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

Pfizer has racked up another phase 3 success for blockbuster-in-waiting abrocitinib. Atopic dermatitis patients who received the JAK1 inhibitor were significantly less likely to suffer a flare, burnishing the data set on the drug ahead of a FDA approval decision scheduled for April.

Over the past year or so, Pfizer has delivered a series of readouts that have presented its oral drug as a challenger to Sanofi and Regeneron’s biologic Dupixent in the moderate-to-severe atopic dermatitis market. The earlier readouts enabled Pfizer to secure priority review at the FDA, teeing it up to win approval by April.

Wednesday, Pfizer shared results from another phase 3 trial. The fifth late-phase abrocitinib trial gave 200 mg of the JAK1 inhibitor to patients once a day for 12 weeks. Patients who responded were then randomized to receive placebo or 200 mg or 100 mg of abrocitinib daily for 40 weeks. 

The design enabled Pfizer to measure the rate of flares, defined as loss of response requiring a rescue treatment, in patients aged 12 and over as they stayed on 200 mg of abrocitinib or switched to another regimen. The highest probability of not experiencing a flare, 81.1%, was seen in the 200-mg cohort. The probability in the 100-mg arm was 57.4%, which was still statistically significant versus the 19.1% seen in the placebo arm.

Pfizer is seeking approval of both the 100-mg and 200-mg doses, but, based on this trial, the higher dose is more effective. The difference between the probability of flares in the two abrocitinib arms was statistically significant. 

The trial generated other evidence of the efficacy of abrocitinib. Almost two-thirds of the 1,233 subjects enrolled in the 12-week induction period responded to the 200-mg dose. The response rate was numerically higher than that seen in early trials of abrocitinib.

No new safety signals were seen in the study. More adverse events occurred in the treatment arms. The percentage of patients who experienced serious adverse events or discontinued due to reactions to treatment were higher in the abrocitinib arms, particularly the high-dose cohort. Six percent of people taking 200 mg of abrocitinib discontinued due to adverse events, compared to 1.5% of their peers on placebo. 

Safety is an area in which the biologic incumbent Dupixent may have an edge over abrocitinib, which promises to deliver comparable or better efficacy with the convenience of oral dosing. Evidence that a significant minority of abrocitinib patients suffer adverse events such as nausea and headache, coupled to the FDA’s track record of slapping black box warnings on JAK1 inhibitors, could limit use of Pfizer’s challenger.