- Pfizer said Wednesday its experimental JAK1 inhibitor succeeded in a pivotal eczema study, although safety questions remain largely unanswered in a sparse initial readout.
- The Phase 3 trial tested 387 patients with moderate to severe atopic dermatitis, randomizing them between placebo and a daily oral dose of either 100 mg or 200 mg of abrocitinib. After 12 weeks, the study succeeded in clearing up skin better than placebo.
- But Wall Street analysts focused more on what Pfizer didn't disclose: detailed safety data. The broader JAK class has fallen under scrutiny, particularly on risks for thrombosis and cardiovascular events. The one specific safety figure Pfizer gave showed higher discontinuation rates in the placebo arm, at 9%, than in the active arms, each at 6%.
Pfizer's pivotal trial data would likely be fundamental to a Food and Drug Administration approval of abrocitinib. But a different study expected to report next year could drive market uptake and simultaneously instill trepidation in the current leader for atopic dermatitis.
That study pits Pfizer's oral JAK1 inhibitor head to head against Sanofi and Regeneron's Dupixent (dupilumab) in atopic dermatitis. AbbVie is also running a similar direct comparator trial with its experimental JAK inhibitor, upadacitinib. Both are expected to complete in 2020.
By being an oral drug instead of an injection, Pfizer's treatment could have an edge over Dupixent.
"The positive for Dupixent is that it is well established in the market, though we would expect an oral option would be quite attractive for some patients," Cantor Fitzgerald analyst Alethia Young wrote in a May 15 note to investors.
But that convenience may be dwarfed if safety concerns arise, which is where Wall Street analysts kept their focus Wednesday. Pfizer said further data will be presented at a scientific meeting and published in a medical journal.
The big pharma knows those safety concerns around JAK inhibitors as well as anyone. After gaining the first FDA approval for a JAK inhibitor in 2012 with Xeljanz (tofacitinib), the drugmaker built it into a blockbuster.
But a post-marketing study showed safety problems earlier this year, forcing the drugmaker to take patients off the higher-dose regimen after observing increased rates of pulmonary embolisms.
The next generation of JAK inhibitors, headlined by AbbVie's upadacitinib and Gilead's filgotinib, hope to avoid these troubles with improved safety profiles. Upadacitinib will be a first test with an FDA regulatory decision expected later this year.
The JAK market certainly has Wall Street's attention. Cantor Fitzgerald has estimated the drug class to surpass $20 billion in cumulative sales by 2026. While arthritis represents the most significant indication, atopic dermatitis would play a supplementary role in realizing that commercial vision.
For Pfizer, abrocitinib is just one experimental asset in its kinase inhibitor program. The pharma is also developing a TYK2/JAK1 inhibitor, an IRAK4 inhibitor, a TYK2 inhibitor and an oral JAK3 inhibitor.