The investigational tyrosine kinase inhibitor TAK-279 is effective and well tolerated in patients with active psoriatic arthritis in phase 2b study
Presenter: Alan J. Kivitz, MD, President and Medical Director, Altoona Center for Clinical Research, Duncansville, PA
Efficacy and Safety Outcomes of TAK-279, a Selective Oral Tyrosine Kinase 2 (TYK2) Inhibitor, from a Randomized, Double-blind, Placebo-controlled Phase 2b Trial in Patients with Active Psoriatic Arthritis. Abstract L12. Presented Nov 14, 2023.
The investigational oral tyrosine kinase 2 (TYK2) inhibitor TAK-279 had statistically superior dose-dependent efficacy for several endpoints versus placebo in patients with active psoriatic arthritis (PsA), according to 12-week phase 2b trial results presented at the ACR Convergence 2023.
In addition, TAK-279 was well tolerated and had an acceptable safety profile consistent with what had been observed in an earlier phase 2 study in patients with psoriasis, according to researcher Alan J. Kivitz, MD, president and medical director of the Altoona Center for Clinical Research in Duncansville, PA.
“Efficacy and safety have been shown from this phase 2 study to be in line with what is expected for this mechanism of action [ie, a TYK2 inhibitor],” Dr Kivitz said in an interview.
TAK-279 is a highly selective oral allosteric inhibitor of TYK2, which mediates signaling by key cytokines involved in disease pathogenesis of PsA and other immune-mediated inflammatory diseases, according to an abstract of the study by Dr Kivitz and co-authors. Results were presented in a late-breaking poster session at the annual rheumatology meeting.
In this presentation, investigators reported on the efficacy and safety of TAK-279 in patients with active PsA treated during the 12-week trial. The phase 2b randomized, double-blind, placebo-controlled study was conducted at 45 clinical study sites across North America and in Europe.
Investigators enrolled adult patients with PsA symptoms for at least 6 months and who had at least 3 tender and 3 swollen joints despite previous treatment with a nonsteroidal anti-inflammatory drug, disease-modifying anti-rheumatic drug, or a biologic. Patients were randomized evenly to four treatment arms — oral TAK-279 at doses of 5, 15, or 30 mg, or placebo — with treatment given once daily for 12 weeks.
Of the 290 patients who started the trial, 245 completed the 12 weeks of treatment. Their median age was 49.9 years and 57.2% were female. The mean duration of disease was 4.2 years. Nearly 59% had a psoriasis body surface area of at least 3%, with a mean Psoriasis Area and Severity Index (PASI) 75 score of 6.2.
The study’s primary endpoint of ACR 20 response at week 12 was met by two dose groups, Dr Kivitz reported. The proportion of patients achieving ACR 20 was 53.3% for TAK-279 at the 15-mg dose and 54.2% for the 30-mg dose versus just 29.2% for placebo (P = .002 for both comparisons). There was no statistically significant difference in ACR 20 between the 5-mg arm and the placebo arm.
In terms of achieving secondary endpoints, the ACR 50 response rate was significantly improved in the 15- and 30-mg dose groups versus placebo at week 12. The PASI 75 response was improved in all TAK-279 groups, but it only reached statistical significance in the 30-mg group at 45.7% of patients versus 15.4% for placebo (P = .002). The PASI response with TAK-279 15 mg was 28.3% (P = .101 vs placebo).
Scores on the Physician Global Assessment of PsA improved from baseline in all TAK-279 groups as compared with placebo, reaching statistical significance for the 30-mg dose (P < .05). Minimal disease activity response rates were significantly higher in the TAK-279 15-mg and 30-mg dose groups compared with placebo with 28.0% (15 mg) and 29.2% (30 mg) versus 12.5% for placebo (P = .017). In addition, numerical improvements were seen for TAK-279 versus placebo in ACR 70 and mean change from baseline in tender/swollen joint counts.
The most common treatment-emergent adverse events with TAK-279 were nasopharyngitis, upper respiratory tract infections, headache, and rash, according to the data presented. Serious and grade 3 or greater adverse events were similar in frequency in the TAK-279 and placebo groups.
Altogether, these findings demonstrate the efficacy of a novel TYK2 inhibitor in PsA with a consistent safety profile, said Dr Kivitz.
“Based on the efficacy and safety seen, proceeding to phase 3 trials appears warranted,” Dr Kivitz added.
Takeda plans to initiate a phase 3 study of TAK-279 in psoriasis in fiscal year 2023 and PsA in fiscal year 2024, the company said in a November 7 press release.
Disclosures
Alan J. Kivitz, MD, reported receiving consulting fees from Fresenius Kabi, Genzyme, Gilead Sciences, Grunenthal, GSK, Horizon, Janssen Pharmaceuticals, Pfizer, Selecta, SynAct Pharma, and Takeda Pharmaceuticals, and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GSK, Pfizer, and UCB. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen Pharmaceuticals, Novartis, Princeton Biopartners, and UCB. He has stocks or stock options in Amgen, GSK, Gilead Sciences, Novartis, and Pfizer.
References
Rusiñol L, Puig L. Tyk2 targeting in immune-mediated inflammatory diseases. Int J Mol Sci 2023; 24(4):3391. doi:10.3390/ijms24043391
Leit S, Greenwood J, Carriero S, et al. Discovery of a potent and selective tyrosine kinase 2 inhibitor: TAK-279. J Med Chem 2023; 66(15):10473-10496. doi:10.1021/acs.jmedchem.3c00600