Gilead and Galapagos Announce Positive Topline Results of Phase 2b/3 Trial of Filgotinib in Moderately to Severely Active Ulcerative Colitis
-- Filgotinib 200 mg Demonstrated Greater Efficacy Compared with Placebo in the Induction and Maintenance of Remission in the SELECTION Trial --
-- Rates of Adverse Events Were Low and Comparable Across Treatment Groups --
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200520005818/en/
In this trial, clinical remission was 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. Among the biologic-naïve cohort (Cohort A induction trial; n=659), 52 percent 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 percent of patients had a baseline MCS of nine or higher, and 51 percent were previously treated with two different classes of biologics (TNFα 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 percent, p=0.0157) compared with placebo (15.3 percent). 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 percent, p=0.0103) compared with placebo (4.2 percent).
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 percent of biologic-naïve and biologic-experienced patients receiving filgotinib 200 mg achieved clinical remission, compared with 11.2 percent treated with placebo (p˂0.0001).
Of patients receiving filgotinib 100 mg, 23.8 percent achieved clinical remission at Week 58, compared with 13.5 percent 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 percent; 100 mg: 4.7 percent; placebo: 2.9 percent). In the induction trial of biologic-experienced patients, the incidence of serious adverse events was also similar across treatment groups (200 mg: 7.3 percent; 100 mg: 5.3 percent; placebo: 6.3 percent). There were no deaths in either induction cohort.
In the maintenance trial, 4.5 percent of patients treated with filgotinib 200 mg experienced a serious adverse event, compared with none for their corresponding placebo; 4.5 percent of patients treated with filgotinib 100 mg experienced a serious adverse event, compared with 7.7 percent 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.
“We are encouraged by the early response as an induction therapy and the durable efficacy as a maintenance therapy observed in the SELECTION trial,” said
“We are pleased to see that SELECTION results indicate that filgotinib can help ulcerative colitis patients, including those refractory to treatment, achieve and sustain remission for more than one year,” said Dr.
UC is a chronic, idiopathic inflammatory disease affecting the colon and often involves periods of remission interspersed with periods of active disease. Common symptoms of UC are bloody diarrhea and rectal urgency. UC is often diagnosed in people of working age who can face debilitating flares in their symptoms and progression of disease overtime. An estimated 40 percent of patients experience a relapse annuallyi and do not achieve sustained remission.
Detailed results from the SELECTION trial will be submitted for presentation at a future scientific conference.
Filgotinib is an investigational agent and is not approved by the FDA or any other regulatory authority for any use. Regulatory submissions of filgotinib for the treatment of rheumatoid arthritis are currently under review by the FDA,
About the SELECTION Phase 2b/3 Trial
The SELECTION Phase 2b/3 trial is a multi-center, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of the selective JAK1 inhibitor filgotinib in adult patients with moderately to severely active ulcerative colitis. The SELECTION trial comprises 2 Induction Trials and a Maintenance Trial. The Cohort A Induction Trial enrolled biologic-naive patients, and the Cohort B Induction Trial enrolled biologic-experienced patients.
Across both induction studies, patients with moderately to severely active UC were randomized to receive filgotinib 200 mg, filgotinib 100 mg or placebo in a 2:2:1 ratio. Moderately to severely active UC was defined as a centrally read endoscopy score ≥ 2, a rectal bleeding score ≥ 1, a stool frequency score ≥ 1 and Physician Global Assessment (PGA) of ≥ 2 based on the MCS. Patients with clinical remission or response at Week 10 of induction were subsequently re-randomized to the induction dose of filgotinib or placebo in a 2:1 ratio and treated through Week 58.
The primary objectives of SELECTION are to evaluate the efficacy of filgotinib compared with placebo in establishing EBS clinical remission as determined by the
About the Filgotinib Collaborationii
This press release contains inside information within the meaning of Regulation (EU) No 596/2014 of the
Gilead Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from ongoing and additional clinical trials involving filgotinib for the treatment of ulcerative colitis and other inflammatory diseases and the possibility that the parties may be unable to complete such trials in the currently anticipated timelines or at all. Further, the regulatory submissions of filgotinib for the treatment of rheumatoid arthritis that are currently under review by the FDA,
Galapagos Forward-Looking Statement
This release may contain forward-looking statements with respect to Galapagos, including statements regarding Galapagos’ strategic ambitions, the mechanism of action and potential safety and efficacy of filgotinib, the anticipated timing of clinical studies with filgotinib and the progression and results of such studies. Galapagos cautions the reader that forward-looking statements are not guarantees of future performance. Forward-looking statements involve known and unknown risks, uncertainties and other factors which might cause the actual results, financial condition and liquidity, performance or achievements of Galapagos, or industry results, to be materially different from any historic or future results, financial conditions and liquidity, performance or achievements expressed or implied by such forward-looking statements. In addition, even if Galapagos’ results, performance, financial condition and liquidity, and the development of the industry in which it operates are consistent with such forward-looking statements, they may not be predictive of results or developments in future periods. Among the factors that may result in differences are the inherent uncertainties associated with competitive developments, clinical trial and product development activities and regulatory approval requirements (including that data from the ongoing and planned clinical research programs may not support registration or further development of filgotinib due to safety, efficacy or other reasons), Galapagos’ reliance on collaborations with third parties (including its collaboration partner for filgotinib, Gilead), and estimating the commercial potential of Galapagos’ product candidates. A further list and description of these risks, uncertainties and other risks can be found in Galapagos’
i McMullan, C. et al. BMJ Open 2017: Adapting to ulcerative colitis to try to live a ‘normal’ life. Available at: https://bmjopen.bmj.com/content/bmjopen/7/8/e017544.full.pdf. Accessed
ii Gilead & Galapagos Filgotinib Clinical Program Trial Details: FINCH 1 (NCT02889796); FINCH 2 (NCT02873936); FINCH 3 (NCT02886728); SELECTION (NCT02914522); DIVERSITY (NCT02914561); PENGUIN 1 (NCT04115748); PENGUIN 2 (NCT04115839)
+1 (650) 522-2739
+1 (650) 425-8975
+1 (781) 460-1784
Carmen Vroonen, Media
+32 473 824 874