Text | Pick up Bay
On April 23, Bristol-Myers Squibb (BMS) announced the positive results of two key Phase III clinical studies of its first-in-class oral, selective TYK2 inhibitor deucavacitinib in the treatment of moderate to severe plaque psoriasis.
Both the POETYK PSO-1 and POETYK PSO-2 studies reached the common primary endpoint, and deucravacitinib was well tolerated, with a lower rate of discontinuation due to adverse events (AEs).
Psoriasis is a widespread, chronic, and systemic immune-mediated disease that seriously affects the health, life and work of patients.
At least 100 million people worldwide are affected by this disease.
Plaque psoriasis is characterized by the obvious round or oval plaques on the skin surface covered with silvery white scales.
Although the existing systemic treatment can achieve a certain therapeutic effect, there are still many patients with moderate to severe psoriasis that are not adequately treated, or are not treated, or are not satisfied with the existing therapies.
TYK2 is a member of the JAK family and plays an important role in mediating the signal transduction of pro-inflammatory cytokines (including IL-12, IL-23 and type I interferons).
Deucravacitinib selectively binds to the TYK2 protein regulatory domain to make TYK2 in an inactive conformation, thereby inhibiting the activity of TYK2.
Since the regulatory domain of TYK2 is different from the regulatory domains of Janus kinase (JAK) 1, 2 and 3, deucravacitinib at therapeutic doses will not inhibit JAK1, JAK2 or JAK3, thereby avoiding the adverse effects related to JAK 1-3 inhibition ( AE) occurs.
Both the POETYK PSO-1 and POETYK PSO-2 studies are multicenter, randomized, double-blind controlled studies.
666 and 1,020 patients with moderate to severe plaque psoriasis were recruited, respectively.
The subjects received deucravacitinib (6 mg, Once a day), placebo or PDE-4 inhibitor aprost (30 mg, twice a day) treatment.
The main common endpoints of the two studies were compared with placebo, reaching PASI 75 (psoriasis area and severity index score improvement of 75%) and sPGA 0/1 (doctors overall assessment of skin symptoms were completely cleared/ Almost completely cleared) the proportion of subjects.
The key secondary endpoint was the proportion of subjects who reached PASI 75 and sPGA 0/1 at week 16, compared with Apster.
The results of the two studies showed that at week 16, 58.
7% and 53.
6% of the deucravacitinib group reached PASI 75, respectively, which was significantly different from the placebo group and the apremilast group (p≤0.
5% and 81.
4% of patients who reached PASI 75 at week 24 and continued to receive deucravacitinib treatment maintained PASI 75 response at week 52, respectively.
In the two studies, 53.
6% and 50.
3% of patients in the deucravacitinib group achieved sPGA 0/1, respectively, only 7.
2% and 8.
6% in the placebo group, 32.
1% and 34.
3% in the aprost group, and skin symptoms in the deucravacitinib group.
Compared with the other two groups, the number of completely cleared/almost completely cleared persons was significantly different (p≤0.
In terms of safety, in the 16th week, the incidence of serious adverse events (SAEs) in the three groups of patients were 1.
8% (deucravacitinib), 2.
9% (placebo), and 1.
Adverse reactions occurred in the deucravacitinib group.
The proportion of patients who discontinued the drug was even lower, 2.
8%, and 5.
And the laboratory value test results showed that no adverse reaction signals related to JAK1-3 were found in patients receiving deucravacitinib treatment.
In addition to being developed for the treatment of psoriasis, deucravacitinib has also been developed for the treatment of various immune diseases such as psoriatic arthritis, lupus erythematosus and inflammatory bowel disease.
Three other studies of deucravacitinib for the treatment of psoriasis (POETYK PSO-3, POETYK PSO-4, POETYK PSO-LTE) are ongoing.
Original title: Superior effect on Apster! Results of two Phase III studies of Bristol-Myers Squibb's first-in-class oral TYK-2 inhibitor announced (with PPT)