New safety data expose potential weakness as Pfizer's abrocitinib takes on Dupixent in eczema
Last September, when Pfizer celebrated positive data from a second Phase III study of abrocitinib, many watchers applauded the efficacy but were still waiting to see whether the JAK1 inhibitor is “safe enough to be a formidable competitor to Dupixent,” the clear leader in the atopic dermatitis field. The full slate of safety data are now out and, according to one analyst, the answer is: probably not.
The broader class of JAK inhibitors has been plagued by serious side effects relating to blood that threaten to limit their adoption, and JAK1 drugs — which target a more specific subtype of the kinase — are still under heavy scrutiny.
In a note, Jefferies’ Regeneron bull Biren Amin singled out reductions in platelet count in JADE MONO-2 as a particular cause for concern.
At week 4, platelet reductions of 26% were noted for the 200mg dose, 19% in the 100mg group, and less than 1% for those on placebo. In the drug’s defense, the researchers wrote that platelet counts “returned towards baseline values thereafter despite continuation of treatment,” and that there were no reports of bleeding disorders in any treatment group.
Still, the fact that the mechanism leading to platelet reductions is unknown could be a concern, Amin noted.
Then there’s the data point that 1.9% of patients in the 100mg group reported a serious infection, compared to none on 200mg and 1.3% on placebo. Herpes zoster was observed in 2 patients taking 200mg (1.3%).
In AbbVie’s case, Amin pointed out, 1% of patients reporting serious infections, opportunistic infections and herpes zoster was enough for regulators to slap a black box warning on Rinvoq’s rheumatoid arthritis label.
“Taken together, given the safety signals around concerns for JAK1i class, initial adoption of abrocitinib might be limited to severe patients or only be used as a short course of induction before switching patients to other therapies to reduce the exposure,” he wrote.
For now, Pfizer is focusing on the bright side, emphasizing how abrocitinib can offer potential symptom relief to patients — including the bothersome itch that comes with moderate to severe atopic dermatitis. The rate of adverse events overall was also low in the trial, backing the claim that the drug was well-tolerated. Abrocitinib is also given in pill form rather than subcutaneously, offering patients a more convenient choice.
But as Sanofi and Regeneron continue to groom Dupixent — the prize gem of a foregone relationship that generated $2.32 billion in 2019 revenue — into an even bigger blockbuster, the fight is only beginning to play out.