By Randall Osborne
MedImmune Inc. and BioTransplant Inc. reported positive data from a 20-patient Phase II trial of BTI-322, a murine monoclonal antibody for graft-versus-host disease (GvHD) in bone marrow transplant patients, and the companies are enrolling patients in a Phase II study of the humanized version, known as MEDI-507.
"There's no data yet to suggest [MEDI-507] is better, and it's an interesting question in a person who is immune suppressed," said Mark Kaufmann, spokesman for Gaithersburg, Md.-based MedImmune.
Results from the BTI-322 trial, though, are clearly positive. Of the 20 patients, 55 percent showed a complete response or a reduction in grade of the disease. All patients in the study received allogeneic (non-self donated) bone marrow or stem cell transplants.
Of the 11 patients improving, six had complete resolution. All 20 received a single daily dose of BTI-322, along with a standard regimen of immunosuppressive drugs. Aside from mild to moderate first dose reactions, all tolerated the drug well, but the majority relapsed when it was stopped.
"Whether that means they won't relapse if we continue to give the drug, we don't know, because we haven't done the study," Kaufmann said.
Elliot Lebowitz, president and CEO of Charlestown, Mass.-based BioTransplant, said switching to the humanized antibody is "a serious deal, because a rodent antibody [such as BTI-322] can only be administered for a couple of weeks." Using the humanized antibody for a longer period will provide a better indication of its potential.
Patients need all the help they can get. "They're very sick," Lebowitz said. "The endpoint [in trials] is basically improvement in the stage of the disease at 100 days. These [patients in the study] were on all the best therapies and not responding, but they responded to BTI-322. That's the good news."
GvHD, in which white blood cells from donor bone marrow attack the tissue of the recipient, is an often fatal outcome of bone marrow transplants. In cases refractory to steroid treatment, the mortality rate is estimated at over 70 percent. BTI-322 and MEDI-507 work by binding to the CD2 antigen receptor on T cells and natural killer cells, suppressing their immune response.
BioTransplant exclusively licensed BTI-322 and MEDI-507 to MedImmune as anti-rejection drugs, with MEDI-507 potentially to be used to treat autoimmune diseases. The companies began collaborating in 1995. (See BioWorld Today, Oct. 13, 1995, p. 1.)
The deal was said to be worth up to $14 million. Of that, $4 million has been realized, Lebowitz said.
Kaufmann told BioWorld Today a Phase I safety trial with MEDI-507 showed it "seems to be acting in the same fashion as BTI-322." If the Phase II yields positive results, a Phase III trial would be conducted next year.
"Having the safety data behind us for MEDI-507 hopefully will allow us to get into some other indications, such as psoriasis," he added. Lebowitz said the companies' strategy is to use psoriasis as a marker for other autoimmune diseases. "We have discovered in vitro that this antibody has remarkably unusual properties," he said.
Also this month, BioTransplant received clearance from the FDA for its investigational new drug application to begin a Phase I/II study to evaluate the AlloMune System, which allows transplants of mismatched kidneys without the use of immunosuppressive drugs, and involves mixing bone marrow from the patient and a donor to create chimeric bone marrow.
MedImmune won FDA approval last month for Synagis, its monoclonal antibody to prevent respiratory syncytial virus in children and infants. (See BioWorld Today, June 22, 1998, p. 1.)
BioTransplant's stock (NASDAQ:BTRN) closed Thursday at $3.50, up $0.25. MedImmune's shares (NASDAQ:MEDI) ended the day at $64.25, down $0.375. *