Washington Editor

Protein Design Labs Inc. decided against further development of Zamyl as an acute myeloid leukemia treatment on news that its Phase III trial failed to show statistical significance.

The results were disclosed at the American Society of Clinical Oncology meeting in Orlando, Fla., Sunday.

Company officials, however, expect to present positive data today from a Phase I/II study of a Crohn's disease antibody at the Digestive Disease Week meeting in San Francisco. The product is referred to as the Smart Anti-Gamma Interferon Antibody, and already is the subject of a Phase II randomized, double-blind, placebo-controlled study in 175 patients at 25 sites in North America and Europe.

Unfortunately, though, the future doesn't look so bright for use of Zamyl in myeloid leukemia patients who failed chemotherapy or relapsed following chemotherapy. Final analysis of the Phase III trial indicated that the overall response rate in patients who received Zamyl in combination with chemotherapy was 36 percent (n=94), and 28 percent in patients who received chemotherapy alone (p=0.28; n=97), when all evaluable patients were analyzed on an intent-to-treat basis, the company said.

Also, PDL reported that in the Zamyl-chemotherapy group, 29 percent of participants achieved a complete response (n=94) and in the chemotherapy group, 23 percent achieved a complete response (p=0.41; n=97).

Jim Goff, PDL's spokesman, referred BioWorld Today to a prepared statement released by Douglas Ebersole, the company's acting CEO, which said, "Based on this analysis, we do not plan to seek meetings with regulatory authorities or to consider filing a biologics license application for Zamyl at this time. Nevertheless, Zamyl has continued to demonstrate positive trends and possible therapeutic activity, and we expect to explore partnering opportunities that would allow continued development of this novel, humanized antibody."

Even though PDL is not studying Zamyl in other indications, Goff said, the drug is the subject of several physician-sponsored investigational new drug applications and physician-sponsored trials, "but we do not currently have plans to initiate further trials sponsored by Protein Design Labs."

Zamyl is a humanized antibody that binds to the CD33 antigen on myeloid leukemia cells. It is the humanized version of the murine M195 monoclonal antibody.

In December, PDL said while it had missed the primary endpoint in the Zamyl Phase III trial, company officials believed they had sufficient data for the BLA. (The primary endpoint was complete response within 70 days.)

An initial review of the data indicated that Zamyl and chemotherapy together generated an overall response rate of 43 percent, compared to a 26 response rate in patients receiving chemotherapy alone (p=0.015). (See BioWorld Today, Dec. 10, 2001.)

PDL on Sunday said the differences in preliminary data and final analysis are related to additional data received on a number of patients, such as additional blood cell counts and transfusion information and to the reclassification of a number of patients by a panel of hematologists and oncologists that reviewed the data.

Despite the negative news associated with Zamyl, Goff said PDL still possesses a healthy pipeline that includes seven proprietary antibodies in development.

Among them is Remitogen, a Phase II product being studied for non-Hodgkin's B-cell lymphoma.

Goff said the dosing regimen of Remitogen was modified late last year upon news that only one patient had partially responded to treatment. At that point in the study, 25 of the 40 enrolled patients had completed the study.

Goff acknowledged the Street did not respond favorably to the Remitogen setback. However, the reaction was completely different in late March when PDL said it would abandon further development of Zenapax as a maintenance agent for psoriasis following poor preliminary Phase II results. (See BioWorld Today, March 22, 2002.)

PDL's stock shot up 21.8 percent, or $3.28, to close at $18.30 after that disclosure. The company said it is studying Zenapax in other indications. Since 1997, Zenapax has been marketed for prevention of kidney transplant rejection by PDL partner F. Hoffmann-La Roche Ltd., of Basel, Switzerland.

Jennifer Chao, a senior biotech analyst with Leerink Swann & Co. in New York, told BioWorld Today that PDL is experiencing growing pains. "They are at a very critical juncture in their corporate development. It's tough to make the transition from a technology-based platform to a therapeutic-based platform. Unfortunately, we've seen some disappointments early on that have led investors to question whether the company has the wherewithal to develop clinical products."

Aside from the product issues, Chao pointed out that management troubles also may create some concern for investors.

In early May, CEO Laurence Jay Korn and the president of research and development, David Levitt, both resigned.

"They need to get their house in order. Clearly, there is a senior management void," she said. "They need to figure out where their strengths are. With a treasure chest of $640 million, they should aggressively start prospecting which late-stage molecules they have the wherewithal to take forward."

Goff said Korn's decision to step down as CEO was the result of a "mutually agreed upon decision with the board of directors based on the evolution of the company. We want leadership that can help us make the transition from a development company to a company that commercializes and markets products."

Korn retains his role as chairman of the board. Levitt did not detail his reasons for resigning, Goff said.

PDL's stock (NASDAQ:PDLI) gained 1 cent Monday to close at $12.28.