ADMIRE CD trial: Stem cells promote long-term fistula remission

ORLANDO – A single treatment with a suspension of allogeneic expanded adipose-derived mesenchymal stem cells, or Cx601, promotes long-term combined remission of complex perianal fistulas in patients with Crohn’s disease, according to 52-week results from the phase 3 ADMIRE CD trial.

Combined remission – a stringent endpoint consisting of closure of all treated external openings that were draining at baseline and of an absence of collections more than 2 cm of treated perianal fistulas as confirmed by blinded central MRI – was achieved in 56.3% of 103 treated patients, compared with 38.6% of 101 patients who received placebo (P = .010), Daniel C. Baumgart, MD, reported at the World Congress of Gastroenterology at ACG 2017.

This parallel-group, double-blind, multicenter study included patients who had draining, treatment-refractory, complex perianal fistulas and inactive or mildly active luminal Crohn’s disease (Crohn’s Disease Activity Index scores of 220 or less) at baseline. Those randomized to the Cx601 group received a single intralesional injection of 120 million expanded adipose-derived stem cells and standard of care. Those in the control arm received a placebo injection plus standard of care, said Dr. Baumgart of Charité Medical School, which is affiliated with both Humboldt University in Berlin and the Free University of Berlin.

Prior to receiving treatment or placebo, the patients underwent fistula curettage and, if indicated, seton placement and subsequent removal, he noted, adding that baseline concomitant medications, including immunosuppressants and anti–tumor necrosis factors, were continued without dose or regimen modification and that antibiotics were allowed for up to 4 weeks.

The 52-week findings were evaluated in the modified intention-to-treat population of patients who were randomized, were treated, and had at least one postbaseline efficacy assessment (61.8% of the study population). These findings showed that Cx601 is associated with even better outcomes at 1 year than those reported at 24 weeks; those prior results, published in The Lancet in July 2016, showed combined remission rates in the modified intention-to-treat population of 51% vs. 36% for placebo.

Furthermore, 75% of treated patients who achieved combined remission at 24 weeks maintained that remission at 52 weeks, compared with 55.9% of those in the placebo group (P = .052), Dr. Baumgart said.

Sensitivity analyses in this long-term assessment supported the long-term effectiveness of Cx601 over that of the control treatment, which provided evidence on the robustness of its advantage, he said, noting that safety results were also encouraging.

“The safety profile was similar to week 24; there were no new safety signals there at all,” he said.

The findings are of note because existing therapies for complex perianal fistulas in Crohn’s disease are often ineffective, he said, adding that fistulas occur in up to 50% of Crohn’s disease patients and that 70%-80% are complex and difficult to treat. Most are refractory to conventional anti–tumor necrosis factor therapies, and 60%-70% of patients relapse, he explained.

“If we’re honest, very few medications have been properly studied,” he said, adding that fistula patients often are excluded from industry trials.

“So [the ADMIRE CD trial] is new, design-wise, and has addressed a true medical need,” he said.

He attributed the good placebo response in this trial to the ongoing standard of care treatment in both groups, as well as to the team approach to care used in the trial. He also noted that a number of questions regarding the use of Cx601 remain to be answered, including the when the ideal retreatment time point should be, whether the treatment can be used for rectovaginal fistulas, and which patients should not receive treatment.

“So there is a lot to learn still, but I think it’s a revolutionary step forward, compared to what we have today, due to the trial design, which I think is robust, and also the encouraging outcomes,” he said.

The ADMIRE CD trial was sponsored by TiGenix SAU. Dr. Baumgart has received consulting fees and nonfinancial support from AbbVie, Biogen, and BMS.

[email protected]

ORLANDO – A single treatment with a suspension of allogeneic expanded adipose-derived mesenchymal stem cells, or Cx601, promotes long-term combined remission of complex perianal fistulas in patients with Crohn’s disease, according to 52-week results from the phase 3 ADMIRE CD trial.

Combined remission – a stringent endpoint consisting of closure of all treated external openings that were draining at baseline and of an absence of collections more than 2 cm of treated perianal fistulas as confirmed by blinded central MRI – was achieved in 56.3% of 103 treated patients, compared with 38.6% of 101 patients who received placebo (P = .010), Daniel C. Baumgart, MD, reported at the World Congress of Gastroenterology at ACG 2017.

This parallel-group, double-blind, multicenter study included patients who had draining, treatment-refractory, complex perianal fistulas and inactive or mildly active luminal Crohn’s disease (Crohn’s Disease Activity Index scores of 220 or less) at baseline. Those randomized to the Cx601 group received a single intralesional injection of 120 million expanded adipose-derived stem cells and standard of care. Those in the control arm received a placebo injection plus standard of care, said Dr. Baumgart of Charité Medical School, which is affiliated with both Humboldt University in Berlin and the Free University of Berlin.

Prior to receiving treatment or placebo, the patients underwent fistula curettage and, if indicated, seton placement and subsequent removal, he noted, adding that baseline concomitant medications, including immunosuppressants and anti–tumor necrosis factors, were continued without dose or regimen modification and that antibiotics were allowed for up to 4 weeks.

The 52-week findings were evaluated in the modified intention-to-treat population of patients who were randomized, were treated, and had at least one postbaseline efficacy assessment (61.8% of the study population). These findings showed that Cx601 is associated with even better outcomes at 1 year than those reported at 24 weeks; those prior results, published in The Lancet in July 2016, showed combined remission rates in the modified intention-to-treat population of 51% vs. 36% for placebo.

