Genentech, a member of the Roche Group, announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) and granted Priority Review for 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. Zelboraf was also granted Breakthrough Therapy Designation (BTD) by the FDA for this indication. The FDA is expected to make a decision on approval by December 7, 2017.
The sNDA includes data from the open-label, 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 allows researchers to evaluate multiple diseases simultaneously. This is particularly important for diseases that are extremely rare, making it difficult to fully enroll a disease- or tumor-specific trial.
“This first potential treatment submitted to the FDA for this rare disease was identified by an innovative trial studying Zelboraf across different diseases with the same genetic mutation,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are committed to bringing new treatment options to people with rare diseases and hope to see Zelboraf approved for Erdheim-Chester disease as soon as possible.”
A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. This is the sixteenth Breakthrough Therapy Designation granted to Genentech medicines since 2013 – the most of any company in the industry.
About the VE-BASKET Study
VE-BASKET is a 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 percent by RECIST v1.1. The median duration of response, progression-free survival and overall survival were not reached at a median follow-up time of 26.6 months. The most common adverse events were joint pain, rash, hair loss, change in heart rhythm, fatigue, skin tags, diarrhea and thickening of the skin. The most common Grade 3 or higher adverse events were new skin cancers, high blood pressure, rash and joint pain. Initial study results were published in the New England Journal of Medicine in August 2015.
About Erdheim-Chester Disease
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. More than 50 percent of people with ECD have BRAF V600 mutation-positive disease. No large studies have been performed and there are currently no approved treatments for ECD.
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.