Vemurafenib Granted FDA Approval to Treat Rare Blood Cancer

The FDA has approved the BRAF inhibitor vemurafenib (Zelboraf) as a treatment for patients with BRAFV600-mutated Erdheim-Chester disease (ECD), representing the first approved therapy for this rare blood disorder.

The approval was based on findings from the phase II VE-BASKET study, which included 22 patients with the rare, non-Langerhans histiocytic neoplasm. In the trial, patients with ECD treated with vemurafenib had an objective response rate (ORR) of 54.5%, which consisted of a partial response for 11 patients and 1 complete response. After 26.6 months of follow-up, the median progression-free survival, duration of response, and overall survival were not yet reached.

“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,” Richard Pazdur, MD, 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, said in a statement. “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 most frequently reported all-grade adverse events (AEs) were creatinine elevation (86%), arthralgia (82%), maculopapular rash (59%), alopecia (55%), fatigue (55%), QT interval prolongation on electrocardiogram (55%), and skin papilloma (55%). The most common grade ≥3 AEs were cutaneous squamous cell carcinoma (cuSCC; 36%), hypertension (23%), maculopapular rash (18%), and arthralgia (14%). The median time to appearance of first cuSCC was 12.1 weeks following treatment with vemurafenib.

The approval for vemurafenib arrived approximately 1 month ahead of a deadline set by the Prescription Drug User Fee Act. Initial results from the basket study were published in 2015, and prior to approval the agent was granted a breakthrough therapy designation and orphan drug designation.