Crohn’s disease and perianal fistulas
Crohn’s disease is a chronic inflammatory disease of the intestine. A complication of the disease is complex perianal fistulas. A perianal fistula is an abnormal connection between the perianal space and outside skin surface which causes a significant negative impact on quality of life. A fistula is considered to be complex when its treatment involves a high risk of causing loss of anal continence, the fistulous tract crosses more than 30% of external sphincter, several tracts are found, it is recurrent, or when the patient has incontinence, local irritation, or Crohn’s disease. Current treatment for complex fistula in patients with Crohn’s disease is marked by poor efficacy and high costs. Patients with complex fistula but no inflammatory disease require surgery, with its attendant risk of faecal incontinence.
Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASC) locally injected. Cx601 is an investigational agent being developed for the treatment of complex perianal fistulas in Crohn’s disease patients that failed conventional therapy including antibiotics, immunosuppressant, or anti-TNF therapy. Crohn’s disease is a chronic inflammatory disease of the intestine and patients can suffer from complex perianal fistulas for which there is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognizing the debilitating nature of the disease and the lack of treatment options.
On July 4, 2016 TiGenix entered into a licensing agreement with Takeda, a pharmaceutical company leader in gastroenterology, whereby Takeda acquired an exclusive right to commercialize Cx601 for complex perianal fistulas in Crohn’s patients outside of the U.S.
Cx601 has met the primary end-point in the Phase III ADMIRE-CD study in Crohn’s disease patients with complex perianal fistula, a randomized, double-blind, placebo-controlled trial run in Europe and Israel and designed to comply with the requirements laid down by the EMA.
The study’s primary endpoint was combined remission, defined as clinical assessment at week 24 of closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections >2cm confirmed by MRI. In the ITT population (n=212), Cx601 achieved statistically significant superiority (p=0.024) on the primary endpoint with 50% combined remission at week 24 compared to 34% in the placebo arm. Efficacy results were robust and consistent across all statistical populations. Treatment emergent adverse events (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and placebo arms. The 24-weeks results have been published by The Lancet, one of the most highly regarded and well-known medical journals in the world. The Phase III study has completed a follow-up analysis at 52 weeks confirming its sustained efficacy and safety profile. Top line follow-up data showed that in the ITT population Cx601 achieved statistical superiority (p=0.012) with 54% combined remission at week 52 compared to 37% in the placebo arm. In addition, after fifty-two weeks, 75.0% of patients treated with Cx601 who were in combined remission at week twenty-four did not relapse, compared to 55.9% for patients in the placebo arm who were in combined remission at week twenty-four. Based on the positive 24-weeks Phase III study results, TiGenix has submitted a Marketing Authorization Application to the EMA in early 2016. TiGenix is preparing to develop Cx601 in the U.S. after having reached an agreement with the FDA through a special protocol assessment procedure (SPA) in 2015.
Cx601 has been designated as an orphan drug by the EMA and the SwissMedic, in Switzerland. Based on the Phase II clinical trial report, the Committee for Medicinal Products for Human Use (CHMP) of the EMA stated that it considered the presented preclinical and clinical data package to be sufficient for the submission of a Market Authorisation Application (MAA). The CHMP also indicated that a single Phase III study would be sufficient to support an MAA in terms of efficacy.
Based on industry reports, TiGenix estimates the treatment of complex perianal fistulas in Crohn's disease patients to represent a market size range of approximately $3.5 billion to $5.9 billion for Europe and the United States combined.
Soft loan to support development of Cx601
In October 2011, TiGenix, through its wholly-owned subsidiary Cellerix SA, obtained a EUR 4.95 million soft loan from the ‘Madrid Network’ to finance the Cx601 Phase III study. The soft loan covers a substantial part of the development costs of Cx601. ‘Madrid Network’ is an organisation within the Autonomous Region of Madrid which helps companies to grow through high-technology innovation. The programme is funded by The Secretary of State for Research, Development and Innovation (Ministry of Economy and Competitiveness) within the framework of the INNTEGRA plan.