TiGenix NV Announces Clinical Development of Cx611 in Early Rheumatoid Arthritis and Severe Sepsis
Jun 30 14
TiGenix NV announced that it will develop its intravenous-administered allogeneic stem cell product, Cx611, for patients suffering from early rheumatoid arthritis and for patients suffering from severe sepsis, a potentially life-threatening complication of infection. Rheumatoid arthritis is a chronic polyarticular inflammatory joint disease typically involving the small joints of the hands and feet that affects between 0.5 and 1% of adults in the developed world. Between 5 and 50 per 100,000 people develop the condition each year. After initial treatment with methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids, disease activity in a number of patients is insufficiently controlled and typically leads to treatment with a group of drugs known as biologicals, such as the TNF-alpha inhibitors. Nevertheless, lack of an adequate response in a significant portion of treated patients, safety concerns, and declining efficacy over time, requiring a substantial number of patients to periodically change drugs, indicate the need for additional therapeutic approaches. In animal models, expanded Adipose-derived Stem Cells (eASCs) have been shown to down-regulate pro-inflammatory cytokines and up-regulate regulatory T cells which modulate the immune system. In a Phase IIa study of Cx611 in refractory rheumatoid arthritis completed and presented in 2013, the safety of the product was confirmed and signs of efficacy were encouraging. Some patients treated with Cx611 entered remission after years of treatment with conventional and biological drugs. Assisted by a Steering Committee consisting of Professor Mark Genovese (Professor Immunology and Rheumatology, Stanford University, US), Professor Paul Emery (Professor of Rheumatology, University of Leeds, UK) and Professor José María Alvaro-Gracia (Head of the Biological Therapies Unit at the Hospital Universitario de La Princesa, Madrid, Spain), the principal investigator in the earlier Phase IIa study of Cx611 in refractory rheumatoid arthritis, the company is working with a group of clinical experts, including Professor Luyten (Belgium), to complete the protocol for a randomised, double-blind, comparative Phase II study to test the efficacy of Cx611 in patients exhibiting substantial disease activity of rheumatoid arthritis despite treatment with methotrexate and corticosteroids, but unexposed to a biological drug. Recruitment for the proposed study could start in the third quarter of 2015 and TiGenix would expect final results to be available by the first half of 2017. In animal models, eASCs have been shown both to decrease pro-inflammatory mediators and increase anti-inflammatory mediators, and to have anti-microbial effects. As a result of this mechanism of action, Cx611 has demonstrated efficacy in significantly reducing mortality in two animal models of sepsis. The company therefore believes that Cx611 has a potentially important role when combined with current standards of care in patients with severe sepsis. The company is working on the development plan of Cx611 in this indication with an Advisory Board of Professor Pierre-François Laterre, Dr. Bruno François (Service de Réanimation Polyvalente, Centre Hospitalier Universitaire, Limoges, France), Professor Sébastien Gibot (Service de Réanimation Médicale, Centre Hospitalier Universitaire, Nancy, France) and Professor Tom van der Poll (Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands). As well as additional animal model testing, the company will start a randomised, placebo-controlled trial to test the mechanism of action of Cx611 in healthy volunteers challenged with a bacterial endotoxin (lipopolysaccharide), a potent pro-inflammatory constituent of the outer membrane of Gram-negative bacteria, which elicits a strong inflammatory response inducing sepsis-like clinical symptoms. The company expects to complete this study by the third quarter of 2015 and follow up with a phase II trial of Cx611 as an add-on therapy to the standard of care in patients with severe sepsis.
TiGenix NV Reports Sales Results for the First Three Months Ended March 31, 2014; Provides Patient Recruitment for the European Phase III ADMIRE-CD Study of Cx601 Update
May 13 14
TiGenix NV reported sales results for the first three months ended March 31, 2014. During the first three months ending March 31, 2014, ChondroCelect sales grew 26% to EUR 1.3 million, compared to EUR 1.0 million in the same period last year.
Patient recruitment for the European Phase III ADMIRE-CD study of Cx601 in complex perianal fistulas in Crohn's disease is on track to complete by the end of 2014. This should enable study results to be obtained in the third quarter of 2015, which would allow for filing for marketing authorisation with the European Medicines Agency (EMA) in early 2016. Post-Phase IIa development plan for Cx611 to be completed shortly: With the encouraging results of the Phase IIa study of Cx611 in rheumatoid arthritis, TiGenix is working closely with international key opinion leaders on the appropriate design of follow-up studies for Cx611 in inflammatory and autoimmune disorders. TiGenix expects to finalise and announce the next steps of the development plan during the second quarter of 2014.