In the Journals

FITZROY: Filgotinib induces clinical remission in Crohn's disease

Filgotinib was superior to placebo for induction of clinical remission in patients with moderate-to-severe active Crohn’s disease, and demonstrated an acceptable safety profile, according to full results from the FITZROY study recently published in The Lancet.

Filgotinib (Galapagos) is an investigational oral Janus kinase 1 (JAK1)-selective inhibitor taken once per day.

Séverine Vermeire, MD

Séverine Vermeire

“Filgotinib could represent the first new oral treatment for [Crohn’s disease] in many years, and phase 3 trials with the compound are underway,” Séverine Vermeire, MD, of the department of gastroenterology at University Hospitals Leuven, Belgium, said in a press release. “FITZROY was the first double blind, placebo-controlled study to use centrally read endoscopies to ensure the selective recruitment of patients with active disease including mucosal ulceration.”

Between February 2014 and July 2015, Vermeire and colleagues randomly assigned 174 adults with active Crohn’s disease to receive 200 mg filgotinib (n = 130) or placebo once daily for 10 weeks.

Clinical remission, defined as a Crohn’s Disease Activity Index of less than 150 at week 10 served as the primary endpoint, which 47% of the intent-to-treat population achieved compared with 23% of the placebo group, for a difference of 24% (95% CI, 9-39; P = .0077).

“The proportion of patients achieving clinical remission with filgotinib vs. placebo increased steadily over the 10-week period,” the investigators wrote.

Based on responder status, patients were then assigned to receive 100 mg or 200 mg filgotinib or placebo once daily for an additional 10-week observation period. Although this part of the study was not powered for significance, clinical responses were maintained among responders, and nonresponders from the initial placebo group achieved clinical responses. Further, over the entire 20 weeks of the study, 9% of patients exposed to filgotinib experienced a serious treatment-emergent adverse event compared with 4% of the placebo group.

Ashwin N. Ananthakrishnan, MD, MPH

Ashwin N. Ananthakrishnan

In a related editorial, Ashwin N. Ananthakrishnan, MD, MPH, of Harvard Medical School and Massachusetts General Hospital, described the strengths of this trial’s design.

“The use of a number of clinical, endoscopic, and biochemical endpoints ensures robustness of benefit of treatment and provides support for further investigation of this therapeutic mechanism,” he wrote. “The requirement for endoscopically active disease at randomization and use of central readers to adjudicate eligibility and efficacy increased the clarity in the efficacy signal and reduced the potential of bias.”

On the other hand, a “major knowledge gap ... is that the rates of response and incremental benefit are lower in anti-TNF exposed patients compared with those naive to biologicals,” he added. “Thus, whereas new treatment options with distinct mechanisms of action are a welcome addition to our armamentarium, they might not be sufficient to meet the needs of the growing proportion of patients refractory to anti-TNF therapies.”

A trial of filgotinib in rheumatoid arthritis is ongoing, the phase 3 DIVERSITY study in Crohn’s disease was initiated in November, and the phase 2b/3 SELECTION program in ulcerative colitis began earlier this month, according to a press release from Galapagos. – by Adam Leitenberger

Disclosures: Vermeire reports she has received research funding from AbbVie, Galapagos, MSD and Takeda, speaker fees from AbbVie, Falk Pharma, Ferring, Hospira, MSD, Takeda and Tillotts, and consultancy fees from AbbVie, Celgene, Ferring, Galapagos, Genentech/Roche, Hospira, Janssen, MSD, Mundipharma, Pfizer, Second Genome, Shire and Takeda. Please see the study for a full list of all other researchers’ relevant financial disclosures. Ananathakrishnan reports he has received consultancy fees from AbbVie unrelated to this study, Merck, Takeda and Exact Sciences, and has received research funding from Merck and Amgen.

Filgotinib was superior to placebo for induction of clinical remission in patients with moderate-to-severe active Crohn’s disease, and demonstrated an acceptable safety profile, according to full results from the FITZROY study recently published in The Lancet.

Filgotinib (Galapagos) is an investigational oral Janus kinase 1 (JAK1)-selective inhibitor taken once per day.

Séverine Vermeire, MD

Séverine Vermeire

“Filgotinib could represent the first new oral treatment for [Crohn’s disease] in many years, and phase 3 trials with the compound are underway,” Séverine Vermeire, MD, of the department of gastroenterology at University Hospitals Leuven, Belgium, said in a press release. “FITZROY was the first double blind, placebo-controlled study to use centrally read endoscopies to ensure the selective recruitment of patients with active disease including mucosal ulceration.”

Between February 2014 and July 2015, Vermeire and colleagues randomly assigned 174 adults with active Crohn’s disease to receive 200 mg filgotinib (n = 130) or placebo once daily for 10 weeks.

Clinical remission, defined as a Crohn’s Disease Activity Index of less than 150 at week 10 served as the primary endpoint, which 47% of the intent-to-treat population achieved compared with 23% of the placebo group, for a difference of 24% (95% CI, 9-39; P = .0077).

“The proportion of patients achieving clinical remission with filgotinib vs. placebo increased steadily over the 10-week period,” the investigators wrote.

Based on responder status, patients were then assigned to receive 100 mg or 200 mg filgotinib or placebo once daily for an additional 10-week observation period. Although this part of the study was not powered for significance, clinical responses were maintained among responders, and nonresponders from the initial placebo group achieved clinical responses. Further, over the entire 20 weeks of the study, 9% of patients exposed to filgotinib experienced a serious treatment-emergent adverse event compared with 4% of the placebo group.

Ashwin N. Ananthakrishnan, MD, MPH

Ashwin N. Ananthakrishnan

In a related editorial, Ashwin N. Ananthakrishnan, MD, MPH, of Harvard Medical School and Massachusetts General Hospital, described the strengths of this trial’s design.

“The use of a number of clinical, endoscopic, and biochemical endpoints ensures robustness of benefit of treatment and provides support for further investigation of this therapeutic mechanism,” he wrote. “The requirement for endoscopically active disease at randomization and use of central readers to adjudicate eligibility and efficacy increased the clarity in the efficacy signal and reduced the potential of bias.”

On the other hand, a “major knowledge gap ... is that the rates of response and incremental benefit are lower in anti-TNF exposed patients compared with those naive to biologicals,” he added. “Thus, whereas new treatment options with distinct mechanisms of action are a welcome addition to our armamentarium, they might not be sufficient to meet the needs of the growing proportion of patients refractory to anti-TNF therapies.”

A trial of filgotinib in rheumatoid arthritis is ongoing, the phase 3 DIVERSITY study in Crohn’s disease was initiated in November, and the phase 2b/3 SELECTION program in ulcerative colitis began earlier this month, according to a press release from Galapagos. – by Adam Leitenberger

Disclosures: Vermeire reports she has received research funding from AbbVie, Galapagos, MSD and Takeda, speaker fees from AbbVie, Falk Pharma, Ferring, Hospira, MSD, Takeda and Tillotts, and consultancy fees from AbbVie, Celgene, Ferring, Galapagos, Genentech/Roche, Hospira, Janssen, MSD, Mundipharma, Pfizer, Second Genome, Shire and Takeda. Please see the study for a full list of all other researchers’ relevant financial disclosures. Ananathakrishnan reports he has received consultancy fees from AbbVie unrelated to this study, Merck, Takeda and Exact Sciences, and has received research funding from Merck and Amgen.