Ontaril^® (Cx401) is a medicine based on expanded mesenchymal stem cells obtained from adipose tissue (eASCs). This product belongs to a new generation of cell therapies:

• It is the first eASC-based medicine in the world to be investigated in a clinical trial.
• It is a natural medicine with the capacity to activate the body’s own physiological repair mechanisms through its ability to interact with affected tissue.
• Ongoing clinical trials show that Ontaril^® has great therapeutic potential based on its anti-inflammatory properties and its ability to induce healing and regulate the immune system.

Ontaril^® is an injectable suspension that contains stem cells that are isolated from a sample of the patient’s adipose tissue obtained by a minor liposuction procedure and subsequently expanded.

Ontaril^® is currently under evaluation in several clinical trials for two indications:

• Treatment of complex perianal fistulas of cryptoglandular origin (patients without inflammatory bowel disease).
• Treatment of complex perianal fistulas associated with Crohn’s disease.

A perianal fistula is an abnormal communication between the perianal space and the outer surface of the skin. Fistulas are considered complex when treatment is associated with a high risk of causing loss of anal continence, the fistulous track covers more than 30% of the external sphincter (high transsphincteric, suprasphincteric and extrasphincteric), several tracks are present, the fistula is recurrent or the patient suffers from incontinence, local irritation or Crohn’s disease.

Treatment of complex fistulas in Crohn’s disease patients has low success rates and is costly. In the case of patients with complex fistulas but without inflammatory disease, treatment is usually surgical and brings with it a risk of fecal incontinence.

Treatment of complex fistulas in Crohn’s disease patients has low success rates and is costly. In the case of patients with complex fistulas but without inflammatory disease, treatment is usually surgical and brings with it a risk of fecal incontinence.

Ontaril^® acts to reduce inflammation in the fistula in a controlled fashion, responding to environmental stimuli and promoting an appropriate homeostasis through release of anti-inflammatory factors which in turn facilitate fistula closure.

Ontaril^® has been designated an Orphan Drug by the European Medicines Agency.

Advantages of cell therapy with eASCs

Cell therapy with eASCs has a series of advantages when compared with traditional treatments and newer biologic therapies:

• It is based on a multiple mechanism of action that responds to the environment in which the cells are used.
• It takes advantage of the intrinsic therapeutic properties of the medicine (live cells).
• The cells used are a natural component of the body itself and so the medicine should potentially be safer with fewer side effects.

Fat as a source of stem cells

Ontaril^® can be obtained from body fat. Fat has a number of advantages over other widely used sources of stem cells:

• It is rich in stem cells (between 100 and 1000 times more cells are present than in other tissues often used, such as bone marrow).
• Fat is present in all individuals.
• It is readily accessible. The tissue from liposuction procedures is considered a waste material that is currently not utilized.
• Fat is readily regenerated.

Results of previous clinical trials

A Phase I study was undertaken to evaluate the feasibility and safety of Ontaril^®, and the findings confirmed the potential of the product for treating fistulas in Crohn’s disease patients. The main conclusion of the study was that the product was safe and that 75% of the patients responded, with complete closure and healing of the fistulas eight weeks after treatment. The study was the first clinical trial in the world to be carried out with stem cells derived from adipose tissue, and it showed the efficacy of the product.

Further information:

García-Olmo D, García-Arranz M, García LG, Cuellar ES, Blanco IF, Prianes LA, Montes JA, Pinto FL, Marcos DH, García-Sancho L. Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy. Int J Colorectal Dis. 2003 Sep;18(5):451-4. [Medline]

García-Olmo, D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A Phase I Clinical Trial of the Treatment of Crohn’s Fistula by Adipose Mesenchymal Stem Cell Transplantation. Dis Colon Rectum 2005; 48: 1416–1423.[Medline]

A subsequent Phase II study with 50 patients confirmed the efficacy and safety of Ontaril^®. The primary objective of this study was to clinically and objectively assess complete closure and healing of the fistula. A response rate of 71% was found in the acute phase in patients with and without Crohn's disease. The results of this study were presented at the Digestive Disease Week international congress in Washington in May 2007 and are currently in the process of being published in full.

Further information:

www.clinicaltrials.gov

García-Olmo D, Herreros D, Pascual I, Pascual J, Del Valle E, Zorrilla J, De La Quintana P, García-Arranz M, GonzáLez M, Alemany M, Fernández G, Portero I, Pascual M. Expanded Adipose-derived Stem Cells (Cx401) for the Treatment of Complex Perianal Fistula. A Phase II Clinical Trial. Abstract 492.[PDF]

FATT I (Fistula Advanced Therapy Trial I)

Cellerix is conducting a multicenter Phase III clinical trial in Europe with 207 patients to evaluate the efficacy and safety of treatment with Ontaril^® in complex perianal fistulas in patients without inflammatory bowel disease.

Further information:

www.clinicaltrials.gov