TP-10 (AVANT Immunotherapeutics).

AVANT Immunotherapeutics is developing TP-10, a recombinant soluble complement receptor type 1 (sCR1), for the potential treatment of reperfusion injury (following surgery, ischemic disease and organ transplantation), organ rejection, acute inflammatory injury to the lungs and autoimmune diseases [348669]. TP-10 has been awarded Orphan Drug status from the FDA for the prevention and reduction of adult respiratory distress syndrome (ARDS) and as a treatment for infants undergoing cardiac surgery [180849], [359588]. A placebo-controlled phase II trial, conducted at approximately 30 sites in the US and involving approximately 600 adult patients undergoing cardiac surgery utilizing cardiopulmonary bypass, was initiated in November 2000. This safety and efficacy study was designed to assess the ability of TP-10 to mitigate the injury to the heart, brain and other organs that occurs when patients are placed on cardiopulmonary bypass circuits, thus potentially improving postoperative outcomes [391437]. In September 2000, the company was planning a double-blind, placebo controlled phase IIb trial in infants undergoing cardiac surgery; AVANT expected to initiated in 30 infants in January 2001 [395086]. The data from this trial will enable the company to further define its clinical endpoints before inititating a pivotal phase III trial in 2001 [382529]. A phase I/II trial of TP-10 involving 15 infants, under 12 months of age, undergoing cardiac surgery for congenital heart defects was initiated by the company in September 1999. The trial will evaluate the ability of TP-10 to mitigate the injury to the heart and other organs when patients are placed on cardiopulmonary bypass circuits [340602]. Enrollment was complete by January 2000 [352458]. Phase I safety trials of TP-10, including studies in adult patients at risk for adult respiratory distress syndrome (ARDS), adult patients with first-time myocardial infarction (heart attack), and pediatric patients undergoing cardiac surgery demonstrated that TP-10 is well tolerated. However, after completion, in December 1997, of a phase IIa trial in nine patients with ARDS, AVANT decided to cease development for this indication. TP-10 was licensed to Novartis AG for use in xeno- and allotransplantation in July 1999. Extensive animal studies have shown TP-10 to have potential in a wide variety of complement-mediated conditions, including organ transplantation, multiple sclerosis, rheumatoid arthritis and lupus [238093]. Early work demonstrated favorable results in animal models of reperfusion injury [180849] and hyperacute xenograft rejection in guinea pig to rat and pig to primate organ transplants [191552]. AVANT has received Notices of Allowance (July 1998) from the USPTO for three separate patent applications covering pharmaceutical compositions of TP-10, methods of purification and methods of certain TP-10 glycoforms for treating diseases or disorders resulting from inappropriate complement activation [291776]. In January 1999, the company was awarded US-05856297 which covers pharmaceutical compositions of TP-10. US-05856300 was also awarded covering compositions and methods of producing the drug [312267].