Pfizer reports first pivotal data for Xeljanz follow-up

Pfizer is already a player in the JAK inhibitor anti-inflammatory category with Xeljanz, but now has the first pivotal results for a drug that it hopes could sidestep safety issues with the class.

The drugmaker has reported top-line results for abrocitinib (PF-​04965842), a selective JAK1 inhibitor, in patients aged 12 or over with moderate to severe atopic dermatitis, also known as eczema. The drug outperformed placebo on two main measures of skin clearance, as well as secondary endpoints such as itching.

Xeljanz (tofacitinib), which targets JAK3 and to a lesser extent JAK1, has been approved for moderate-to-severe rheumatoid arthritis since 2012, adding new indications in active psoriatic arthritis and moderate-to-severe ulcerative colitis in 2017 and 2018, respectively.

While it has become a big seller Xeljanz, rising by a third to $1.8 billion last year, is starting to look a little precarious in the face of looming competition that may offer cleaner side-effect profiles. Earlier this year for example Pfizer was forced to switch patients with RA to a lower dose of the drug after a study suggested a link to greater cardiovascular risk.

Safety concerns have also affected Eli Lilly’s second-to-market Olumiant (baricitinib), which has been approved at two doses in Europe for RA but was only backed by the FDA for a lower, less optimal dose. Once again cardiovascular safety was behind the regulatory caution, specifically a risk of blood clots.

With competition looming from the likes of AbbVie with upadacitinib and Galapagos/Gilead with filgotinib in RA and other indications, as well as Olumiant in atopic dermatitis, Pfizer is looking to abrocitinib to shore up its JAK inhibitor franchise.

On that front, it’s a case of so far, so good with the atopic dermatitis data. The new trial shows that after 12 weeks, the drug did better than placebo in achieving clear (0) or almost clear (1) on the Investigator Global Assessment (IGA) score – with at least a two-point improvement – as well as a 75% or greater change from baseline in Eczema Area and Severity Index (EASI) score.

Some analysts are predicting that upadacitinib and filgotinib could end up dominating a multibillion-dollar market for JAK inhibitors, mainly because of their cleaner safety profiles but also because as oral drugs they could start to displace injectable biologics like AbbVie’s $20 billion blockbuster Humira (adalimumab) and Sanofi’s new Dupixent (dupilumab) in some big indications.

It will be encouraging for Pfizer that its drug showed a lower rate of treatment discontinuations than placebo, but for now that’s all that is being offered in terms of safety data.