Cx601 appeared safe and effective for treatment of complex perianal fistulas in patients with Crohn’s disease refractory to antibiotics, immunosuppressants and/or anti-tumor necrosis factor therapy, according to research presented at the European Crohn’s and Colitis Organization’s Congress.
Mesenchymal stem cells have immunomodulatory properties, promote generation of regulatory T cells, participate in tissue-repair processes, and have shown promising results in healing perianal fistulas in patients with Crohn’s disease in recent trials, according to data presented by Julián Panés, MD, of the Hospital Clinic Barcelona in Spain.
Cx601 (TiGenix) is a suspension of expanded allogeneic adipose-derived mesenchymal stem cells (eASC) locally delivered via intra-lesional injection, which is in development for the treatment of complex perianal fistulas in Crohn’s disease patients.
The company received orphan designation for Cx601 from the European Medicines Agency in 2009, and has plans to file for European marketing approval in the first quarter of 2016, as well as plans to initiate a phase 3 trial in the U.S. in the second half of 2016, according to the company’s website.
Aiming to evaluate the safety and efficacy of Cx601 when added to current treatment in Crohn’s disease patients with perianal fistulas refractory to current medical treatments, Panés and colleagues performed a phase 3, double blind, parallel-group study of 212 patients recruited from multiple centers (mean age, 38.3 years; 54.7% men; 92.5% white). Patients had either non- or mildly active luminal Crohn’s disease and complex active perianal fistulas, and were randomly assigned to receive a single injection of 120 million eASC to all tracts or placebo.
All patients were permitted to continue their current medical treatment, and underwent fistula curettage and, if indicated, seton placement at least 2 weeks before receiving the study treatment. Combined remission at week 24, defined as closure of all treated external openings that were draining at baseline and confirmed absence of collections greater than 2 cm of the treated fistulas, served as the primary endpoint.
In the intention-to-treat cohort, 49.5% of patients treated with Cx601 achieved the primary endpoint compared with 34.3% of those who received placebo (P = .024). In the safety cohort (n = 205), 51.5% of Cx601-treated patients vs. 35.3% of placebo-treated patients achieved the primary endpoint (P = .019). Numerically more patients in both cohorts who were treated with Cx601 achieved clinical remission, and significantly more achieved response in the safety population (P = .039).
The distributions of time to clinical remission and response differed between groups (P < .05), with an estimated twofold shorter time to clinical remission (6.7 vs. 14.6 weeks) and response (6.3 vs. 11.7 weeks) in the Cx601 group compared with placebo.
The treatment was also well tolerated, and treatment related adverse events occurred in 17.5% of the Cx601 group compared with 29.4% of the placebo group.
Cx601 showed significantly greater efficacy compared with placebo in terms of the primary endpoint and showed an acceptable safety and tolerability profile, Panés concluded. – by Adam Leitenberger
Panés J, et al. Abstract OP001. Presented at: ECCO Congress; March 16-19, 2016. Amsterdam.
Disclosure: Panés reports consulting fees, speaking fees, honoraria, and/or other fees and support from Abbott, Boehringer Ingelheim, Genentech-Roche, MSD, Shire, Tillotts, Tigenics, Topivert, Pfizer, Galapagos and Takeda. Please see the ECCO disclosures database for all other researchers’ relevant financial disclosures.