SELECTION trial: Filgotinib 200 mg has demonstrated greater efficacy compared with placebo in induction and maintenance of remission in patients with moderately to severely active ulcerative colitis
Results from SELECTION, a randomized, double-blind, placebo-controlled, phase 2b/3 trial evaluating the efficacy and safety of the investigational, oral, once-daily, selective JAK1 inhibitor Filgotinib ( Jyseleca ) in 1,348 biologic-naïve or biologic-experienced adult patients with moderately to severely active ulcerative colitis, were presented.
Filgotinib 200 mg achieved all primary endpoints in the study, inducing clinical remission at week 10 and maintaining clinical remission at week 58 in a significantly higher proportion of patients compared with placebo.
Filgotinib 100 mg did not achieve statistically significant clinical remission at week 10.
In this trial, clinical remission was defined as an endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and 1 ( or more ) point(s) decrease in stool frequency from baseline to achieve a subscore of 0 or 1.
Among the biologic-naïve cohort ( Cohort A induction trial; n=659 ), 52% of patients had a baseline Mayo Clinic Score ( MCS ) of nine or higher.
In the biologically-experienced cohort ( Cohort B induction trial; n=689 ), 74% of patients had a baseline MCS of nine or higher, and 51% were previously treated with two different classes of biologics ( TNF-alpha antagonists and an integrin receptor antagonist ).
Among biologic-naïve patients, a statistically significant higher proportion of patients achieved clinical remission at week 10 when treated with Filgotinib 200 mg ( 26.1%, p=0.0157 ) compared with placebo ( 15.3% ).
Among biologic-experienced patients, a statistically significant higher proportion of patients achieved clinical remission at week 10 when treated with Filgotinib 200 mg ( 11.5%, p=0.0103 ) compared with placebo ( 4.2% ).
Patients who achieved clinical response or remission after 10 weeks of treatment with Filgotinib 100 mg or 200 mg were subsequently re-randomized to their induction dose of Filgotinib or placebo in a 2:1 ratio and treated through week 58 ( maintenance trial, n=558 ).
Both doses of filgotinib achieved the primary endpoint in this maintenance trial.
At week 58, 37.2% of biologic-naïve and biologic-experienced patients receiving Filgotinib 200 mg achieved clinical remission, compared with 11.2% treated with placebo ( p less than 0.0001 ).
Of patients receiving Filgotinib 100 mg, 23.8% achieved clinical remission at week 58, compared with 13.5% treated with placebo ( p=0.0420 ).
In the induction trial of biologic-naïve patients, the incidence of serious adverse events was similar across treatment groups ( 200 mg: 1.2%; 100 mg: 4.7%; placebo: 2.9% ).
In the induction trial of biologic-experienced patients, the incidence of serious adverse events was also similar across treatment groups ( 200 mg: 7.3%; 100 mg: 5.3%; placebo: 6.3% ).
There were no deaths in either induction cohort.
In the maintenance trial, 4.5% of patients treated with Filgotinib 200 mg experienced a serious adverse event, compared with none for their corresponding placebo; 4.5% of patients treated with Filgotinib 100 mg experienced a serious adverse event, compared with 7.7% for their corresponding placebo.
Rates 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.
Two deaths were observed in the Filgotinib 200 mg treatment group in the maintenance trial. One patient with pre-existing asthma died due to asthma exacerbation, and the second patient with pre-existing atherosclerosis died due to left ventricular heart failure per autopsy report. Neither death was assessed as related to study drug by the investigator.
Ulcerative colitis is a chronic, idiopathic inflammatory disease affecting the colon and often involves periods of remission interspersed with periods of active disease.
Common symptoms of ulcerative colitis are bloody diarrhea and rectal urgency.
Ulcerative colitis is often diagnosed in people of working age who can face debilitating flares in their symptoms and progression of disease overtime. An estimated 40% of patients experience a relapse annually and do not achieve sustained remission. ( Xagena )
Source: Gilead, 2020