November 6, 2017
On November 6, 2017, the Food and Drug Administration granted regular approval to vemurafenib (ZELBORAF®, Hoffmann-La Roche Inc.) for the treatment of patients with Erdheim-Chester Disease (ECD) with BRAF V600 mutation.
Approval was based on an open-label, multicenter, single-arm, multiple cohort clinical trial in patients aged 16 years of age and older. The trial included 22 patients with BRAF V600 mutation- positive ECD. The best overall response rate, as assessed by the investigator using RECIST 1.1, was 54.5% (n=12) (95% CI: 32.2, 75.6). Eleven partial responses (50%) and 1 complete response (4.5%) were observed. The median duration of follow- up was 26.6 months (range: 3.0 to 44.3 months). The median time to response was 11 months (95% CI: 3.7, 14.6). The median response duration was not estimable.
In the trial, the most commonly reported adverse reactions (>50%) in patients with BRAF V600 ECD were arthralgia, rash maculo papular, alopecia, fatigue, electrocardiogram QT prolonged, and skin papilloma. The most common (≥ 10%) Grade ³ 3 adverse reactions were squamous cell carcinoma of the skin, hypertension, rash maculo-papular, and arthralgia. The incidence of adverse reactions resulting in permanent discontinuation was 32%.
The recommended dose of vemurafenib is 960 mg orally twice daily taken approximately 12 hours apart with or without a meal.
Full prescribing information is available at
FDA granted this application priority review. Breakthrough Therapy and Orphan Drug designations for this indication were also granted. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).