April W. Armstrong, MD, MPH

An oral tyrosine kinase 2 (TYK2) inhibitor, TAK-279 (previously called NDI-034858) led to substantial skin clearance improvement for moderate-to-severe psoriasis patients compared to placebo, especially at a 5 mg dose or higher taken once per day, according to new data.

The late-breaking data—presented at the American Academy of Dermatology (AAD) 2023 Annual Meeting in New Orleans—also indicated that at the highest dose, complete skin clearance was achieved for 33% of patients at 12 weeks.

Psoriasis is a chronic, inflammatory skin disease known to affect over 3% of the adult population of the US and characterized by a number of comorbidities. This research was conducted to determine the efficacy of an oral TYK2 inhibitor known to mediate signaling from cytokines.

The data was presented at the AAD conference by April W. Armstrong, MD, MPH, professor of dermatology and associate dean of clinical research for USC’s Keck School of Medicine.

The investigators conducted a phase 2b clinical trial, recruiting patients with moderate-to-severe psoriasis who then were randomly assigned to receive 1 of 4 different doses of NDI-034858 (either 2 mg, 5 mg, 15 mg, or 30 mg once-per-day) or the placebo for a 12 week duration.

The primary endpoint for the trial was the assessment of PASI 75 (a 75% improvement in PASI score from baseline) at Week 12, with the trial being randomized, double-blind, and placebo-controlled.

The study ended up using 259 psoriasis patients who would be given different doses of NDI-034858 or the placebo.

The investigators noted that PASI 75— the primary endpoint—was achieved by a substantially higher proportion of those participants given 5 mg or higher doses compared to participants in the placebo group after 12 weeks. The former had rates of 44% to 68% compared to just 6% for the latter.

The team noted that their secondary endpoints—including PASI 90 and PASI 100—were also consistent with the primary endpoint.

As far as adverse events were concerned, events were reported in 53-62% of those taking NDI-034858, and they reported no clear dose dependence. Events were noted in 44% of those in the placebo group.
The investigators added that laboratory parameter changes were consistent with TYK2 inhibition, but the changes were not found to be dose-dependent.

They also added that there was not an imbalance in the occurrence of cytopenia across each of the groups.

References

1. Armstrong AW, 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. Paper presented at: American Academy of Dermatology 2023 Annual Meeting; March 17 – 21. New Orleans, LA. Accessed March 19, 2023.
2. Armstrong AW, Read C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA. 2020;323(19):1945–1960. doi:10.1001/jama.2020.4006.