Roche announced that the US Food and Drug Administration (FDA) has approved Zelboraf (vemurafenib) for Erdheim-Chester disease (ECD) with BRAF V600 mutation.

ECD is a rare, serious blood disease characterized by the abnormal multiplication of certain white blood cells called histiocytes, which can invade normal tissues and organs in the body.

The approval is based on data from the phase II VE-BASKET study. Basket studies use an innovative 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.

“This FDA decision means people living with Erdheim-Chester disease will now, for the first time, have an FDA-approved treatment option,” said Sandra Horning, MD, Roche’s chief medical officer and head of global product development. “We are committed to finding new ways to bring medicines to patients with high unmet need, and we are pleased that this innovative clinical trial helped identify Zelboraf for treatment of this rare disease.”

Final results of VE-BASKET for the 22 people with ECD showed a best overall response rate of 54.5 per cent. The most common Grade 3 or higher adverse events were new skin cancers, high blood pressure, rash and joint pain. The most common adverse events were joint pain, rash, hair loss, fatigue, change in heart rhythm and skin tags.

Zelboraf 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 Designation to Zelboraf for ECD with BRAF V600 mutation.

VE-BASKET is an open-label, Phase II, non-randomized, basket study investigating the use of Zelboraf 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 per cent by RECIST v1.1. The median duration of response was not estimated at a median follow-up time of 26.6 months. The most common Grade 3 or higher adverse events (=10 per cent) were new skin cancers, high blood pressure, rash and joint pain. The most common adverse events (=50 per cent) 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.

Erdheim-Chester disease (ECD) is an extremely rare non-Langerhans cell histiocytosis. The exact prevalence and incidence of ECD are difficult to ascertain given 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.5 More than 50 per cent of people with ECD have BRAF V600 mutation-positive disease.

Zelboraf 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. Zelboraf was the first approved product in its class. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon, now a member of the Daiichi Sankyo Group.