FDA Approves Zelboraf for Erdheim-Chester Disease

Treatment for rare blood disease targets patients with BRAF V600 mutation

The FDA has approved vemurafenib (Zelboraf, Genentech) for Erdheim-Chester disease (ECD) with BRAF V600 mutation. ECD is a rare, serious blood disease characterized by the abnormal multiplication of white blood cells called histiocytes, which can invade normal tissues and organs in the body.

The approval is based on data from the phase 2 VE-BASKET study. Basket studies use a clinical trial design that helps collect data faster and may accelerate the development of medicines for diseases with high unmet need. Instead of enrolling people based primarily on their disease or its location, basket studies match a disease’s underlying genetic profile to the mechanism of action of the medicine.

“The Erdheim-Chester disease community is very encouraged by this first FDA-approved treatment for ECD, bringing new hope to patients and their families," said Kathleen Brewer, president of ECD Global Alliance. "This new treatment option shows that meaningful breakthroughs can occur rapidly when patients, families, research physicians, industry, and the FDA work together to help patients.”

The open-label, non-randomized VE-BASKET study is investigating the use of vemurafenib for people with BRAF V600 mutation-positive cancers and other diseases, including ECD. Final results for the 22 people with ECD showed a best overall response rate of 54.5% by RECIST v1.1. The median duration of response was not estimable at a median follow-up time of 26.6 months.

The most common grade 3 or higher adverse events (10% or more) were new skin cancers, high blood pressure, rash, and joint pain. The most common adverse events (more than 50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. Initial study results were published in the New England Journal of Medicine in August 2015.

Vemurafenib monotherapy was approved for the treatment of people with unresectable or metastatic melanoma with BRAF V600E mutation in 2011. The FDA previously granted priority review and breakthrough therapy designations to vemurafenib for ECD with BRAF V600 mutation.

ECD is an extremely rare non-Langerhans cell histiocytosis. The exact prevalence and incidence of ECD are difficult to ascertain because the disease is so rare. Based on available published data, it’s estimated there are fewer than 500 cases of ECD in the United States. More than 50% of people with ECD have BRAF V600 mutation-positive disease.

Vemurafenib is designed to inhibit some mutated forms of BRAF, which cause abnormal signaling inside cancer cells leading to tumor growth. BRAF is a protein in a cell signaling pathway that helps control cell growth and survival. Vemurafenib, the first approved product in its class, was codeveloped under a 2006 license and collaboration agreement between Roche (Genentech’s parent company) and Plexxikon, now a member of the Daiichi Sankyo Group.

Source: Genentech; November 6, 2017.