Pfizer's JAK1 challenger to Dupixent shines in another PhIII, but safety issues still cast a shadow
Pfizer is racking up ammunition for its full-on assault against Regeneron and Sanofi’s Dupixent franchise, with the latest topline win for an oral atopic dermatitis drug that it’s steering to the FDA later this year. But the new data cut is doing little to ease safety concerns.
JADE COMPARE is the third Phase III trial in the abrocitinib eczema program. Unlike JADE MONO-1 and JADE MONO-2, which enrolled patients who either don’t respond well or can’t tolerate topical treatment, this new trial zeroed in on those also taking topical therapies on background.
This approach helps “provide data relevant to the real-world setting,” Michael Corbo, Pfizer’s chief development officer for inflammation and immunology, noted in a statement.
In this setting, abrocitinib met the co-primary endpoints at week 12, which capture two of the most common measures of eczema. The one on IGA denotes the investigator’s assessment of clear (0) or almost clear and a 2+ point reduction on a 5-point scale from baseline. The other, EASI-75, counts the proportion of patients who achieve at least 75% change from baseline in their Eczema Area and Severity Index.
While Dupixent was included as the active control, it wasn’t formally compared to abrocitinib except on a minor endpoint on relative pruritus relief at week 2. There, Pfizer’s experimental drug induced a statistically superior reduction in itch. Its execs have previously touted faster relief as a potential advantage over Dupixent.
From the limited data, Brian Skorney of Baird reckons abrocitinib has comparable efficacy, but Dupixent likely has a slight edge on safety.
Pfizer said the safety profile seen here was consistent with previous studies, which could be a problem. Among five treatment arms comprising varying doses of abrocitinib, Dupixent and placebo, adverse events were most common among the group receiving 200mg (61.9%). By comparison, 50% of the Dupixent group, 50.8% of those taking abrocitinib 100mg, and 53.4% among the two groups taking placebo experienced a side effect.
JAK inhibitors as a class have run into serious safety issues that forced regulators to limit dosing — something Pfizer’s travails with Xeljanz have underscored. It appears that abrocitinib, which targets the JAK1 subtype, is still plagued with similar problems, with previously reported instances of nausea and headache, as well as potential increased risk of thrombocytopenia and metabolic disorders.
AbbVie’s FDA approval for its oral JAK1 drug Rinvoq (for rheumatoid arthritis no less) came with a black box warning.
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, on the other hand, inhibits IL-4 and IL-13 directly.
If physicians and patients can look beyond the safety concerns — a big if — one final factor might become crucial in Pfizer’s fight: the convenience of dosing.
“While the jury is still out with respect to the comparability of the clinical profiles of Dupixent and abrocitinib, we must note that if abrocitinib provides a similar profile to Dupixent, but in a pill form, it could serve as a major threat to Regeneron’s key subcutaneous product (Dupixent),” Skorney wrote.