Mifamurtide
An immune activator for osteosarcoma, approved in Europe but not the US
Mifamurtide is a synthetic muramyl tripeptide linked to a phospholipid and carried in liposomes. It activates macrophages to attack osteosarcoma cells, especially in the lungs. The EU authorised it as Mepact in 2009 for young people with non-metastatic osteosarcoma after surgery, given with chemotherapy; it is not approved in the US.
What is it?
Muramyl dipeptide is the smallest part of the bacterial cell wall that the immune system recognises. Mifamurtide is a synthetic relative, muramyl tripeptide, joined to a phospholipid and packaged in liposomes that macrophages take up, particularly in the lungs, where osteosarcoma tends to spread. It is not toxic to tumour cells itself; it works by turning macrophages against them.
A pivotal Children's Oncology Group trial led to its approval in Europe and, by one review's count, in over 40 countries. Reviews summarise the result as a trend towards better event-free survival and a one-third reduction in the risk of death, or an 8% improvement in six-year overall survival in non-metastatic disease. Its short-term side effects are fever, headache, flu-like symptoms and rigors.
More recent data are mixed in emphasis. In a merged Italian and Spanish analysis of 398 patients, where mifamurtide was added for tumours with high P-glycoprotein, event-free survival was better with mifamurtide plus chemotherapy, and a 2025 gene-signature study is exploring which patients respond. In the US it is not approved.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Published Research
Studies of mifamurtide, from their PubMed abstracts.
The pivotal result
Adding muramyl tripeptide (mifamurtide) to chemotherapy for osteosarcoma produced a trend towards improved event-free survival and a one-third reduction in the risk of death; it was approved in Europe for newly diagnosed osteosarcoma with chemotherapy.
Practical review
Mifamurtide is not cytotoxic in vitro but activates immune cells against lung metastases; adding it to chemotherapy improved 6-year overall survival by 8% in non-metastatic and 5-year by 13% in metastatic osteosarcoma, with fever, headache, flu-like symptoms and rigors as short-term toxicities.
From dogs to approval
Preclinical studies, including dogs with spontaneous osteosarcoma, showed that L-MTP-PE could control microscopic metastases, and a pivotal trial led to its approval in over 40 countries.
Italian and Spanish cohort
Among 398 patients, where mifamurtide was added for P-glycoprotein-positive tumours, 5-year event-free survival was superior with mifamurtide plus chemotherapy than with chemotherapy alone; overall 5-year survival was 74.8%.
Who responds
In 62 patients, a 21-gene immune signature separated high-risk (5-year survival 47%) from low-risk (92%) patients and is being explored to predict response to chemotherapy plus mifamurtide.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
No US label; it is not approved in the US.
Legal Status
Mifamurtide is authorised in the EU but not in the US.
Frequently Asked Questions
?Is mifamurtide a peptide?
It is a small peptide, muramyl tripeptide, chemically joined to a phospholipid and packaged in liposomes, so it is classed here as a peptide conjugate.
?Is Mepact approved in the US?
No. It is authorised in the EU for non-metastatic osteosarcoma after surgery, in combination with chemotherapy, but has no FDA approval.
?How much does it help?
Reviews of the pivotal trial describe a trend towards better event-free survival and about a one-third reduction in the risk of death when added to chemotherapy.
?Why is mifamurtide packaged in liposomes?
The liposomes contain phosphatidylserine, a signal macrophages respond to, so both the active drug and its carrier target immune cells in the lungs, where osteosarcoma most often spreads.
?Who is mifamurtide for?
In the EU, children, adolescents and young adults aged 2 to 30 at diagnosis with high-grade, resectable, non-metastatic osteosarcoma, after complete surgical removal, together with postoperative multi-agent chemotherapy.
References
- [regulator] European Medicines Agency, medicines register (download of October 3, 2026): Mepact (mifamurtide), authorised, marketing authorisation date 06/03/2009, indication as stated. https://www.ema.europa.eu/en/medicines/human/EPAR/mepact
- [pubmed] Meyers PA. "Muramyl tripeptide (mifamurtide) for the treatment of osteosarcoma." Expert Rev Anticancer Ther, 2009;9(8):1035-49. PMID: 19671023.
- [pubmed] Anderson PM, et al. "Mifamurtide in osteosarcoma--a practical review." Drugs Today (Barc), 2010;46(5):327-37. PMID: 20517534.
- [pubmed] Meyers PA. "Muramyl Tripeptide-Phosphatidyl Ethanolamine Encapsulated in Liposomes (L-MTP-PE) in the Treatment of Osteosarcoma." Adv Exp Med Biol, 2020;1257:133-139. PMID: 32483736.
- [clinical-trial] Palmerini E, et al. "Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials." J Clin Oncol, 2025;43(28):3113-3122. PMID: 40825172.
- [pubmed] Palmerini E, et al. "Tumor Immune Microenvironment-Associated Prognostic and Mifamurtide-Response Gene Signatures for Localized Osteosarcoma: A Correlative Study of the ISG/OS-2 Trial." Clin Cancer Res, 2025;31(18):3932-3943. PMID: 40711479.
Sources & Citations
Studies were read from their PubMed records; regulatory sources are listed below, read October 3, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.