Positive results were reported in January 2010 for a GenVec-sponsored trial in which researchers injected gene encoding for tumor necrosis factor-alpha (TNF-alpha) directly into tumors. This led to pathologic complete responses in one-third of the 24 esophageal cancer patients; the median survival was four years. Patients who received the three lowest does of TNF had a five-year survival rate. The therapy resulted in nodal conversion and down-staging in the majority of patients, most of whom had surgical resection following chemoradiation and the intratumoral injections of TNF, said the researchers. Kenneth J. Chang, MD, of the University of California Irvine reported at the Gastrointestinal Cancers Symposium that the results were encouraging and warrant further evaluation. However, another investigator in the multicenter study said the regimen is complicated and time-consuming and that the trial was stopped because of treatment-related deaths that had not been fully explained. Regardless, the therapy has received FDA fast-track status for evaluation in the treatment of pancreatic cancer.
Aeolus Pharmaceuticals announced in October 2009 that recent preclinical studies have shown that its AEOL 10150 therapeutic can effectively increase regeneration of gastrointestinal stem cells, reduce the severity and duration of diarrhea and improve survival when administered at 24 hours after doses of total-body irradiation that produce lethal GI syndrome. The studies are being conducted by contract research organization Epistem, a subcontractor of the University of Maryland. The compound is being studied as part of the National Institutes of Health’s program for the screening of novel agents for bio-defense applications, such as a terrorist nuclear act. At this time, there are no therapeutic therapies FDA approved for this application.
Cellerix SA is developing cell therapy injectables for patients with automimmune disorders such as Crohn’s disease. Ontaril and Cx601 are currently in clinical trials for treating perianal fistulas in these patients.
In December 2009, Athersys entered into an agreement with Pfizer to develop and commercialize MultiStem for the treatment of inflammatory bowel disease. Under terms of the agreement, Athersys received a cash payment of $6 million from Pfizer as well as research funding and support during the initial phase of the collaboration. Milestone payment of up to $105 million may also e paid, depending on the successful achievement of certain development, regulatory, and commercial milestones. Pfizer will assume development, regulatory and commercialization and will pay Athersys tiered royalties on worldwide sales of MultiStem IBD products. Athersys is also investigating the use of MultiStem for treatment of obesity.
Selected competitors in the field of tissue engineering and cell-based therapies for gastrointestinal applications are shown in the exhibit below.
Key Competitors in Tissue Engineering and Cell Therapies for Gastrointestinal Applications
|CNS surgery:||* Adhesive agent in CNS tissue surgery. CNS tissue cannot be sutured. Fibrin glue is almost equivalent to microsurgical suture. Fibrin glue works as a sealant but not a nerve barrier.|
|* Repair of dural defects.|
|Eye surgery:||* Conjunctival closure in strabismus.|
|* Wound closure in glaucoma.|
|* Lower blepharoplasties (for lower eyelids).|
|ENT surgery:||* Myringoplasty in large persistent tympanic membrane perforation.|
|* Repair of laryngotracheal separation with cricoidectomy.|
|* Narrowing of nasal fossa in atrophic rhinitis.|
|Oral and dental surgery:||* Local hemostatic measures in patients with bleeding disorders and patients on anticoagulants.|
|* Sealing of oro-antral fistula.|
|Head and neck:||* Parotidectomy closure.|
|* Axillary dissection in carcinoma of the breast. Reduces adhesion, bleeding and serous drainage with earlier drain.|
|* Prevention of mastectomy seroma.|
|Cardiovascular thoracic surgery:||* Reduced postoperative bleeding and intrapericardial adhesion.|
|* In cardiothoracic surgery using fibrin glue significantly reduced postoperative bleeding.|
|Chest surgery:||* Sealing of prolonged air leak after thoracotomy in lung cancer.|
|* Bronchopleural fistula.|
|* Percutaneous lung biopsy.|
|Vascular surgery:||* Microvascular anastomosis: Suture may induce vascular narrowing, foreign body reaction, intravascular thrombosis but are less common in those with fibrin glue application.|
|Gastrointestinal surgery:||* Gastrointestinal sutureless anastomosis-stent.|
|* Esophagus perforation.|
|* Esophago-jejunal anastomosis.|
|* Recurrent tracheo-esophageal fistula.|
|* Upper gastrointestinal tract fistula: Endoscopic obliteration.|
|* Cholecysto-jejunostomy (sutureless) using absorbable intraluminal stent.|
|Liver surgery:||* Liver resection in benign and malignant diseases.|
|Uro/Gynecological system:||* Colpofixation in stress urinary incontinent.|
|* Intractable transplant-ureteral fistula.|
|* Transvaginal colpo-urethropexy.|
|Gynecological surgery:||* Recto-vaginal and ano-rectal fistula.|
|* Anastomosis of the fallopian tube in animals.|
|Bone & orthopedic surgery:||* Joint replacement.|
|* Brachial plexus injury repair.|
|Plastic surgery:||* Face lift procedure. Fibrin glue reduces major hematomas and ecchymoses.|
|* Musculo facial plastic surgery, dorsal hand burns, infected skin graft.|
|* Decrease wound contraction in skin graft.|
Source: MedMarket Diligence, LLC; Report #S520, "Tissue Engineering, Cell Therapy and Transplantation Worldwide."