Oregovomab: anti-CA-125 monoclonal antibody B43.13--AltaRex, B43.13, MAb B43.13, monoclonal antibody B43.13.

ViRexx Medical Corp is developing the murine monoclonal antibody oregovomab [OvaRex, MAb B43.13] for the treatment of ovarian cancer. Oregovomab targets the circulating tumour-associated antigen CA 125, which is shed from the surface of human ovarian cancer cells; the antibodies induce broad cellular and humoral immune responses against CA 125 via complex formation. Unlike free CA 125, CA 125-oregovomab complexes can prime dendritic cells, leading to downstream activation of T cells. The antibody is undergoing advanced clinical development. AltaRex, the originator of oregovomab, was acquired by, and merged into, ViRexx Medical Corp in December 2004. AltaRex (now ViRexx Medical Corp) has established several strategic corporate alliances for the development and/or commercialisation of oregovomab. Unither Pharmaceuticals, a subsidiary of United Therapeutics Corporation, entered into a licensing agreement with ViRexx in April 2002. The agreement covers most territories worldwide, except Europe and the Middle East, which are covered by other agreements (see below); ViRexx did retain the rights to most member nations of the EU and certain other countries. In August 2003, the agreement was extended, granting United Therapeutics Corporation development rights for Germany. AltaRex and Dompe entered into a distribution agreement for oregovomab in July 2004. Territories included in the agreement are Italy, Spain, Portugal, Hungary, Poland, Czech Republic, Switzerland, Austria and certain other Eastern European countries. Under the terms of the agreement, ViRexx retains responsibility for product development and registration of the antibody, upon commercialisation in the agreed territory. The two companies will work closely to achieve product registration throughout Europe. In June 2001, Dompe entered into a sublicensing agreement with FAES for the commercialisation of oregovomab in Spain and Portugal. ViRexx is also seeking collaboration partners for Northern European markets. Medison Pharma and AltaRex entered into an agreement in April 2002. Under the terms of the agreement, the two companies will establish a joint venture to market oregovomab in Israel and the Middle East. ViRexx also has an agreement with Genesis Pharma covering the commercialisation of the antibody in Greece, Turkey, Cyprus and the Balkans. Unither Pharmaceuticals has completed trial enrollment for its two pivotal phase III trials investigating oregovomab for the treatment of advanced ovarian cancer. In June 2006, Unither reached its enrollment goal of 177 patients for the IMPACT II study, the second of two identical double-blind, placebo-controlled trials. The IMPACT I study achieved its enrollment target in December 2005. Both IMPACT studies are designed to assess the effect of oregovomab on time to disease relapse in patients with advanced ovarian cancer (stage III/IV) who have achieved an optimal response with front-line chemotherapy, and are being conducted at over 60 sites across the US. Data from the studies are intended to support registration of the antibody in the US. ViRexx also plans to utilise results from the IMPACT studies to support regulatory filings in Europe and in other countries. In addition, a phase II trial is being conducted to evaluate two dosing regimens of adjunctive oregovomab plus platinum-based first-line chemotherapy in patients with advanced ovarian cancer. The enrollment target of 40 patients has been achieved; primary study analysis is anticipated to be completed by the end of 2006. Several phase II trials with oregovomab as monotherapy or in combination with other chemotherapeutics have been completed across the US and Canada. Clinical trials have also been conducted in the EU, but ViRexx has suspended such EU studies on the basis of commercial considerations. Oregovomab has orphan drug status for the treatment of ovarian cancer; designation was granted by the US and the EU in 1996 and 2002, respectively. In addition, the US FDA granted fast-track status to the antibody in 1998. AltaRex (now ViRexx Medical Corp) has been awarded the US patent covering the company's technology for administering a low dose of foreign antibody to patients expressing the CA 125 antigen. A second US patent has also been issued for oregovomab covering the technique of photoactivation using ultraviolet light to modify antibodies and enhance specific beneficial immune responses. Furthermore, AltaRex was granted a 'multi-epitopic' patent application covering oregovomab by the European Patent Office (EPO) in October 2003. The patent covers the company's technology of IV administration of a low-dose foreign antibody, such as oregovomab, to patients expressing the target tumour-associated antigen CA 125. The EPO's grant of the patent for the European Union enables intellectual property protection of oregovomab in the great majority of worldwide markets.