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When discovery collides with reality

CCH Newsletter - Spring 2013

The journey of an orphan drug

In 1982, Eugenie Kleinerman, M.D., division head of Pediatrics and head of the MD Anderson Children’s Cancer Hospital, began to study a medication named MEPACT (mifamurtide) and worked to get it to patients who had been newly diagnosed with resectable non-metastatic osteosarcoma.

She learned that the drug brought about the regression of melanoma lung metastases in mice. Because osteosarcoma most often metastasizes to the lungs, and many of these metastases are resistant to chemotherapy, these findings caught her attention.

In collaboration with the Division of Cancer Medicine, Kleinerman and James L. Murray, M.D., professor in the Department of Breast Medical Oncology, led the first clinical trial that took MEPACT from preclinical testing to Phase I testing in humans. This trial determined the optimal biologic dose of the drug and defined side effects. Patients 18 years and older participated because children can’t be included in the first Phase I trials.

Kleinerman also was principal investigator on the Phase II clinical trial of the drug for pediatric patients with relapsed osteosarcoma. These trials showed how MEPACT stimulated human immune cells to react against osteosarcoma cells.

The research eventually led to a Phase III national trial of about 700 newly diagnosed osteosarcoma patients, conducted by the Children’s Oncology Group.Patients were randomly assigned to receive chemotherapy alone or chemotherapy plus MEPACT.

Scientists found that MEPACT, when given in conjunction with combination chemotherapy, resulted in a 30% reduction in the mortality rate at eight years after diagnosis, compared to the patients who received chemotherapy alone. That number’s now increased to 15 years after diagnosis.

In 2007, with a new pharmaceutical company as their champion, the data from the Phase III trial was presented to the FDA, but the request for approval to use was denied. The FDA felt that another Phase III clinical trial, which would require approximately 900 patients with this rare disease, was needed.

Kleinerman believed that the odds were too great for this to occur, but the drug manufacturers pushed to take MEPACT to Europe. There, Kleinerman helped guide the drug through reviews by the European Medicines Agency. MEPACT was approved for pediatric patients with non-metastatic sarcoma in 2009, allowing it to be marketed in the 27 EU member states, as well as Iceland, Liechtenstein and Norway.

The National Institute for Clinical Excellence, the agency in the United Kingdom that determines which drugs will be covered by the government, approved MEPACT for newly diagnosed OS in 2011. Last September, MEPACT received a prestigious honor: the 2012 United Kingdom Prix Galien Orphan Drug award for international pharmaceutical research and development.

Kleinerman only wishes the news about MEPACT was so positive in the United States. But she believes that won’t happen without changes to the approval process for drugs used to treat diseases that primarily affect children.


© 2014 The University of Texas MD Anderson Cancer Center