Gilead, Galapagos claim PhIIb/III win for filgotinib in ulcerative colitis — which pales in comparison to rivals
A cut of late-stage data on one of Gilead’s highest-profile experimental drugs before remdesivir made its comeback has thrusted the company back to the pre-pandemic mode of biotech — where claims of successes are necessarily scrutinized and don’t always translate to stock gains.
Gilead and its partners at Galapagos characterized the topline Phase IIb/III results for filgotinib, their oral JAK1 inhibitor, in moderately to severely active ulcerative colitis as “positive.” But a few paragraphs down, they noted that only the 200 mg achieved the clean sweep across all primary endpoints, while the 100 mg failed to induce clinical remission at week 10.
Within each dose arm, patients were stratified by their previous experience with biologics in the two-part trial. Clinical remission — defined as “an endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and ≥ 1 point decrease in stool frequency from baseline to achieve a subscore of 0 or 1” — was observed in 26.1% of biologic-naïve patients taking 200 mg of filgotinib versus 15.3% (p=0.0157) on placebo. Among the biologic-experienced cohort, the numbers were 11.5% and 4.2%, respectively (p=0.0103).
After 10 weeks, those who achieved clinical response or remission were re-randomized to drug or placebo through week 58. At that point, 37.2% of all patients on 200 mg filgotinib maintained remission compared to 11.2% on placebo (p˂0.0001).
Summarized Cowen analyst Phil Nadeau:
The 10.8% placebo-adjusted increase in clinical remission at wk 10 is comparable to data generated by PFE’s Xeljanz, though below that demonstrated for ABBV’s Rinvoq, and likely on the lower end of investor expectations.
It was no surprise, he explained, that the trial would succeed given that the JAK inhibition mechanism had already been borne out by the rival drugs. But investors were likely hoping for a best in class profile, which the data didn’t seem to support.
In a preemptive defense, both Gilead CMO Merdad Parsey and Walid Abi-Saab, his counterpart at Galapagos, emphasized that the trial included patients who were refractory to prior treatment.
If filgotinib can’t win on efficacy, can it stand out on safety, where Xeljanz has run into trouble?
Although the data aren’t available yet, Gilead and Galapagos said “(r)ates of serious infections, herpes zoster, venous thrombosis, pulmonary embolism and gastrointestinal perforation were low and comparable across treatment groups in both the induction and maintenance phases of the study.”
The way Baird’s Brian Skorney read it, that means filgotinib might have avoided increasing CV risk, a side effect that’s plagued the JAK class.
“However, it is probably unlikely that filgotinib will be able to avoid getting a black box warning for thrombosis,” he wrote in a note.
All of that leaves plenty of room for Gilead and Galapagos to duke it out with the rivals. And the stakes are high: Nadeau estimates a market opportunity of over $4 billion from the 90,000 US UC patients who fail conventional therapy and an anti-TNF.
The companies have filed for a first approval in rheumatoid arthritis in the US, Europe and Japan, while also testing filgotinib in Crohn’s disease and other indications.