Mifamurtide - CAS 83461-56-7
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Not Intended for Therapeutic Use. For research use only.
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Mifamurtide is a liposomal formulation containing a muramyl dipeptide (MDP) analogue with potential immunomodulatory and antineoplastic activities. It is a derivative of the mycobacterial cell wall component MDP and activates both monocytes and macrophages. It is an immunomodulator with antitumor effects that appear to be mediated via activation of monocytes and macrophages. It has orphan drug status for the treatment of osteosarcoma in the US and EU.
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Mepact; CGP-19835; MTP-PE; MTP-cephalin; L-MTP-PE; MLV19835
1.Macrophages inhibit human osteosarcoma cell growth after activation with the bacterial cell wall derivative liposomal muramyl tripeptide in combination with interferon-γ.
Pahl JH, Kwappenberg KM, Varypataki EM, Santos SJ, Kuijjer ML, Mohamed S, Wijnen JT, van Tol MJ, Cleton-Jansen AM, Egeler RM, Jiskoot W, Lankester AC, Schilham MW1. J Exp Clin Cancer Res. 2014 Mar 10;33:27. doi: 10.1186/1756-9966-33-27.
BACKGROUND: In osteosarcoma, the presence of tumor-infiltrating macrophages positively correlates with patient survival in contrast to the negative effect of tumor-associated macrophages in patients with other tumors. Liposome-encapsulated muramyl tripeptide (L-MTP-PE) has been introduced in the treatment of osteosarcoma patients, which may enhance the potential anti-tumor activity of macrophages. Direct anti-tumor activity of human macrophages against human osteosarcoma cells has not been described so far. Hence, we assessed osteosarcoma cell growth after co-culture with human macrophages.
2.The addition of mifamurtide to chemotherapy improves lifetime effectiveness in children with osteosarcoma: a Markov model analysis.
Song HJ1, Lee EK, Lee JA, Kim HL, Jang KW. Tumour Biol. 2014 Sep;35(9):8771-9. doi: 10.1007/s13277-014-2139-y. Epub 2014 May 30.
In the absence of long-term clinical trials that compare mifamurtide plus chemotherapy versus chemotherapy only for treatment of osteosarcoma, decision analysis is a useful tool that helps to determine the optimal treatment strategy. We analyzed the differences between mifamurtide plus chemotherapy versus chemotherapy only by using modeling to determine the treatment approach that results in longer life expectancy among children with osteosarcoma. We used the Markov model to compare the expected lifetime quality-adjusted life years (QALYs) between mifamurtide plus chemotherapy versus chemotherapy only. Our target cohort consisted of children with osteosarcoma. The starting age of the cohort was 12 years and cycle length was 3 months. The transition probabilities for each disease state and death were calculated using overall survival or progression free survival data from randomized controlled trials. Utility weights from scenario-based survey for 303 Korean general populations were applied to the model.
3.Lifetime effectiveness of mifamurtide addition to chemotherapy in nonmetastatic and metastatic osteosarcoma: a Markov process model analysis.
Song HJ1, Lee JA2, Han E3, Lee EK4. Tumour Biol. 2015 Sep;36(9):6773-9. doi: 10.1007/s13277-015-3405-3. Epub 2015 Apr 3.
The mortality and progression rates in osteosarcoma differ depending on the presence of metastasis. A decision model would be useful for estimating long-term effectiveness of treatment with limited clinical trial data. The aim of this study was to explore the lifetime effectiveness of the addition of mifamurtide to chemotherapy for patients with metastatic and nonmetastatic osteosarcoma. The target population was osteosarcoma patients with or without metastasis. A Markov process model was used, whose time horizon was lifetime with a starting age of 13 years. There were five health states: disease-free (DF), recurrence, post-recurrence disease-free, post-recurrence disease-progression, and death. Transition probabilities of the starting state, DF, were calculated from the INT-0133 clinical trials for chemotherapy with and without mifamurtide. Quality-adjusted life-years (QALY) increased upon addition of mifamurtide to chemotherapy by 10.5 % (10.
4.NICE's selective application of differential discounting: ambiguous, inconsistent, and unjustified.
O'Mahony JF1, Paulden M2. Value Health. 2014 Jul;17(5):493-6. doi: 10.1016/j.jval.2013.02.014. Epub 2013 May 15.
The National Institute for Health and Clinical Excellence (NICE) recently recommended differential discounting of costs and health effects in the economic appraisal of health care interventions in certain circumstances. The recommendation was published in an amendment to NICE's Guide to the Methods of Technology Appraisal. The amendment states that differential discounting should be applied where "treatment effects are both substantial in restoring health and sustained over a very long period (normally at least 30 years)." Renewed interest in differential discounting from NICE is welcome; however, the recommendation's selective application of differential discounting raises a number of concerns. The stated criteria for applying differential discounting are ambiguous. The rationale for the selective application of differential discounting has not been articulated by NICE and is questionable. The selective application of differential discounting leads to several inconsistencies, the most concerning of which is the lower valuation of health gains for those with less than 30 years remaining life expectancy, which can be interpreted as age discrimination.
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CAS 83461-56-7 Mifamurtide

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