Mifamurtide

Summary

Mifamurtide (MTP-PE) is a lipophilic muramyl dipeptide analog encapsulated in liposomes (L-MTP-PE), approved in the European Union for the treatment of high-grade, resectable, non-metastatic osteosarcoma in children, adolescents, and young adults following complete surgical resection, used in combination with post-operative multi-agent chemotherapy. It is not approved by the FDA in the United States.

Mechanism of Action

Mifamurtide is a synthetic analog of muramyl dipeptide (MDP), a component of bacterial cell walls. It activates monocytes and macrophages through NOD2 receptor signaling, stimulating the production of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-8) and enhancing tumoricidal activity, thereby augmenting the innate immune response against osteosarcoma cells.

Routes of Administration

Goals & Uses

• Immunostimulation / macrophage activationImmunologyModerate
• Prevention of metastatic relapseOncologyModerate
• Osteosarcoma adjuvant treatmentOncologyHigh
• Investigational use in other sarcomasOncologyLow

Contraindications

• Hypersensitivity to mifamurtide or liposomal componentsAllergyHigh
• Concurrent high-dose NSAIDs or corticosteroidsDrug InteractionHigh
• Concurrent use of cyclosporine or other calcineurin inhibitorsDrug InteractionHigh
• Active autoimmune or inflammatory disease requiring immunosuppressionDisease StateModerate

Adverse Effects

• Anemia / thrombocytopeniaHematologicUncommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Fever and chillsConstitutionalCommon
• Nausea and vomitingGastrointestinalCommon
• Tachycardia and hypertensionCardiovascularUncommon
• FatigueGeneralCommonLow energy or tiredness

Drug Interactions

• Corticosteroids (high-dose)High
• CyclosporineHigh
• NSAIDsModerateMay increase renal risk in susceptible patients
• Doxorubicin / Cisplatin / MethotrexateLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Adults over 30 yearsAgeRelative
• Patients with severe hepatic or renal impairmentOrgan ImpairmentRelative
• Patients with active infectionsInfectious DiseaseRelative
• Children under 2 yearsPediatricRelative

Regulatory Status

• European UnionApprovedApproved: High-grade resectable non-metastatic osteosarcoma in patients aged 2–30 years following complete surgical resection, in combination with post-operative chemotherapyApproved by EMA in March 2009 under exceptional circumstances; orphan medicine designation.
• United StatesUnapprovedFDA did not approve; orphan drug designation granted but efficacy from INT-0133 deemed insufficient for approval. Not commercially available in the US.
• United KingdomApprovedApproved: High-grade resectable non-metastatic osteosarcoma in patients aged 2–30 years following complete surgical resectionRetained EU approval post-Brexit via MHRA; available under the Mepact brand.

Approved by the EMA in 2009 under the brand name Mepact for osteosarcoma in patients 2–30 years of age. The FDA did not approve it, citing insufficient evidence of efficacy from the pivotal INT-0133 trial. Orphan drug designation granted in both EU and US.

Evidence & Sources

No sources recorded yet.