Takeda Announces Positive Results in Phase 2b Study of Investigational TAK-279, an Oral, Once-Daily TYK2 Inhibitor

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Osaka, Japan & Cambridge, Mass., United States:

    • Results for TAK-279 (Formerly NDI-034858) Show a Significantly Greater Proportion of Patients Achieved Psoriasis Area and Severity Index (PASI) 75 at Doses ≥5mg at 12 Weeks1
    • At the Highest Dose of TAK-279, 46% of Patients Achieved PASI 90 and 33% Achieved PASI 100 at 12 Weeks, Indicating a Near-Total or Total Clearance of Skin Lesions1
    • Takeda to Start Phase 3 Plaque Psoriasis Study and Expects Topline Results for a Phase 2b Study in Psoriatic Arthritis in FY2023
    • Takeda Will Evaluate TAK-279 in Additional Immune-Mediated Diseases Including Systemic Lupus Erythematosus (SLE) and Inflammatory Bowel Disease (IBD), and Explore Further Indications in the Future

Takeda (TSE:4502/NYSE:TAK) today announced positive results from a Phase 2b clinical trial of TAK-279 (NDI-034858), a highly selective, oral allosteric tyrosine kinase 2 (TYK2) inhibitor, in patients with moderate-to-severe plaque psoriasis. The study met its primary and secondary endpoints, with a statistically significant greater proportion of TAK-279 patients achieving Psoriasis Area and Severity Index (PASI) 75, 90 and 100 in the 5mg, 15mg and 30mg dosing arms compared to placebo at 12 weeks.1 These data were presented during a late-breaking session at the American Academy of Dermatology (AAD) Annual Meeting being held March 17-21, 2023 in New Orleans.

“The Phase 2b TAK-279 results demonstrate a strong overall clinical benefit and, importantly, a significant number of patients reached PASI 90 or 100, achieving near-total or total skin clearance,” said April Armstrong, M.D., MPH, clinical investigator in the Phase 2b study and Associate Dean and Professor of Dermatology at the University of Southern California. “These results further support the potential of highly selective TYK2 inhibition to provide an effective and convenient oral treatment option for people living with moderate-to-severe plaque psoriasis who are not achieving optimal skin clearance with current therapies. I look forward to the results of future clinical trials.”

In the Phase 2b study, 259 patients were randomized (1:1:1:1:1 ratio) to receive one of four doses of TAK-279 once-daily, or placebo for 12 weeks.1 Results showed:

    • A significantly greater proportion of TAK-279 patients achieved PASI 75 (44%, 68%, 67%; 5mg, 15mg, 30mg, respectively) versus placebo (6%; p<0.001), meeting the study’s primary endpoint.1
    • A significantly greater proportion of TAK-279 patients achieved PASI 90 (21%, 45%, 46%; 5mg, 15mg, 30mg, respectively) versus placebo (0%; p<0.001), and PASI 100 (10%, 15%, 33%; 5mg, 15mg, 30mg, respectively) versus placebo (0%; p<0.001 at 30mg).1
    • A significantly greater proportion of TAK-279 patients achieved Physician Global Assessment (PGA) scores of 0/1 (27%, 49%, 52%; 5mg, 15mg, 30mg, respectively) or 0 (10%, 15%, 33%; 5mg, 15mg, 30mg, respectively) versus placebo (4% [p≤0.001] and 0% [p<0.001 at 30mg], respectively) at 12 weeks.1 A PGA score of 1 indicates almost clear skin and 0 indicates totally clear skin.2
    • There were no statistically significant differences in PASI or PGA response rates seen in the TAK-279 2mg arm* (18%, 2%, 10%, 2%; PASI 75, PASI 100, PGA 0/1, PGA 0, respectively) compared to placebo.1

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The frequency of adverse events (AEs) was 53-62% in the treatment arms and 44% in the placebo arm. Most events were mild to moderate in severity. Two serious AEs occurred in one patient (15mg) and were considered unrelated. Changes in laboratory parameters were consistent with known effects of allosteric TYK2 inhibition.1

“These compelling TAK-279 data strengthen its potential for people with moderate-to-severe plaque psoriasis. The highly selective TYK2 inhibition seen with TAK-279 spares inhibition of other members of the Janus kinase (JAK) family, which we believe should avoid JAK-related toxicities,” said Andy Plump, President R&D, Takeda. “We are confident that we can execute a comprehensive development program and deliver a potential best-in-class therapy for patients, given Takeda’s strong background in immune-mediated diseases, including inflammatory bowel disease.”

