FDA Approves Vemurafenib for Treating Erdheim-Chester Disease

Vemurafenib is the first FDA-approved drug for the treatment of Erdheim–Chester disease

The US Food and Drug Administration (FDA) has expanded the approval of vemurafenib (Zelboraf) to include the treatment of a rare, slow-growing blood cancer, Erdheim–Chester disease, for adult BRAF V600­­–positive patients. This marks the first approval from the agency for treating the disease.

Erdheim–Chester disease originates in the bone marrow and is characterized by the abnormal multiplication of histiocytes, which can invade normal tissue and organs, including the brain, heart, lungs, and others. Each year the disease is estimated to affect 600 to 700 patients worldwide. More than half of patients with Erdheim–Chester disease carry the BRAF V600­­ mutation.

“Today’s approval of Zelboraf for patients with Erdheim-Chester disease demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a press release. “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.”

The approval was based on results of the phase II basket study VE-BASKET, an open-label, non-randomized trial that studied vemurafenib in a number of BRAF V600 mutation–positive cancers. Twenty-two people with Erdheim–Chester disease were included in the trial-11 patients achieved a partial response and 1 patient achieved a complete response, for an overall response rate of 54.5%. At 26.6 months follow-up, the median duration of response was not yet reached.

The most common grade 3 or higher adverse events among vemurafenib-treated patients (≥ 10%) were arthralgia, high blood pressure, rash, and squamous cell carcinoma of the skin. The most common adverse events (≥ 50%) were alopecia, arthralgia, change in heart rhythm, fatigue, maculopapular rash, and papilloma.

Other severe side effects of vemurafenib include anaphylaxis, DRESS syndrome, Dupuytren contracture, hepatotoxicity, photosensitivity, plantar fascial fibromatosis, QT prolongation, radiation sensitization and recall, renal failure, Stevens–Johnson Syndrome, toxic epidermal necrolysis, and uveitis.