis and ritlecitinib (Litfulo) for alopecia areata. Meanwhile, recent FDA approvals like spesolimab (Spevigo) for acute generalized pustular psoriasis and tapinarof (Vtama) for plaque psoriasis continue to broaden the arsenal of new treatment modalities.
Heap also underscores the convenience factor of oral therapies. “Patients sometimes prefer a tablet if they’re already taking other daily medications,” he explained, “and the idea of another pill can feel less burdensome than an injection or an infusion.” He continued: “We’ve heard from many patients that route of administration is a big deal—some prefer an oral medication, while others might be fine with injections,” Heap added. “It’s really about offering freedom of choice.”
In addition to development work for psoriasis, Takeda is actively developing TAK-279, exploring the therapy for psoriatic arthritis in fiscal year 2024. These trials, including a 52-week study for plaque psoriasis, are designed with diverse trial sites and proactive patient outreach. In addition, Takeda is exploring TAK-279’s potential in other immune-mediated diseases, with ongoing Phase 2 studies for moderately to severely active Crohn’s disease and ulcerative colitis, as well as planned investigations into systemic lupus erythematosus.
While methotrexate remains foundational, a push for targeted alternatives
While methotrexate and other broad immunosuppressants remain first-line options in many parts of the world, the call for more precise—and convenient—alternatives continues to grow. Takeda’s leadership believes TAK-279 might help address that demand.
Early Phase 2b results have fueled Takeda’s confidence, but the company’s near-term goals involve confirming these data in larger, more diverse populations. Because psoriasis often intersects with psoriatic arthritis and cardiometabolic comorbidities, a targeted oral therapy could potentially have benefits for multiple immune-mediated conditions at once. “We’re still learning about the full scope of immune-mediated disease,” Heap said. “Having a therapy that’s both highly targeted and convenient could shift how clinicians approach these overlapping syndromes.”
Dr. Graham Heap
Heap points to the broader immunosuppression associated with many Janus kinase inhibitors as one reason TYK2 inhibitors are gaining attention. “If you think about how [Janus kinase] inhibitors work, they typically inhibit JAK1, JAK2, JAK3 and TYK2 — that’s broader immunosuppression,” he said. “You inhibit a lot of cytokine pathways. We’ve seen that can yield efficacy, but it also brings in off-target safety events. So the hypothesis with a TYK2-selective inhibitor is, by just targeting IL-12, IL-23 and the Type 1 interferon pathway, you can potentially retain efficacy but maybe avoid some of that broader immunosuppression. Of course, we’ll have to see what the Phase 3 data show.”
Heap also acknowledges the continued importance of older therapies like methotrexate. “We still see methotrexate as a first-line therapy in many places around the world,” he said. While methotrexate has been around for decades and is a first-line treatment for multiple immune-mediated conditions, it can have nontrivial side effects for many patients. “I think one of the big pushes with newer, more targeted therapies is to maintain or even improve efficacy but also reduce those broader immunosuppressive effects,” Heap said.
Patient input and diverse trial design
Takeda’s approach to R&D is grounded in patient feedback. “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,” Heap said. He added that different communities can have unique socioeconomic barriers that shape their access to and perceptions of clinical research. “One of the things we spend a lot of time doing, especially on [TYK2 inhibitors], is trying to understand unmet needs across different socioeconomic classes and actually thinking about—early on—how we can make our clinical trials more representative of who’s ultimately going to take the medication.”
Heap noted that Takeda has been intentional about pursuing diversity in clinical research. “That’s a very hard thing to do; there are a lot of reasons why clinical trials look the way they do,” he said. “But we’re intentional about it. We start with patient organizations to understand how to make our trials more diverse. Sometimes that’s about site selection; sometimes it’s just education on what a clinical trial involves. The idea is to dispel myths so more people—especially in underrepresented communities—feel comfortable participating.”
While Takeda has a robust forward-looking pipeline, it also draws on a lengthy history. “Takeda’s been around since 1781—we have a 240-year history,” Heap said. “If you look back, one of the things that’s really interesting is how important quality control was to our origins. That’s part of why the company was founded, and it still matters today.” Another dimension is prioritizing the patient perspective. Heap concluded: “We think being very patient-focused aligns with that history—hopefully it’s one reason we’ve lasted so long.”
Filed Under: Biologics, clinical trials, Dermatology, Drug Discovery, Immunology
