SangStat Medical Corp. continued its run of good news Monday withPhase III results showing Thymoglobulin not only was equivalent tothe standard therapy in reversing acute graft rejection but performedbetter than an existing treatment.
Thymoglobulin, a rabbit anti-thymocyte polyclonal antibody,successfully reversed acute rejection following kidney transplantationin 88 percent of 82 evaluable patients. The standard therapy, a horseantibody called Atgam, was successful in 76 percent of 80 patients.
The pasteurized product is globulin therapy that destroys T cells,which are generated by the organ recipients and cause rejection ofdonor kidneys. The polyclonal antibodies are derived from rabbitsinjected with human thymus cells.
"For us to show a double-digit difference in favor of Thymoglobulinis a great result because it goes beyond what the aim of the trial wasand is what we believe we need from the FDA to get the productlicense application [PLA] filed and reviewed," Philippe Pouletty,chairman and CEO of SangStat, told BioWorld Today.
Patients in the double-blind study were randomized to receive 1.5mg/kg per day of Thymoglobulin or 15 mg/kg per day of Atgam forseven to 14 days; then they were followed for three months. Patientsalso were stratified according to degree of rejection severity.
The primary endpoint in the pivotal comparative trial was post-therapy return of serum creatinine level to, or below, baseline.Thymoglobulin and Atgam were deemed equivalent in the secondaryendpoints of graft survival at 30 days, creatinine to baseline ratio at30 days, and histological improvement in post-therapy biopsies. Nosafety differences were noted.
Pouletty said SangStat, of Menlo Park, Calif., plans to file a PLA bythe end of the year based on the trial results. Last week the companysaid pivotal trials of its cyclosporine formulation demonstratedbioequivalence to the marketed version of the immunosuppressivedrug sold by Sandoz Ltd., of Basel, Switzerland. An applicationseeking approval of that drug also is expected by year's end, he said.
SangStat's stock (NASDAQ:SANG), which gained $2.13 Friday inanticipation of the Thymoglobulin news, fell 63 cents Monday toclose at $29.50. The stock was at $10 at the beginning of the year.
Mary Ann Gray, an analyst at new York-based Dillon, Read & Co.Inc., on Friday raised her 12-18 month price target on SangStat from$25-$30 to $35-$40. "SangStat continues to meet or beat ourexpectations on all fronts and has a string of news continuing wellinto 1997," Gray wrote.
SangStat acquired exclusive rights in 1993 to develop and marketThymoglobulin in North America from Pasteur Merieux Serums etVaccins, of Lyon, France. The product already is approved in 39countries and been used in more than 30,000 patients.
Another approved product for this indication is Raritan, N.J.-basedOrtho Biotech Inc.'s Orthoclone OKT3, a murine monoclonalantibody.
Pouletty said SangStat's product, in addition to performing better inthe head-to-head trial with Kalamazoo, Mich.-based Pharmacia andUpjohn's Atgam, has such a long track record that he expects manyphysicians will opt to use Thymoglobulin. More than 50 peer-reviewed articles have been published on the drug, he said.
Atgam costs about $850 per day and OKT3 about $500 per day,Pouletty said. "SangStat's strategy will be to price Thymoglobulincompetitively but we have not decided on the end-use price," he said.
SangStat is fairly unique in the biotechnology circles for havingresults from two pivotal trials within a week: "Thymoglobulin forrejection and cyclosporine for prevention of rejection can form aplatform on which we can build a disease management franchise,"Pouletty said.
The company has 10 other products to address the pre-transplant,acute care and chronic phases of transplantation. SangStat last monthset up a pharmacy operation that will serve as a distribution channelfor the transplant market, as well as a conduit among patients andphysicians.
An application is on file seeking approval of Thymoglobulin inCanada, where it already is being used in a compassionate-usesetting. SangStat hopes to have results from a pivotal bioequivalencetrial of azathioprine for chronic immunosuppressive therapy in thefirst quarter of 1997, and is in Phase II trials with Allotrap 2702 topromote graft acceptance following transplantation. The company hasmonitoring products on the market and in development, an organpreservation solution, and a drug candidate in early development forxenotransplantation.
Additional results from the Thymoglobulin trial will be presented at asymposium in New Orleans on Nov. 2 at the Annual ScientificMeeting of the National Kidney Foundation. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.