Mifamurtide (Ciba-Geigy)

L-MTP-PE (also known as mifamurtide) is a synthetic derivative of muramyl dipeptide (MDP) that is encapsulated in liposomes for therapeutic use. It functions as an immunomodulator that activates macrophages and monocytes to target cancer cells, particularly in osteosarcoma treatment. ## Composition and Structure Mifamurtide is chemically described as muramyl tripeptide phosphatidylethanolamine (MTP-PE). It's a fully synthetic derivative of muramyl dipeptide, which is a component found in bacterial cell walls[1][2]. The liposomal formulation (L-MTP-PE) enhances its tumoricidal effect and improves its safety profile by allowing better distribution to the liver, spleen, and lungs after intravenous administration[5]. ## Mechanism of Action L-MTP-PE works by selectively being phagocytosed by monocytes and macrophages. After the liposomal vesicles are degraded by these phagocytic cells, MTP-PE is released into the cytosol where it interacts with Nod2 and activates the macrophages and monocytes[5]. This activation leads to: 1. Production of proinflammatory cytokines 2. Promotion of bactericidal and tumoricidal effects The drug targets Toll-like receptor 4 and Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) as its primary mechanisms[5]. ## Clinical Use and Approval Status L-MTP-PE is primarily indicated for the treatment of high-grade, non-metastatic, resectable osteosarcoma following complete surgical removal in children, adolescents, and young adults aged 2-30 years[2]. It's used in combination with postoperative, multiagent chemotherapy to eliminate remaining cancer cells and improve overall survival rates. The drug was approved in Europe in March 2009 under the trade name Mepact, marketed by Takeda[2]. It received approval in 27 European Union member states plus Iceland, Liechtenstein, and Norway. However, the FDA denied approval for L-MTP-PE in the United States in 2007[3]. ## Clinical Evidence In a phase III clinical trial involving approximately 800 newly diagnosed osteosarcoma patients, L-MTP-PE combined with chemotherapeutic agents showed a 30% reduction in mortality compared to chemotherapy plus placebo. Six years after treatment, 78% of patients were still alive, representing an absolute risk reduction of 8%[2]. ## Development History The drug was originally invented by Ciba-Geigy (now Novartis) in the early 1980s and was later sold to Jenner Biotherapies in the 1990s. In 2003, IDM Pharma acquired the rights and continued its development. Takeda subsequently acquired IDM Pharma along with mifamurtide in June 2009[2]. L-MTP-PE had been granted orphan drug status by both the FDA in 2001 and the European Medicines Agency in 2004[2].

Brand names

Mepact

Other names

L-MTP-PEmuramyl tripeptide phosphatidylethanolamine