Experimental Drugs for HBV Infection1

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Ostavir (human anti-hepatitis B antibody), (Protein Design Labs)



Protein Design Labs Announces Phase IIa Clinical Trial of Ostavir Human Anti-Hepatitis B Antibody

Mountain View, California



Protein Design Labs, Inc. (PDL) (Nasdaq: PDLI) announced today that a Phase IIa clinical trial has begun in Europe with Ostavir(TM), PDL's human anti-hepatitis B antibody (also known as OST 577) in patients with chronic hepatitis B (CHB).



The purpose of the trial is to evaluate the safety, pharmacokinetics and activity of Ostavir when administered to CHB patients who also are being treated with the antiviral nucleoside analog lamivudine. Patients receive lamivudine until their serum hepatitis B viral DNA reaches levels undetectable by a hybridization assay, and are then administered six doses of Ostavir over two weeks while continuing on lamivudine therapy.



"This clinical trial is designed to test the hypothesis that Ostavir can be safely administered to patients with CHB infections when viral replication is inhibited by lamivudine and to test whether the antibody reduces circulating virus levels in this setting as detected by PCR assay and the presence of hepatitis B surface antigen," said Daniel J. Levitt, M.D., Ph.D., Senior Vice President, Clinical and Regulatory Affairs. "The logic of this approach was suggested in a Commentary in the January 1997 issue of the journal Lancet." Further, PDL's former Ostavir development partner has conducted studies in a compassionate use setting in which two patients with chronic active hepatitis B treated with Ostavir and lamivudine have had no drug-related adverse events in long-term treatment.



"Nucleoside analogs such as lamivudine are understood to significantly inhibit viral replication inside cells although they do not prevent all viral particles from escaping and infecting regenerating liver cells," said Lars Ostberg, M.D., Director, Clinical Science. "In contrast, Ostavir is believed to block the hepatitis B virus from entering cells. The combination of lamivudine and Ostavir thus may reduce intracellular viral replication and protect uninfected cells, although such results remain to be determined in clinical testing. Results of multiple-drug treatment (triple therapy) of human immunodeficiency virus (HIV) disease suggest that drug regimens which include a nucleoside analog and other antiviral agents may be more effective than single-drug therapy of that disease," Dr. Ostberg said.



Protein Design Labs, Inc. is a leader in the development of humanized and human antibodies to prevent or treat various disease conditions. Zenapax™, a humanized antibody created by PDL, has been approved in the U.S. and Switzerland for the prophylaxis of acute organ rejection in patients receiving renal transplants. Zenapax is being marketed by Hoffmann-La Roche Inc. and its affiliates (Roche) and PDL receives royalties on Roche's product sales. PDL's antibodies have a longer half-life and are less immunogenic than mouse antibodies, and PDL therefore believes they will be more useful as human therapeutics. PDL holds fundamental U.S. and European patents for its antibody humanization technology. In addition, PDL holds exclusive licenses to patents that cover Ostavir and the trioma technology used to make Ostavir and certain other human antibodies.