Pfizer, still chasing Dupixent, releases fifth round of data for eczema JAK inhibitor abrocitinib
Over the last several months, Pfizer has been putting together a profile of several Phase III trials for its experimental JAK1 inhibitor abrocitinib to take to regulators, in the hopes of taking down Dupixent. And on Wednesday, the big pharma released another set of positive topline data.
In what’s now the fifth Phase III to report abrocitinib data, Pfizer said fewer patients with atopic dermatitis experienced a flare up after 52 weeks at multiple dosage levels over placebo. The study, which enrolled 1,233 patients 12 and older, involved a 12-week induction followed by a 40-week blinded maintenance period.
Pfizer divvied up patients evenly into three arms — a 200 mg dose level, a 100 mg arm and the placebo group. After seeing a response in the 200 mg induction period, patients who continued into the treatment arms were significantly less likely to see their AD flare.
The probability for not flaring up in the highest dose hit 81.1% and the 100 mg saw a 57.4% likelihood, while those in the control group came in at 19.1%. Pfizer also said that these results show patients on the higher dose were significantly less likely to flare than those on the lower dose. The p-values for both of these probabilities were less than 0.0001.
Additionally, Pfizer said the responder rate in this trial after the first 12 weeks was higher than expected when compared to the previous abrocitinib studies. 798 out of the 1,233 patients, or 64.7%, saw a response.
On safety, always a question with JAK inhibitors, Pfizer saw no new safety signals in the trial. During the maintenance period, the percentage of patients who experienced serious side effects were 4.9% and 1.5% in the drug arms and 0.7% in placebo. More patients treated with abrocitinib also discontinued from the study due to adverse events — 6%, 1.9%, and 1.5% in the respective groups.
The NJ-based pharma is looking to catch Regeneron and Sanofi’s blockbuster Dupixent drug, which netted more than $1.9 billion in sales through the first half of 2020. Pfizer has a few things going in their favor as Dupixent, an IL-4/IL-13 inhibitor, is administered subcutaneously whereas abrocitinib is given orally.
But JAK inhibitors like abrocitinib have long faced scrutiny in the safety arena, handicapping drugs sometimes thought to have high sales potential. AbbVie’s Rinvoq, for example, got a black box warning after studies showed 1% of patients got a serious infection, opportunistic infection, or herpes zoster.
There have also been concerns about platelet reduction in abrocitinib, as previous studies have shown platelet counts dropping 26% for the 200 mg dose and 19% for the 100 mg group compared to essentially no reduction on placebo, though they eventually returned to normal. And one analyst said in June that the data released up to that point would not make Pfizer’s candidate safe enough to be a “formidable” competitor to Regeneron and Sanofi.
That report was followed by SVB Leerink’s Geoffrey Porges saying in July that “nearly all indications” suggest Pfizer’s candidates could be beaten to market, or by better clinical data, by other orally administered JAK challengers. Porges noted that in addition to Rinvoq, black box warnings were slapped across the entire JAK class and had previously stunted Xeljanz sales. Ultimately, Porges predicted that abrocitinib would end up relegated to second-line treatment in eczema behind Dupixent.
By blocking the Janus kinase, abrocitinib is thought to modulate multiple cytokines including IL-4, IL-13, IL-31, IL-22 and interferon gamma. Dupixent, however, inhibits IL-4 and IL-13 directly.