Pfizer reports positive results from fifth phase 3 trial of Abrocitinib
New York: Pfizer Inc. has recently announced positive top-line results from the Phase 3 JADE REGIMEN study. This 52-week study investigated abrocitinib, an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor, in patients 12 and older with moderate to severe atopic dermatitis (AD) following response to initial open label induction treatment with abrocitinib 200mg.
Patients were randomized into one of three arms: 200mg, 100mg, or placebo. Both doses of abrocitinib met the primary endpoint, resulting in significantly fewer patients experiencing a loss of response requiring rescue treatment, or "flaring," compared to those randomized to placebo. Both doses also met the key secondary endpoint of a larger percentage of patients maintaining an Investigator's Global Assessment (IGA) response of clear or almost clear relative to placebo.
"Atopic dermatitis brings a lot of uncertainty and disruption to daily life, and the unpredictability of flares can make treating and managing the disease complex and frustrating," said Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development. "These latest results from our Phase 3 clinical trial program shed light on the potential abrocitinib, if approved, could have to prevent troublesome flares in patients."
The study met its primary and key secondary endpoints. After achieving clinical response in the induction period, patients who continued on the higher dose of abrocitinib, 200mg, or switched to the lower dose, 100mg, had a significantly higher probability of not experiencing a flare compared to those on placebo through week 52 (81.1%, 57.4%, and 19.1%, respectively; p<0.0001 for both doses versus placebo). In addition, patients who continued on the higher dose of abrocitinib were significantly less likely to flare than those on the lower dose (p<0.0001). Patients on either dose of abrocitinib were significantly more likely to maintain an IGA score of clear (zero) or almost clear (one) compared to placebo (p<0.0001 for both doses versus placebo).
The primary endpoint after treatment in the 12-week induction phase was the loss of response requiring rescue treatment among groups during the blinded treatment period up to 40 weeks. Loss of response requiring rescue treatment, or a "flare," was defined as a loss of at least 50% of the Eczema Area and Severity Index (EASI) response at week 12 and an IGA score of two or higher (on a five-point scale). The key secondary endpoint was the loss of response based on an IGA score of two or higher.
Out of 1,233 subjects enrolled, 798 (64.7%) responded during the initial 12-week induction period with abrocitinib monotherapy (200mg, once daily), a higher than expected responder rate compared to the monotherapy studies JADE MONO-1 and JADE MONO-2. Responder criteria was defined as achieving an IGA score of clear (zero) or almost clear (one), a reduction from IGA baseline of at least two points, and reaching an EASI-75 response compared to baseline.
No new safety signals were observed in the trial. Safety results showed that during the induction period 66.5% of patients experienced an adverse event and 1.6% experienced a serious adverse event. Following randomization, a higher percentage of patients receiving either the 200mg or 100mg dose of abrocitinib experienced adverse events compared to placebo (63.2%, 54%, and 45.3%, respectively). The percentage of patients who experienced serious adverse events were 4.9%, 1.5%, and 0.7%, respectively. More patients treated with abrocitinib discontinued from the study due to adverse events (6%, 1.9%, and 1.5%, respectively). One patient died from gastric adenocarcinoma 208 days following discontinuation from the induction treatment period, which was deemed unrelated to the study drug by the investigator.
JADE REGIMEN was a 52-week, randomized, responder-enriched, double-blind, placebo-controlled, Phase 3 withdrawal trial enrolling 1,233 subjects globally. The trial included a 12-week open-label run-in period to determine responder status to an initial induction treatment with abrocitinib monotherapy (200mg, once daily). Patients in the open-label run-in period did not receive any topical therapy. Subjects with a positive clinical response to abrocitinib induction treatment at the end of the 12-week open-label run-in period entered a 40-week, double-blind, maintenance treatment period in which they were randomized into one of three treatment arms in a 1:1:1 ratio: placebo, abrocitinib 100mg once daily, or abrocitinib 200mg once daily. Medicated topical and/or systemic standard of care therapies were not allowed during the open-label run-in and blinded treatment periods.
During the blinded treatment period, subjects meeting the protocol definition of flare entered an open-label rescue period during which they receive another 12-week course of abrocitinib 200mg once daily with topical therapy per local standard of care (SOC). In this study, flare requiring rescue treatment was defined as a loss of at least 50% of the EASI response at week 12 and an IGA score of two or higher.
Eligible subjects completing the 40 weeks of blinded treatment, or a full 12-week rescue treatment period, had the option to enter a long-term extension (LTE) study, B7451015. Subjects discontinuing early from treatment, or who were otherwise ineligible for the LTE study, entered a four-week follow up period in this study.
ADE REGIMEN is the fifth trial in the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development program. Pfizer announced complete results from the second trial in the program, JADE MONO-2, as well as top-line results from the JADE TEEN and JADE COMPARE studies, earlier this year.