FDA granted approval to vemurafenib for Erdheim-Chester Disease

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 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202429s016lbl.pdf.

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: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

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).

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