Protein Design Labs Inc. reversed a steep decline, rising 8 percentWednesday after dropping sharply two days earlier on Phase II/IIItrial data from its partner, Hoffmann-La Roche Inc., showing thatZenapax, a humanized antibody targeting T cells, failed to preventgraft versus host disease (GvHD) in bone marrow transplant patients.
Protein Design's stock (NASDAQ:PDLI) ended the day up $1.12 at$15. Hoffmann-La Roche, of Nutley, N.J., and Protein Design, ofMountain View, Calif., released results of the Phase II/III study lateFriday after the market closed. Protein Design felt the effectsMonday, the day before the July Fourth holiday, when its stockplummeted $6.87, from $20.75 to $13.87, a 33 percent drop.
Matthew Geller, an analyst with Oppenheimer & Co., in New York,described the plunge in stock price as "a gross overreaction" by themarket.
Darien Wilson, Hoffmann-La Roche spokeswoman, said thecompany, which licensed worldwide rights to Zenapax from ProteinDesign, has not lost confidence in the humanized Anti-Tac antibody.
She said Hoffmann-La Roche, a subsidiary of Switzerland-basedRoche Holding Ltd., is continuing two Phase III trials of the drug forthe prevention of kidney transplant rejection. Those studies,involving 250 patients, are expected to be complete by mid-1996.
Peter Dworkin, Protein Design spokesman, said Zenapax is one offour Protein Design antibodies in clinical trials and is the only onelicensed out on a worldwide basis.
Although an earlier Phase I trial suggested Zenapax could reduce theT cell mediated response that leads to GvHD, Dworkin said the PhaseII/III study "suggests that other mechanisms" are involved in thedisease.
GvHD occurs when T cells from the donor's bone marrow recognizethe transplant recipient's tissues as foreign and initiate an immuneattack.
Protein Design's Zenapax, which is a mouse monoclonal antibodythat has been modified for use in humans, targets the interleukin-2receptor on activated T cells, blocking it and preventing theirproliferation. In kidney transplant patients, the drug is aimed atinhibiting the recipient's T cell response to a donor organ.
A positive aspect of the GvHD trial, Dworkin observed, was the lackof human anti-mouse antibody (HAMA) response in patients. Onlyone of 140 patients who received Zenapax experienced a HAMAresponse, which occurs when the transplant recipient's immunesystem destroys the antibodies and their effectiveness.
Geller said Zenapax is the first humanized antibody tested in large-scale clinical trials to demonstrate it can overcome the problem ofHAMA responses. In addition, Geller noted the GvHD studiesshowed the drug was safe, with only two serious adverse events, andthey indicated Zenapax delayed the disease.
"This was actually a Phase II trial," Geller said, "not a Phase II/III."
In a Phase I study for prevention of kidney transplant rejection,Geller noted that Zenapax demonstrated some effectiveness. "That'svery unusual for a Phase I," he said. "This drug is blocking T cells."
Hoffmann-La Roche's Phase II/III GvHD studies involved 210patients, all of whom received the GvHD standard therapy(cyclosporin and methatrexate). They were divided into three groups;those getting a placebo and those receiving Zenapax at one of twodoses. The primary endpoint was disease prevention as measured bypresence of GvHD at 100 days after the bone marrow transplant.
GvHD, a deadly disease, kills 40 percent of those affected in 100days and 60 percent in a year.
Wilson said details of the GvHD trials were not available. She said adecision on whether to continue development of Zenapax for GvHDwill not be made until after a full analysis of the data. She added thatGvHD was the first indication pursued by Hoffmann-La Roche forthe drug and that in "early studies it appeared it would be effective."
In addition to the Phase III trials of Zenapax for prevention of kidneytransplant rejection, Hoffmann-La Roche is conducting preclinicalstudies of the antibody for autoimmune diseases. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.