Based on these Phase 2b results, Takeda will initiate a Phase 3 study of TAK-279 in psoriasis in FY2023. Takeda expects topline results from a Phase 2b study in psoriatic arthritis in FY2023 and will be evaluating TAK-279 in additional immune-mediated diseases including systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD). Other indications will be explored in the future.

Takeda will be hosting a virtual meeting for investors and analysts to discuss these data at 7:00 p.m. EDT on Saturday, March 18 / 8:00 a.m. JST on Sunday, March 19. Please click here to participate.

Results from the Phase 2b study have no impact on the full year consolidated reported forecast for the fiscal year ending March 31, 2023 (Fiscal Year 2022).

*In the TAK-279 2mg arm, the PASI 90 response rate was 8% with a nominal p-value = 0.037 compared to placebo.1

References

    1. Armstrong A, Lynde C, Forman S, et al. Efficacy and safety results from the randomized double-blind, placebo-controlled phase 2b trial of TYK2 inhibitor NDI-034858 in moderate-to-severe psoriasis. Presented March 17-21, 2023, New Orleans, Louisiana at the 2023 American Academy of Dermatology Annual Meeting.
    1. Pascoe VL, Enamandram M, Corey KC, et al. Using the Physician Global Assessment in a Clinical Setting to Measure and Track Patient Outcomes. JAMA Dermatol. 2015;151(4):375-381. doi:10.1001/jamadermatol.2014.3513.
    1. National Institute of Arthritis and Musculoskeletal and Skin Diseases [Internet]. Psoriasis. [reviewed 2020 September; cited 2023 February 15]. Available from: https://www.niams.nih.gov/health-topics/psoriasis.
    1. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826-850. doi:10.1016/j.jaad.2008.02.039.
    1. American Academy of Dermatology Association [Internet]. Psoriasis: Overview. [cited 2023 February 15]. Available from: https://www.aad.org/public/diseases/psoriasis/what/overview.
    1. National Psoriasis Foundation [Internet]. Psoriasis Statistics. [updated 2022 December 21; cited 2023 February 15]. Available from: https://www.psoriasis.org/psoriasis-statistics/#:~:text=Psoriasis%20by%20the%20Numbers&text=125%20million%20people%20worldwide%20%E2%80%94%202,the%20World%20Psoriasis%20Day%20consortium.
    1. Nogueira M, Puig L, Torres T. JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors. Drugs. 2020;80(4):341–352. doi:10.1007/s40265-020-01261-8.
    1. Takeda Pharmaceuticals. Data on File.
    1. Gangolli EA, Carreiro S, Leit S, et al. Characterization of pharmacokinetics, pharmacodynamics, tolerability and clinical activity in Phase 1 studies of the novel allosteric tyrosine kinase 2 (TYK2) inhibitor NDI-034858. Presented May 18-21, 2022, Portland, OR at the 2022 Society for Investigative Dermatology Annual Meeting.
    1. Muromoto R, Oritani K, Matsuda T. Current understanding of the role of tyrosine kinase 2 signaling in immune responses. World J Biol Chem. 2022;13(1):1–14. doi:10.4331/wjbc.v13.i1.1.
    1. Villarino AV, Kanno Y, O’Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol. 2017;18(4):374–384. doi:10.1038/ni.3691.
    1. Gonciarz M, Pawlak-Buś K, Leszczyński P, et al. TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases. Immunotherapy. 2021;13(13):1135-1150. doi:10.2217/imt-2021-0096.
    1. Krueger JG, McInnes IB, Blauvelt A. Tyrosine kinase 2 and Janus kinase‒signal transducer and activator of transcription signaling and inhibition in plaque psoriasis. J Am Acad Dermatol. 2022;86(1):148-157. doi:10.1016/j.jaad.2021.06.869.

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