Furthermore, 75% of treated patients who achieved combined remission at 24 weeks maintained that remission at 52 weeks, compared with 55.9% of those in the placebo group (P = .052), Dr. Baumgart said.

Sensitivity analyses in this long-term assessment supported the long-term effectiveness of Cx601 over that of the control treatment, which provided evidence on the robustness of its advantage, he said, noting that safety results were also encouraging.

“The safety profile was similar to week 24; there were no new safety signals there at all,” he said.

The findings are of note because existing therapies for complex perianal fistulas in Crohn’s disease are often ineffective, he said, adding that fistulas occur in up to 50% of Crohn’s disease patients and that 70%-80% are complex and difficult to treat. Most are refractory to conventional anti–tumor necrosis factor therapies, and 60%-70% of patients relapse, he explained.

“If we’re honest, very few medications have been properly studied,” he said, adding that fistula patients often are excluded from industry trials.

“So [the ADMIRE CD trial] is new, design-wise, and has addressed a true medical need,” he said.

He attributed the good placebo response in this trial to the ongoing standard of care treatment in both groups, as well as to the team approach to care used in the trial. He also noted that a number of questions regarding the use of Cx601 remain to be answered, including the when the ideal retreatment time point should be, whether the treatment can be used for rectovaginal fistulas, and which patients should not receive treatment.

“So there is a lot to learn still, but I think it’s a revolutionary step forward, compared to what we have today, due to the trial design, which I think is robust, and also the encouraging outcomes,” he said.

The ADMIRE CD trial was sponsored by TiGenix SAU. Dr. Baumgart has received consulting fees and nonfinancial support from AbbVie, Biogen, and BMS.

[email protected]

ORLANDO – A single treatment with a suspension of allogeneic expanded adipose-derived mesenchymal stem cells, or Cx601, promotes long-term combined remission of complex perianal fistulas in patients with Crohn’s disease, according to 52-week results from the phase 3 ADMIRE CD trial.

Combined remission – a stringent endpoint consisting of closure of all treated external openings that were draining at baseline and of an absence of collections more than 2 cm of treated perianal fistulas as confirmed by blinded central MRI – was achieved in 56.3% of 103 treated patients, compared with 38.6% of 101 patients who received placebo (P = .010), Daniel C. Baumgart, MD, reported at the World Congress of Gastroenterology at ACG 2017.

This parallel-group, double-blind, multicenter study included patients who had draining, treatment-refractory, complex perianal fistulas and inactive or mildly active luminal Crohn’s disease (Crohn’s Disease Activity Index scores of 220 or less) at baseline. Those randomized to the Cx601 group received a single intralesional injection of 120 million expanded adipose-derived stem cells and standard of care. Those in the control arm received a placebo injection plus standard of care, said Dr. Baumgart of Charité Medical School, which is affiliated with both Humboldt University in Berlin and the Free University of Berlin.

Prior to receiving treatment or placebo, the patients underwent fistula curettage and, if indicated, seton placement and subsequent removal, he noted, adding that baseline concomitant medications, including immunosuppressants and anti–tumor necrosis factors, were continued without dose or regimen modification and that antibiotics were allowed for up to 4 weeks.

The 52-week findings were evaluated in the modified intention-to-treat population of patients who were randomized, were treated, and had at least one postbaseline efficacy assessment (61.8% of the study population). These findings showed that Cx601 is associated with even better outcomes at 1 year than those reported at 24 weeks; those prior results, published in The Lancet in July 2016, showed combined remission rates in the modified intention-to-treat population of 51% vs. 36% for placebo.

Furthermore, 75% of treated patients who achieved combined remission at 24 weeks maintained that remission at 52 weeks, compared with 55.9% of those in the placebo group (P = .052), Dr. Baumgart said.

Sensitivity analyses in this long-term assessment supported the long-term effectiveness of Cx601 over that of the control treatment, which provided evidence on the robustness of its advantage, he said, noting that safety results were also encouraging.

“The safety profile was similar to week 24; there were no new safety signals there at all,” he said.

The findings are of note because existing therapies for complex perianal fistulas in Crohn’s disease are often ineffective, he said, adding that fistulas occur in up to 50% of Crohn’s disease patients and that 70%-80% are complex and difficult to treat. Most are refractory to conventional anti–tumor necrosis factor therapies, and 60%-70% of patients relapse, he explained.

“If we’re honest, very few medications have been properly studied,” he said, adding that fistula patients often are excluded from industry trials.

“So [the ADMIRE CD trial] is new, design-wise, and has addressed a true medical need,” he said.

He attributed the good placebo response in this trial to the ongoing standard of care treatment in both groups, as well as to the team approach to care used in the trial. He also noted that a number of questions regarding the use of Cx601 remain to be answered, including the when the ideal retreatment time point should be, whether the treatment can be used for rectovaginal fistulas, and which patients should not receive treatment.

“So there is a lot to learn still, but I think it’s a revolutionary step forward, compared to what we have today, due to the trial design, which I think is robust, and also the encouraging outcomes,” he said.

The ADMIRE CD trial was sponsored by TiGenix SAU. Dr. Baumgart has received consulting fees and nonfinancial support from AbbVie, Biogen, and BMS.

[email protected]