Pfizer has posted detailed phase 3 results on its rival to Sanofi and Regeneron’s atopic dermatitis drug Dupixent. The efficacy results suggest the experimental oral therapy, abrocitinib, has a shot at challenging the blockbuster biologic incumbent for a major market.
Investigators enrolled 387 adults and adolescents with moderate to severe atopic dermatitis in the phase 3 and randomized them to receive one of two doses of JAK1 inhibitor abrocitinib or placebo.
After 12 weeks, 43.8% of subjects on high-dose abrocitinib had an Investigator Global Assessment (IGA) score of clear or almost clear skin, compared to 7.9% in the placebo group. That was one of two co-primary endpoints. The other showed 62.7% of patients on high-dose abrocitinib experienced a 75% or greater improvement on the EASI symptom score, compared to 11.8% in the placebo cohort.
The results were strong enough for the trial to hit its co-primary endpoints. Pfizer will face tougher comparators than placebo if abrocitinib comes to market, but early signs suggest the drug can rise to that challenge.
Across three phase 3 trials, between 36% and 39% of people who received Dupixent had IGA scores of clear or almost clear after 16 weeks. The EASI-75 rate in those trials ranged from 44% to 69%.
The unreliability of cross-trial comparisons make it impossible to draw concrete conclusions from the data, but, at this stage, abrocitinib looks to be competitive. That impression is reinforced by results for the secondary endpoints.
Pfizer is particularly encouraged by data on pruritus, the itching that badly affects the quality of life of people with atopic dermatitis. After 12 weeks, 57.2% of people on the high dose of abrocitinib had experienced at least a four-point improvement on a pruritus scale. Pfizer saw improvements within two weeks. The 16-week rates in the Dupixent trials were 36%, 41% and 59%.
The suggestion that abrocitinib may have an edge in terms of pruritus is in line with Pfizer’s understanding of the differences between the mechanism of action of its drug and that of Dupixent.
"In addition to covering IL-4 and IL-13, which are the pathways that Dupixent targets, we think the ability of our molecule to inhibit IL-31, which is a key driver of itch, is one of the reasons why we see such rapid and profound effects on itch severity," Michael Vincent, senior vice president and chief scientific officer at Pfizer’s inflammation and immunology (I&I) unit, said.
In terms of safety and tolerability, 20.1% of patients in the high-dose arm experienced short-lasting nausea linked to abrocitinib. The next most common treatment-emergent adverse events in that arm were nasopharyngitis, 11.7%, and headache, 9.7%. The rate of serious adverse events was numerically higher in the abrocitinib arms than placebo group, 3.2% versus 1.9%, but the rate of discontinuations was lower, 5.8% versus 9.1%.
Overall, Pfizer thinks the data, which it says were reproduced in another phase 3, support its planned positioning in what is shaping up to be a big, competitive market.
"The goal is really to be able to highlight the onset of action, the magnitude of the response, both of which are really important to the patients, focusing both on the inflammation as well as the pruritus. That's how we view the uniqueness of the molecule,” Michael Corbo, SVP and chief development officer at Pfizer’s I&I unit, said.
Pfizer is now working to wrap up a third phase 3, which features Dupixent as an active comparator, and to deliver data from it in the first half of next year. The plan is to use data from the three trials to file for approval in 2020.
Dupixent won FDA approval in 2017 on the strength of strong data and has grown into a big product for Sanofi and Regeneron, racking up sales of $553 million in the second quarter. Multiple companies want to challenge Dupixent for the market, though. Pfizer looks well set to mount a serious challenge but thinks there will ultimately be space for multiple products.
"We do need alternative mechanisms of action in this disease. Dupixent is a good drug but not everybody responds the same to all therapies," Corbo said.