June 2, 2020
Gilead and Galapagos have announced positive topline results from the phase 2b/3 randomized, double-blind, placebo-controlled of the oral selective JAK1 inhibitor given once-daily. The results were particularly favorable for biologic-naive patients.
The study evaluated filgotinib 200mg, filgotinib 100mg and placebo in 1,348 biologic-naïve or biologic-experienced adult patients with moderate to severe active ulcerative colitis.
Filgotinib 200mg achieved all primary endpoints, including 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) at Week 10 and maintaining clinical remission at Week 58 in a significantly higher proportion of patients vs. placebo.
The 100mg dose did not achieve statistically significant clinical remission at Week 10.
In the biologic-naïve cohort A (induction trial; n=659), 52% of patients had a baseline Mayo Clinic Score (MCS) of nine or higher.
- A statistically significant higher proportion of patients treated with filgotinib 200mg achieved clinical remission at Week 10 (26% vs. 15% with placebo, p=0.0157).
In the biologic-experienced cohort B (induction trial; n=689), 74% of patients had a baseline MCS of nine or higher; 51% of patients were previously treated with two different biologic classes (anti-TNFs and integrin receptor antagonists).
- A statistically significant higher proportion of patients treated with filgotinib 200mg achieved clinical remission at Week 10 (12% vs. 4% with placebo, p=0.0103).
Patients who achieved clinical response or remission after 10 weeks of treatment with either dose were then randomized to their induction dose or placebo (2:1) and treated through Week 58 in the maintenance trial (n=558). Both doses achieved the primary endpoint in maintenance.
- At Week 58, 37% of all patients treated with 200mg achieved clinical remission vs. 11% in the placebo group (p<0.001). 24% of all patients treated with 100mg achieved clinical remission vs. 14% in the placebo group (p=0.0420)
In the induction trial, incidence of SAEs were reportedly similar in both biologic-naïve and biologic experienced cohorts and there were no deaths in the induction cohort.
- Biologic naive: 200mg: 1.2%, 100mg 4.7%, placebo 2.9%
- Biologic experienced: 200mg: 7.3%, 100 mg: 5.3%, placebo 6.3%
In the maintenance trial, 4.5% of patients treated with 200mg had an SAE vs. 0% with placebo and 4.5% of patients treated with 100mg had an SAE vs. 7.7% with placebo.
Gilead/Galapagos report low rates of serious infections, herpes zoster, venous thrombosis, pulmonary embolism and gastrointestinal perforation that were comparable across treatment groups in both induction and maintenance.
There were two deaths in the 200mg group in the maintenance portion (asthma exacerbation in a patient with pre-existing asthma and left ventricular heart failure in a patient with pre-existing atherosclerosis), but neither were deemed to be treatment related.
Detailed results will be submitted for presentation at a future scientific meeting.
These data support the filing of both doses of filgotinib in UC so that patients can step down to 100mg after the 10-week induction period. A comparable overall rate of serious AEs was reported for both doses in the maintenance phase but no details were provided for adverse events of interest and there was no breakout for biologic-naive and -experienced patients over the longer-term. Gastroenterologists will also want to know the outcomes for induction non-responders; if there is a dosing regimen that permits initial nonresponders to gain subsequent clinical remission.
Overall, the data released today are favorable; the rate of clinical remission among biologic-experienced patients is low, but this ultimately supports the argument for first-line use.
Source: Gilead/Galapagos press release