Two clinical studies, a Phase III by Xoma Corp. andPhase II by Applied Immune Sciences Inc., testeddifferent approaches for eliminating graft-versus-host-disease (GvHD) in allogenic bone marrow transplantswith varying results.
About 18,000 bone marrow transplants are performedworldwide each year in treatments for blood-bornecancers and genetic blood disorders and an estimated10,000 involve allogenic bone marrow. However, the riskof GvHD precludes many more patients from gettingtransplants, said Tom Okarma, chief scientist for AppliedImmune Sciences.
"Two out of every three leukemia patients can't find amatched donor and cannot get a transplant because thereare no suitable donors," he said, adding that allogenicbone marrow transplants can work as well as matchedones, except for the GvHD side effects.
GvHD occurs when T cells in the donor bone marrowrecognize the recipient's tissues as foreign and initiate animmune system attack, which causes rejection of thetransplant. Typically, 50 percent of allogenic bonemarrow recipients develop acute GvHD and half of themdie.
Xoma Corp., of Berkeley, Calif., said its Phase III trial ofCD5 Plus for acute GvHD did not show statisticalsignificance in its primary clinical endpoint. But Xomaspokesman, David Ringler, said the data revealed enoughactivity to warrant continued analysis before deciding bythe end of this year whether to file a product licenseapplication with the FDA. Xoma's stock(NASDAQ:XOMA) closed Tuesday at $3.31, down 56cents.
Applied Immune Sciences, of Santa Clara, Calif.,reported more successful results from its Phase II study,which used a preventive approach to battling the disease.
Both companies presented data from their studiesTuesday at the 36th annual meeting of the AmericanSociety of Hematology in Nashville.
Xoma's three-year Phase III trials involved 243 bonemarrow recipients suffering from acute GvHD. Theparticipants, who were not receiving chemotherapy, weregiven either a combination of CD5 Plus and steroidaltherapy, which is a common treatment for GvHD, orsteroid treatments and a placebo. Following treatmentsthe patients were analyzed periodically to determine ifGvHD was in remission.
Ringler said CD5 Plus, a monoclonal antibody conjugatedirected against CD5 T cells, revealed statisticalsignificance in causing remission of GvHD at 22 daysafter the treatment, 29 days and 36 days. But at 43 days,no statistical significance was found between the CD5Plus and placebo groups in number of patients withGvHD. The study's primary endpoint was no evidence ofGvHD at 43 days.
Applied Immune Sciences, in its Phase II study, used thecompany's AIS CELLector CD5/CD8 device to depleteCD5 and CD8 T cells from donor bone marrow before itwas transplanted to thwart the onset of GvHD. In additionto the specific T cell depletion process, the donors' bonemarrow was treated with drugs currently used to combatGvHD.
Data from the trial revealed that only two of 15 patients,or 13 percent, developed acute GvHD. The results alsoshowed minimal depletion of CD34+ cells, which areneeded for revitalizing the blood and immune systems.
Jackie Cossmon, spokeswoman for Applied ImmuneSciences, said the company hopes to begin a Phase IIItrial involving about 140 patients in early 1995. Theprimary end point, she said, will be reduction of GvHD.The company's stock (NASDAQ:AISX) was down 25cents Tuesday to close at $5.50.
In the Xoma trials, Ringler said investigators willcontinue analyzing patients up to 100 days after the initialtreatments.
"If we felt the data showed CD5 Plus didn't work wewouldn't continue the analysis," he said. Xoma iscollaborating with Johnson & Johnson, of NewBrunswick, N.J., on development of CD5 Plus.
Ringler added, "We've disclosed publicly thatcommercialization of CD5 Plus for GvHD is not ofeconomic significance to the company [because of thesize of the market]."
He said Xoma is focused primarily on development ofNeuprex, a recombinant bacterial permeability-increasingprotein (BPI) for infections, such as severe sepsis andshock related to hemorrhages, as well as for use incombination with antibiotics to enhance their effects.Ringler said the company expects to begin Phase II trialsnext year with BPI. n
-- Charles Craig
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