Ejim Mark, M.D., Discusses Key Research on PsA and New Drug Zasocitinib

Ejim Mark, M.D., M.P.H.

Credit: Takeda Pharmaceuticals

In an interview with The Educated Patient, Ejim Mark, M.D., M.P.H., global medical unit head of Autoimmune Diseases/Rheumatology at Takeda Pharmaceuticals, discusses new data presented at the American College of Rheumatology (ACR) Convergence 2024 demonstrating the efficacy and safety of zasocitinib, a next-generation tyrosine kinase 2 (TYK2) inhibitor, in patients with psoriatic arthritis (PsA).

What role does research play in developing better treatments, and what are some of the areas of focus in PsA research today?
Ejim Mark, M.D., M.P.H.: In general, when we research new drugs, we aim to address unmet needs in the community. This involves assessing the current treatment landscape to determine whether there is a need for a new mechanism of action or a drug that better manages the signs and symptoms of a specific disease. In the case of PsA, there continues to be a significant unmet need for a treatment that is convenient and well tolerated and has a favorable benefit-risk profile. PsA affects six different domains, and it's challenging to have a single drug that effectively targets all of them. Therefore, research often focuses on developing therapies that are not only efficacious for joint symptoms but also for skin manifestations, ensuring a comprehensive approach to the disease.

In layman's terms, according to the data that will be presented at ACR, how effective is zasocitinib for managing symptoms of PsA?
EM: Zasocitinib is an investigational oral TYK2 inhibitor with next-generation selectivity, showing promise as a treatment for immune-mediated inflammatory diseases. In our phase 2b studies, zasocitinib demonstrated positive results in terms of efficacy and safety for both psoriasis and PsA. At the upcoming ACR conference, we will present two studies, including an oral presentation focusing on achieving low disease activity — a measure of the drug's effectiveness. In this trial, zasocitinib at doses of 15 mg and 30 mg significantly improved patient outcomes compared with placebo, not only in terms of signs and symptoms but also in patient-reported outcomes, such as pain reduction.

Safety is always a concern with new treatments. What do the data show about the safety of this drug?
EM: Zasocitinib exhibits over a million-fold greater selectivity for TYK2 compared with Janus kinase (JAK) 1, JAK2, and JAK3, which means it can target TYK2 more precisely without significantly affecting other pathways. In our phase 2b studies for both psoriasis and PsA, zasocitinib showed a favorable safety and benefit-risk profile, similar to the safety profile observed in the psoriasis studies. Our aim is to maintain this balance of safety and efficacy as we move into the upcoming phase 3 trials starting in March.

Are there any populations who might benefit more from this medication compared with other treatments on the market?
EM: At this stage, we don’t have any head-to-head studies comparing zasocitinib with other market treatments. However, our phase 2 results are encouraging, indicating that it is effective in treating both PsA and psoriasis. This suggests that zasocitinib may offer a valuable option for a broad range of patients.

If zasocitinib were to be approved by the Food and Drug Administration, how could it improve the lives of patients with PsA?
EM: While zasocitinib is still under investigation and has not yet been approved by any regulatory body, the results from our phase 2 studies are promising. We hope to provide a more comprehensive understanding of its benefits and safety in our upcoming phase 3 trials.

Could you expand on what the next steps for your team are?
EM: Takeda has initiated two phase 3 studies for zasocitinib in active PsA, scheduled to begin in March 2025. These trials include two different studies: LATITUDE-PSA 3001 and LATITUDE-PSA 3002. LATITUDE-PSA 3001 will involve a biologic-naive population, while LATITUDE-PSA 3002 will include a mixed population. The 3001 study will test two doses of zasocitinib against an active comparator and placebo, while 3002 will compare two doses of zasocitinib with placebo. These trials aim to enroll about 1,600 patients.

Before we wrap up, is there anything else you'd like our audience to know?
EM: I’d like to emphasize that zasocitinib, an investigational oral TYK2 inhibitor, has demonstrated promising results in phase 2b studies for both psoriasis and PsA. As we move forward with phase 3 trials, we will continue to evaluate its efficacy and safety in both conditions. The psoriasis trials are already underway, and the PsA studies are set to begin in March 2025. We are optimistic about the potential of zasocitinib to become a significant treatment option for immune-mediated inflammatory diseases.

This transcript was edited for clarity.