Mifamurtide

Lifetime effectiveness of mifamurtide addition to chemotherapy in nonmetastatic and metastatic osteosarcoma: a Markov process model analysis.[Pubmed:25835978]

Tumour Biol. 2015 Sep;36(9):6773-9.

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 % (10.13 and 9.17 QALY with and without Mifamurtide, respectively) and 45.2 % (7.23 and 4.98 QALY with and without Mifamurtide, respectively) relative to the lifetime effectiveness of chemotherapy in nonmetastatic and metastatic osteosarcoma, respectively. Life-years gained (LYG) increased by 10.1 % (13.10 LYG with Mifamurtide and 11.90 LYG without Mifamurtide) in nonmetastatic patients and 42.2 % (9.43 LYG with Mifamurtide and 6.63 LYG without Mifamurtide) in metastatic osteosarcoma patients. The Markov model analysis showed that chemotherapy with Mifamurtide improved the lifetime effectiveness compared to chemotherapy alone in both nonmetastatic and metastatic osteosarcoma. Relative effectiveness of the therapy was higher in metastatic than nonmetastatic osteosarcoma over lifetime. However, absolute lifetime effectiveness was higher in nonmetastatic than metastatic osteosarcoma.

Orphan drugs revisited: cost-effectiveness analysis of the addition of mifamurtide to the conventional treatment of osteosarcoma.[Pubmed:25354299]

Expert Rev Pharmacoecon Outcomes Res. 2015 Apr;15(2):331-40.

INTRODUCTION: Mepact((R)) (Mifamurtide) is the first drug approved for the treatment of high-grade resectable non-metastatic osteosarcoma in patients aged 2-30 in the last 20 years. It follows a randomized clinical trial showing a statistically-significant and clinically-relevant decrease in the risk of death without compromising safety. AIM: This study assessed the cost-effectiveness and budget impact of Mifamurtide. METHODS: The economic evaluation was done on a hypothetical cohort of young patients under the age of 30 with high-grade, non-metastatic, resectable osteosarcoma. Standard chemotherapy without Mifamurtide was used as comparator. A Markov model was adapted using Spanish costs and the results of the INT-0133 Phase III study. The analysis has been carried out from the perspective of the Spanish National Health Service, with a time horizon of up to 60 years in the base analysis. RESULTS: The observed greater efficacy of Mifamurtide in the trial translates into a gain of 3.03 (undiscounted) and 1.33 (discounted) quality-adjusted life years at an additional cost of euro102,000. The estimated budgetary impact of using Mifamurtide in 10-100% of the potential population would cost euro671,000 and euro6.7 million respectively. CONCLUSION: The cost per quality-adjusted life years gained with Mifamurtide in Spain is in the low band (

The Role of Mifamurtide in Chemotherapy-induced Osteoporosis of Children with Osteosarcoma.[Pubmed:27993113]

Curr Cancer Drug Targets. 2017;17(7):650-656.

BACKGROUND: Osteosarcoma is the most frequent malignant bone tumor in childhood and young adulthood. Long-term survivors of osteosarcoma patients show high prevalence of osteoporosis and fractures. The immunomodulatory Mifamurtide, which modulates macrophages activity, improves disease outcome. OBJECTIVE: To evaluate the role of Mifamurtide on macrophage component of bone, the osteoclasts, during chemotherapy in children with osteosarcoma. METHOD: Osteoclasts, obtained from peripheral blood cells of healthy donors were harvested in the presence or not of Mifamurtide. Moreover, osteoclast cultures were obtained from osteosarcoma patients, at onset and during chemotherapy, alone or with Mifamurtide. Pro-osteoporotic tartrateresistant acid phosphatase (TRAP), phosphokinase-beta-2 (PKCbeta2), vanilloid receptor type 1 (TRPV1), and anti-osteoporotic cannabinoid receptor type 2 (CB2) biomarkers were analyzed by bio-molecular (qPCR), biochemical (Western Blotting), and morphological (TRAP assay) approaches. RESULTS: Osteoclasts from osteosarcoma patients show significant increase of TRAP and decrease of CB2 with respect to osteoclasts from healthy donors. This osteoclast hyperactivity is more evident in osteoclasts from osteosarcoma patients during chemotherapy. Mifamurtide reduces pro-osteoporotic TRAP, PKCbeta2, TRPV1 levels and increases CB2 in osteoclasts from healthy donors. Moreover, chemotherapy-induced effects on bone resorption markers are fully reverted in osteoclasts derived from osteosarcoma patients in chemotherapy plus Mifamurtide. CONCLUSION: Our data suggest a new therapeutic role for Mifamurtide as possible anti-resorption agent in chemotherapy-induced osteoporosis in children with osteosarcoma.