Pfizer’s Xeljanz follow-up abrocitinib gathers momentum

Pfizer has reported new data with abrocitinib, a follow-up to its JAK inhibitor Xeljanz, which is facing increased competition from new drugs in the class.

Xeljanz (tofacitinib) is approved to treat rheumatoid arthritis, but with abrocitinib Pfizer is targeting other indications including atopic dermatitis or eczema, which will pit the orally-active JAK inhibitor against injectable antibody therapies like Sanofi/Regeneron’s Dupixent (dupilumab).

At the European Academy of Dermatology and Venereology (EADV) congress in Madrid, Pfizer presented data from a phase 3 trial – called JADE Mono-1 – which compared abrocitinib (PF-04965842) to placebo in 387 patients with moderate-to-severe atopic dermatitis.

After 12 weeks, almost 44% of the group treated with Pfizer’s JAK inhibitor had clear or almost clear skin, compared to around 8% of the placebo group, while the proportion of patients with a 75% or better improvement in symptoms came in at around 63% and 12%, respectively.

There was also a clear dose response with Pfizer’s drug, with a 200 mg dose performing better than 100 mg, and the drug hit a number of key secondary measures including pruritus (itching), one of the most debilitating symptoms in atopic dermatitis.

That efficacy looks at least as good as the level seen in trials of Dupixent – with all the usual caveats about making comparisons without head-to-head studies – and with safety data also suggesting a clean profile it looks like Pfizer has a good shot at approval.

The safety issue is particularly important as Xeljanz and other JAK inhibitors approved for rheumatoid arthritis – Eli Lilly’s Olumiant (baricitinib) and AbbVie’s Rinvoq (upadacitinib) – all have warnings on their labels about a risk of blood clots.

Dupixent was approved to treat moderate-to-severe atopic dermatitis in 2017, and is running at an annualised sales rate of around €2 billion ($2.2 billion), helped by new approvals in asthma and chronic rhinosinusitis associated with nasal polyps, according to Sanofi.

Xeljanz has developed into a blockbuster product in rheumatoid arthritis with sales of $1.8 billion last year. It is however expected to come under pressure, particularly from Rinvoq and Gilead/Galapagos’ new JAK inhibitor filgotinib, which is under regulatory review in Europe and Japan and due to be filed in the US before year-end.

Pfizer has also reported top-line results from a second phase 3 trial of abrocitinib (JADE MONO-2) and so has the two studies it needs to approach regulators for approval, although it hasn’t indicated when that might take place.

It seems to have a lead in atopic dermatitis over its rivals, but AbbVie has trials on the go for Rinvoq in this indication – including a head-to-head comparison with Dupixent due to read out next year.