FDA approves new drug Zelboraf for Erdheim-Chester disease

By Dr. Ananya Mandal, MDNov 6 2017

The United States Food and Drugs Administration (FDA) has approved Zelboraf (vemurafenib), a drug for the treatment of adults with a are type of blood cancer called Erdheim-Chester Disease or ECD.

Zelboraf (vemurafenib) is already approved for the treatment of persons with a certain type of genetic mutation called the BRAF V600E leading to cancers such as skin cancers or melanomas. Now the approval has been extended to ECD. This is the first drug approved for this rare type of blood cancer.

Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research in his statement said, “Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers…This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”

According to the FDA statement, ECD is a slowly progressing type of blood cancer. It starts in the bone marrow. There is an increased production of a certain type of cells called histiocytes. These are a type of white blood cells and excess numbers of these get accumulated in several organs of the body such as heart, lungs, brain etc. There are 600 to 700 individuals worldwide with this rare form of cancer. They do not live long and around one in two of these patients have the BRAF V600 genetic mutation. This new drug Zelboraf is a kinase inhibitor. This can stop the cell growth in certain types of cells by blocking certain key enzymes.

For approval, the manufacturers who have been now granted approval - Hoffman-LaRoche, Inc -submitted results from a clinical trial that showed its effectiveness and safety in these patients. They tested the drug on 22 patients with ECD who were positive for the BRAF-V600-mutation. They tested for partial or complete reduction in the tumor size and called it an overall response rate. Eleven patients of the 22 showed partial response to the drug in tumor reduction while 1 patients showed a complete response with complete tumor reduction. This proved the efficacy of the new drug.

The trial also looked at the safety of this medication and found that Zelboraf leads to joint pain, raised rash, tiredness, skin growths, loss of hair and change in the electrical activity of the heart. Sometimes Zelboraf may lead to development of secondary cancers such as those of skin or squamous cell carcinomas etc. It may also cause BRAF wild-type melanoma or skin cancer worsening and lead to allergic reactions such as anaphylaxis or Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) that could become fatal or life-threatening. The drug may rarely lead to heart rhythm abnormalities or arrhythmias and also severe liver damage. It may damage the eyes or may lead to kidney damage. Pregnant women should not be given this medication as it may severely harm the growing fetus.

Zelboraf received a priority review and got an orphan drug status. This means that the drug was approved for few numbers of patients who have a rare disease or condition. These incentives encourage new drug development in rare conditions.