Takeda's Zasocitinib Enters a High-Stakes Battle in Psoriasis with Superior PASI 100 Data

Amino Observation – Original Production by the Innovative Drug Group

Author | Wu Yue

/ 01 /

Towards “Complete Clearance”

Among the clinical study endpoints for psoriasis medications, PASI stands for Psoriasis Area and Severity Index, which is also the core quantitative indicator for assessing drug efficacy.

Among these, PASI 75 indicates a 75% improvement in skin lesions and is the baseline efficacy standard commonly adopted for early oral psoriasis treatments; PASI 90 signifies near-complete clearance of skin lesions, representing an advanced level of therapeutic efficacy. Icotyde has taken the lead in raising the bar by establishing PASI 90 as the primary endpoint, thereby advancing the efficacy goal of oral medications to a new stage of “near-complete lesion clearance.”

PASI 100 represents complete clearance, which is the most intuitive goal for patients and the ceiling of clinical efficacy. Takeda has chosen to challenge this ceiling. Data show that in the LATITUDE Atlas randomized, double-blind trial, 606 patients received either 30 mg of zasocitinib once daily or 6 mg of Sotyktu. At Week 16, over 35% of patients in the zasocitinib group achieved PASI 100, compared to approximately 14% in the Sotyktu group, representing a difference of more than 2.5-fold.

Furthermore, zasocitinib demonstrated statistical superiority across all key secondary endpoints, including an early efficacy advantage observed as early as Week 8, which is crucial for enhancing patient treatment adherence.

According to Chinwe Ukomadu, Head of Inflammatory Diseases at Takeda, patients desire clear skin; therefore, the company aims to demonstrate the value of zasocitinib by meeting a higher efficacy threshold. The implication is that Takeda does not intend to make conservative comparisons against other oral medications, but rather to evaluate its oral drug against the standards set for biologics.

"Looking back to 2022, Takeda spent $4 billion as an upfront payment and committed to a maximum of $2 billion in sales milestone payments, totaling up to $6 billion to acquire the related assets and secure zasocitinib, which was in Phase II clinical trials at the time. This deal faced significant market skepticism."

Today, zasocitinib has successively outperformed placebo and Amgen’s established oral drug Otezla in Phase 3 clinical trials, and further demonstrated superiority over Sotyktu in head-to-head studies. However, what Takeda aims to prove extends far beyond these achievements.

/ 02 /

Lessons from the Past

One reason Takeda set such aggressive targets is its confidence in technological advantages.

Takeda has repeatedly emphasized that the core advantage of zasocitinib lies in its higher TYK2 selectivity, which is more than 1 million times greater than that for other JAK enzymes, enabling 24-hour sustained inhibition of pathogenic immune pathways, whereas the activity of Sotyktu diminishes within a day.

Of course, the more critical reason is that it has no retreat. Takeda has been undergoing business restructuring and pipeline refocusing in recent years, and it needs a blockbuster immunology drug. The commercialization of Sotyktu has already demonstrated that in the highly competitive psoriasis market, oral convenience alone is far from sufficient.

The psoriasis market has long been dominated by biologics (IL-23 inhibitors and IL-17 inhibitors). Although oral small-molecule drugs have been available for some time, they have struggled to disrupt the established landscape.

PDE4 inhibitors are less efficacious than biologics, while traditional JAK inhibitors have faced repeated safety concerns; TYK2 inhibitors, however, are viewed with great promise, with market expectations once projecting peak sales for Sotyktu to reach $4 billion.

However, reality fell far short of expectations. In 2023, the first year following its approval and launch, Sotyktu’s global sales amounted to $170 million; in 2024, they reached $246 million; and in 2025, they stood at only $291 million.

Where does the problem lie? The core issues are twofold: inferior efficacy compared to biologics, and significant market access barriers.

In terms of efficacy, Sotyktu’s PASI 75 clearance rate ranges from 50% to 60%, while its PASI 90 rate is only 27%–36%. Although this outperforms Otezla, it lags significantly behind biologics such as AbbVie’s Skyrizi, which achieve PASI 90 rates of 80%–90%. A Deutsche Bank survey of 60 dermatologists ranked Sotyktu last in efficacy among nine psoriasis treatments, with only Otezla performing worse; meanwhile, 50% of the physicians rated Skyrizi as the best. Physician interviews further corroborated these findings: “Oral agents are indeed much more effective than Otezla, but can they compete with biologics? Absolutely not.”

