Pfizer recently announced the assessment of III for adolescent patients with moderate to severe atopic dermatitis (AD) who are treated once a day with the oral JAK1 inhibitor abrocitinib (PF-04965842) for 12-18 years of age and also receiving background topical therapy The JADE TEEN (NCT03796676) study achieved positive results. The data show that both doses of abrocitinib have reached the common primary endpoint, showing improvements in skin lesion clearance, disease severity and severity, itching, etc., and overall good tolerance.
Abrocitinib is an oral small molecule that can selectively inhibit Janus kinase 1 (JAK1). Inhibition of JAK1 is thought to regulate various cytokines in the pathophysiology of atopic dermatitis (AD), including interleukin (IL)-4, IL-13, IL-31 and interferon gamma. In the United States, the FDA granted abrocitinib a breakthrough drug qualification (BTD) for the treatment of moderate to severe AD in February 2018.
It is worth mentioning that the JADE TEEN study is the fourth study successfully completed in the global development project JADE for evaluating abrocitinib in the treatment of moderate to severe atopic dermatitis (AD). The three phase III studies (JADE MONO-1, JADE MONO-2, JADE COMPARE) previously completed in this project were also successful, showing that the common primary endpoint and critical secondary endpoint related to skin lesion removal and itching relief were reached . Just recently, Pfizer announced the complete results of the second phase III study, JADE MONO-2. The company will release detailed data on other studies of the JADE project later this year.
Data from the JADE COMPARE study, combined with the results of the JADE MONO-1 and JADE MONO-2 studies, will support the submission of listing applications to regulatory agencies. Pfizer plans to start submitting a new drug application (NDA) for abrocitinib to treat moderate to severe atopic dermatitis (AD) to the US Food and Drug Administration (FDA) later this year.
Dr. Michael Corbo, Chief Development Officer, Inflammation and Immunology, Pfizer Global Product Development, said: "Up to 20% of children are affected by atopic dermatitis (AD), and the need for new treatment options that may improve care is still unmet. Children and adolescents, these findings from the JADE TEEN study build on the positive results of our previously published Phase III monotherapy study, which included patients 12 years of age and older."
Molecular structure of abrocitinib (Source: medchemexpress.cn)
JADE TEEN is a randomized, double-blind, placebo-controlled, parallel group study. A total of 285 adolescent patients with moderate to severe AD aged 12 and over to 18 years old were enrolled. In the study, this patient was randomly assigned to receive abrocitinib 200, abrocitinib 100 mg once a day, placebo for 12 weeks, and also received background topical therapy. Eligible patients who completed the 12-week treatment period may choose to enter a long-term extension (LTE) study B7451015. Patients who discontinued treatment early or did not qualify for the LTE study entered the 4-week follow-up period.
The common primary endpoint of the study was: the proportion of patients who achieved complete clearance of the lesion (0) and almost complete clearance of the lesion (1) at the 12th week of treatment by the investigator’s overall assessment (IGA) and were ≥2 points lower than the baseline level. Percentage of patients with a weekly eczema area and severity index (EASI) score that improved by at least 75% from baseline. Key secondary endpoints include: the proportion of patients with pruritus severity reduced by ≥4 points from baseline as measured by the Itching Numerical Rating Scale (PP-NRS) at weeks 2, 4, and 12 of treatment, and atopic dermatitis at week 12 of treatment The extent of pruritus and symptom rating scale (PSAAD) score decline. PSAAD is a patient report measurement scale developed by Pfizer.
The results showed that the study reached a common primary endpoint at week 12: the two-dose abrocitinib treatment group had a significantly higher proportion of patients at each primary efficacy endpoint than the placebo group. In terms of key secondary endpoints, the proportion of patients with a clinically significant reduction in the degree of pruritus was statistically significant in the 200 mg dose of abrocitinib at each time point during the second, fourth, and twelfth weeks of treatment, and in the 100 mg dose of abrocitinib group at the second week of treatment. Significantly higher than the placebo group. Although the 100 mg dose of abrocitinib group reached a significant difference at the second week, because the significant difference was not reached at the fourth week, no further tests were conducted on the key secondary endpoints of the study. Therefore, the improvement of PSAAD at other key secondary endpoints cannot be inferred.
In the study, the safety of abrocitinib is consistent with previous studies. The safety results showed that patients receiving 100 mg or 200 mg abrocitinib had a higher rate of adverse events than the placebo group (56.8%, 62.8%, and 52.1%, respectively). The proportion of patients with serious adverse events or adverse events that led to the discontinuation of the study was similar in each group, the placebo group (2.1% each), the 100 mg dose abrocitinib group (0% and 1.1%, respectively), and the 200 mg dose abrocitinib group (respectively) 1.1% and 2.1%). The full results of the study will be announced at a future medical conference.