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Genentech's Zelboraf Gets FDA Approval in BRAF Mutation-Positive Erdheim-Chester Disease

NEW YORK (GenomeWeb) – The US Food and Drug Administration today approved Genentech's BRAF inhibitor Zelboraf (vemurafenib) for Erdheim-Chester disease based on data from a basket trial involving 22 patients, the first time a drug has been approved based solely on such a trial.

Erdheim-Chester is a rare illness that results in the over-accumulation of white blood cells, called histocytes, in tissues and organs, and can result in organ failure. FDA approved Zelboraf specifically for patients with BRAF V600 mutations. There are fewer than 500 Erdheim-Chester cases in the US each year, 50 percent of whom harbor BRAF V600 mutations.

The agency approved the drug based on data from a Phase II basket trial that reported a best overall response rate of 54.5 percent among 22 people with the disease. Patients in the study experienced common Grade 3 or higher adverse events, such as new skin cancers, high blood pressure, rash, and joint pain.

Zelboraf is already approved for metastatic melanoma patients with BRAF V600E mutations. The drug was approved in 2011 alongside Roche's qPCR-based Cobas 4800 BRAF V600 Mutation Test for identifying melanoma patients with such mutations who would most likely respond best to treatment. 

The FDA granted Zelboraf breakthrough therapy designation and priority review for the Erdheim-Chester indication. "This FDA decision means people living with Erdheim-Chester disease will now, for the first time, have an FDA-approved treatment option," Sandra Horning, Genentech chief medical officer, said in a statement.

This is the first time a drug has been approved solely based on the results from a basket trial, which is an adaptive approach that allows the investigation of treatments by genomic signature instead of tumor site. The VE-BASKET study, published in the New England Journal of Medicine two years ago, enrolled patients with BRAF V600 mutation-positive cancers and other disease to evaluate if they'd respond to Zelboraf.  

A number of drugmakers are increasingly utilizing the novel, adaptable study design in evaluating responses to treatments in rare disease subtypes, and data from such trials is starting to show up in FDAsubmissions. For example, in garnering approval for Keytruda in a tumor-agnostic, biomarker-informed drug indication earlier this year, Merck submitted data from a basket trial.