Mifamurtide

Mifamurtide is an immunomodulator with antitumor activity via activation of macrophages and monocytes. Also called L-MTP-PE, mifamurtide may be a liposomal form of of the active ingredient MTP-PE, which is a synthetic, less pyrogenic, and longer-acting derivative of muramyl dipeptide (MDP). MDP is a motif present in all gram-positive and gram-negative bacterial walls that is recognized by different signalling molecules and activators such as nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and toll-like receptors present in macrophages and monocytes. The overall result of MDP recognition leads to the production of proinflammatory cytokines and promotion of bactericidal and tumoricidal effects ^A31745. As a liposomal formulation, mifamurtide demonstrates an enhanced tumoricidal effect and improved safety profile ^A31745.

Mifamurtide is marketed in Europe as Mepact for intravenous infusion. It is administered as an adjuvant therapy to postoperative combination chemotherapy in pediatric, adolescent or adult patients with high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection. In the US, it is currently under investigation that holds orphan drug status for the treatment of osteosarcoma ^A31746.

Osteosarcoma is the most common primary malignant bone tumor that usually arises in the metaphyses of long bone in children and adolescents ^A31744. The standard therapy for osteosarcoma is comprised of macroscopic surgical resection and multi-agent chemotherapy consisting of doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue, and ifosfamide ^A31744. While about 90% of patients with newly diagnosed osteosarcoma may achieve complete remission from first-line therapies, the prognosis is still poor for patients with non-metastatic osteosarcoma with lower 5-year event-free survival. In a large, randomized, open-label, multicenter, phase III trial, the treatment of mifamurtide in conjunction with three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with significant improvement in survival rates and good tolerance ^A31746. The adverse events (AEs) associated with mifamurtide were generally mild to moderate in severity ^A31748.