At the market access level, Sotyktu has faced even greater challenges. Due to the long-standing dominance of biologics in the psoriasis market, it took Sotyktu a considerable amount of time to raise its national reimbursement coverage rate to approximately 65%, while also having to offer higher rebate rates. A Deutsche Bank survey revealed that more than 60% of dermatologists gave negative evaluations regarding its pricing and market access. This has naturally significantly hindered its commercial scale-up.

The market performance of Sotyktu has sounded an alarm for Takeda. To achieve peak sales of $3–6 billion, zasocitinib must deliver comprehensive superiority. For Takeda, the next challenge is a far more complex commercial battle than clinical trials.

/ 03 /

The Hard Battle Has Just Begun

The breakthroughs of Icotyde and zasocitinib signify that oral psoriasis medications are entering a brand-new phase of competition. Yet this tough battle has only just begun.

By comparing zasocitinib with Skyrizi, the benchmark drug in the global psoriasis field, the boundaries of zasocitinib’s efficacy become clearer. In two pivotal Phase III trials, Skyrizi achieved PASI 100 response rates of 36.8% and 51.0%, respectively, at Week 16, while maintaining a high PASI 90 response rate of 75%. Its long-term efficacy has also demonstrated outstanding performance.

In the absence of head-to-head data, zasocitinib’s current 16-week PASI 100 rate is roughly on par with Skyrizi’s 36.8% in UltIMMa-1, but lower than the 51.0% observed in UltIMMa-2. As an oral agent, this represents a significant breakthrough, demonstrating that oral TYK2 inhibitors have reached the threshold of top-tier biologics in terms of complete skin clearance.

However, in terms of mainstream efficacy endpoints such as PASI 90, Skyrizi continues to maintain a significant lead. Another Phase III trial previously announced by Takeda showed that the PASI 90 response rate for zasocitinib at 16 weeks ranged from 51.9% to 61.3%, which is overall lower than that of Skyrizi.

The demand for better adherence has left significant room for oral medications. The autoimmune disease sector is currently undergoing a dramatic transformation. In conditions such as psoriasis, monoclonal antibodies targeting IL-17 and IL-23 (e.g., Tremfya, Skyrizi) have pushed near-complete skin clearance rates (PASI 90/100) to their ceiling. While monoclonal antibody therapies demonstrate exceptional efficacy, the need for injections remains the primary barrier to long-term patient adherence.

Johnson & Johnson’s previously released global ENCOMPASS study results indicated that psoriasis imposes a significant disease burden and highlighted patients’ preference for oral therapies. The findings demonstrated that psoriasis creates a substantial disease burden, profoundly impacting patients’ quality of life, and further underscored the preference for oral treatment. Among patients currently receiving injectable therapies, 91.2% expressed willingness to switch to novel oral treatments with comparable efficacy and a favorable safety profile.

Clearly, Johnson & Johnson is paving the way for Icotyde. Both Icotyde and zasocitinib have demonstrated one key point in terms of efficacy: oral medications can continually approach the performance of biologics. For patients with suboptimal adherence, an orally administered, once-daily drug with efficacy comparable to that of biologics holds obvious appeal.

However, whether an oral medication can break through the fierce competition from biologics and achieve significant commercial success depends on more than just short-term efficacy. For oral drugs to gain a foothold in a market dominated by biologics, several challenges remain: Can the drug sustain high efficacy, such as PASI 100, over a period of 52 weeks or longer? How can the risk of relapse after discontinuation be controlled? Is long-term safety stable, and are there any restrictions in the regulatory labeling?

Furthermore, breakthroughs in medical insurance reimbursement and channel access are required to overcome the barriers established by established biologics such as Skyrizi; reversing dermatologists’ long-standing prescribing habits and guiding clinical practice toward novel oral agents also faces significant resistance.

In short, Takeda is stepping into a major test—a comprehensive challenge spanning clinical development to commercialization, data to market access, and physicians to patients. The clinical success of zasocitinib has already provided the first half of the answer, but the more difficult challenges of this major test lie ahead.

P.S.: Feel free to scan the QR code below to add Amin Jun on WeChat for communication.