ESK-001, an investigational oral tyrosine kinase 2 (TYK2) inhibitor, shows promise in psoriasis, according to 28-week data from the open-label extension (OLE) period of the Phase 2 STRIDE clinical trial.
In the study, ESK-001 was generally well tolerated, and most patients treated with the top dose of 40mg twice daily achieved Psoriasis Area and Severity Index (PASI) 75.
Alumis Inc.’s ESK-001 is a highly selective TYK2 inhibitor currently being evaluated in the Phase 3 ONWARD clinical program for the treatment of moderate-to-severe plaque psoriasis. Full 52-week data from the open-label extension (OLE) period of its Phase 2 STRIDE study is expected in the first half of 2025.
The interim 28-week OLE data (as of March 1, 2024) showed dose-dependent sustained increases in Psoriasis Area and Severity Score (PASI) endpoint responses observed over time, with the majority of patients (93% as observed (AO, n=71), 82.7% using modified non-responder imputation (mNRI, n=81)) achieving PASI 75, the primary endpoint, at the highest dose of 40 mg twice daily.
| 40 mg twice daily | 40 mg once daily | |||||
| STRIDE Week 12 |
OLE Week 28 |
STRIDE Week 12 |
OLE Week 28 |
|||
| NRI (N=39) |
AO (N=71) |
mNRI (N=81) |
NRI (N=39) |
AO (N=70) |
mNRI (N=79) |
|
| PASI 75 (%) | 64*** | 93 | 83 | 56*** | 73 | 67 |
| PASI 90 (%) | 39*** | 72 | 63 | 26*** | 47 | 44 |
| PASI 100 (%) | 15* | 35 | 31 | 8 | 20 | 18 |
| sPGA 0/1 (%) | 59*** | 76 | 68 | 54*** | 54 | 51 |
| *p<0.05, ***p<0.001 compared to placebo | ||||||
ESK-001 continued to show a favorable safety profile in the OLE. Treatment emergent adverse event (TEAE) frequency and severity were similar across study arms, with the majority being mild-to-moderate and self-limited. In both the Phase 2 STRIDE clinical trial and the ongoing OLE, the most common TEAEs were upper respiratory tract infections, nasopharyngitis, and headaches.
“The OLE results continue to show that ESK-001 has the potential to safely and effectively inhibit the TYK2 target at the 40mg twice daily dose and deliver lasting benefits that improve over time with continued treatment,” says Dr. Jörn Drappa, Alumis’ Chief Medical Officer, in a news release. “These data reinforce our confidence in ESK-001’s potential as a best-in-class oral treatment for moderate-to-severe plaque psoriasis.”
In related news, biomarker data from the Phase 2 STRIDE clinical trial and an e-poster showed evidence that the 40 mg twice daily dose, which achieves maximal target inhibition according to blood and skin biopsy biomarkers, leads to the highest response rates. These findings support use of the 40mg twice daily dose in the ongoing Phase 3 clinical program. Also, an e-poster showed positive efficacy and safety outcomes in the Phase 2 STRIDE clinical trial and OLE with significant improvements in patients reported quality of life (DLQI) and psoriasis-associated pruritus (NRS) with clear, dose-dependent improvement observed.
The new data were presented at the 2024 European Academy of Dermatology & Venereology (EADV) Congress in Amsterdam.
