Pfizer Announces Positive Phase 3 JADE REGIMEN Trial Results for Abrocitinib in Moderate-to-Severe Atopic Dermatitis

Compiled by Keke

On November 11, Pfizer announced positive results from the Phase 3 JADE REGIMEN clinical study evaluating abrocitinib, an investigational once-daily oral Janus kinase 1 (JAK1) inhibitor, in patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD).

Analysis showed that both the 200 mg and 100 mg doses of abrocitinib met the primary endpoint, with a significantly lower proportion of patients in the treatment groups requiring rescue therapy or experiencing acute exacerbations compared to those randomized to placebo. Both doses also met the key secondary endpoint, demonstrating a greater proportion of patients maintaining an Investigator’s Global Assessment (IGA) response of clear or almost clear compared with placebo.

The JADE REGIMEN study is a 52-week, randomized, responder-enriched, double-blind, placebo-controlled Phase 3 withdrawal trial that enrolled a total of 1,233 participants globally. The trial included a 12-week open-label run-in period to determine patients’ response status to abrocitinib monotherapy induction treatment (200 mg, once daily). Patients did not receive any topical treatments during the open-label run-in period. At the end of the 12-week run-in period, participants who demonstrated a positive clinical response to abrocitinib induction therapy entered a 40-week double-blind maintenance treatment phase, during which they were randomly assigned to one of three treatment groups: placebo, abrocitinib 100 mg, or abrocitinib 200 mg (all administered once daily). The use of concomitant topical and/or systemic standard-of-care therapies was prohibited during both the open-label run-in and the blinded treatment periods.

The results showed that, among patients who achieved a clinical response during the induction period, those who continued on a higher dose (200 mg) of abrocitinib or switched to a lower dose (100 mg) had a significantly higher probability of remaining free from flares requiring rescue therapy over 52 weeks compared with the placebo group (81.1%, 57.4%, and 19.1%, respectively; p<0.0001 for both dose groups versus placebo). Furthermore, patients who continued on the high dose of abrocitinib were significantly less likely to experience flares than those in the low-dose group (p<0.0001). Compared with the placebo group, patients receiving either dose of abrocitinib were more likely to maintain Investigator’s Global Assessment (IGA) scores of clear (0) or almost clear (1) (p<0.0001 for both doses versus placebo). The primary endpoint after the 12-week induction treatment was the absence of flares requiring rescue therapy across groups during the blinded treatment period up to Week 40. The key secondary endpoint was the absence of flares requiring rescue therapy among patients with an IGA score of ≥2.

Among the 1,233 enrolled subjects, 798 (64.7%) responded to abrocitinib monotherapy (200 mg once daily) during the initial 12-week induction period, with a response rate higher than expected compared to the JADE MONO-1 and JADE MONO-2 monotherapy studies.

Abrocitinib is an oral small-molecule drug that selectively inhibits JAK1. Inhibition of JAK1 is believed to modulate multiple cytokines involved in the pathophysiology of atopic dermatitis (AD), including interleukin (IL)-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP). In February 2018, abrocitinib received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with moderate-to-severe AD. This October, Pfizer announced that the FDA had granted Priority Review designation for its New Drug Application (NDA) seeking approval of abrocitinib at doses of 100 mg and 200 mg for the treatment of patients aged 12 years and older with moderate-to-severe AD, with a regulatory decision expected by April 2021. In granting Priority Review, the FDA determined that abrocitinib has the potential to provide significant improvements in the safety and/or effectiveness of the treatment, prevention, or diagnosis of this serious condition. Currently, the European Medicines Agency (EMA) has also accepted the Marketing Authorization Application (MAA) for this drug, with a decision anticipated in the second half of 2021.

Pfizer is awaiting abrocitinib’s emergence as a blockbuster drug, and the success of this study clearly brings it one step closer to that goal. Over the past year, Pfizer has released a series of reports positioning this oral medication as a challenger to Sanofi and Regeneron’s biologic Dupixent in the market for moderate-to-severe atopic dermatitis. While abrocitinib is expected to deliver comparable or superior efficacy via oral administration, the safety data from this release suggest that Dupixent may hold an advantage over abrocitinib. The latter caused adverse reactions such as nausea and headache in a considerable proportion of patients, which, coupled with the U.S. FDA’s boxed warning for JAK1 inhibitors, could limit the use of Pfizer’s challenger.

Nevertheless, Pfizer remains optimistic about JAK pathway inhibitors. The company believes that the JAK pathway plays a critical role in inflammatory processes, as it is involved in the signaling of more than 50 cytokines and growth factors, many of which can drive immune-mediated diseases. Therefore, in addition to abrocitinib, Pfizer has other assets deployed in its immunokinase inhibitor pipeline:

Ritlecitinib (PF-06651600): An oral JAK3/TEC family kinase inhibitor, currently in Phase 3 clinical trials for the treatment of alopecia areata (AA), and in Phase 2 studies for the treatment of vitiligo, Crohn's disease (CD), and ulcerative colitis (UC);

Brepocitinib (PF-06700841): An oral tyrosine kinase 2 (TYK2)/JAK1 inhibitor, currently under Phase 2 investigation for the topical treatment of psoriasis and atopic dermatitis (AD), as well as for psoriatic arthritis, Crohn’s disease (CD), ulcerative colitis (UC), vitiligo, systemic lupus erythematosus (SLE), alopecia areata (AA), and hidradenitis suppurativa (HS);

PF-06826647: A TYK2 inhibitor, with Phase 2 studies evaluating its efficacy in the treatment of psoriasis and HS;

PF-06650833: An interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, under Phase 2 investigation for the treatment of rheumatoid arthritis and rheumatic arthritis.

Reference Source:

1.Pfizer’s Positive Trial Results Hint at More Possibilities for Abrocitinib

2.Pfizer Announces Positive Results from Fifth Phase 3 Trial of Abrocitinib, Evaluating Safety and Efficacy Across Different Dosing Regimens

3.Pfizer's abrocitinib aces 5th phase 3 on route to FDA decision