Vemurafenib Receives FDA Approval for Treatment of Rare Erdheim-Chester Disease

The U.S. Food and Drug Administration expanded the approval of the kinase inhibitor vemurafenib to include adults with Erdheim-Chester disease (ECD) and the BRAF V600 mutation, making this the first FDA-approved treatment for ECD – a rare, serious blood disease characterized by the abnormal multiplication of certain white blood cells called histiocytes .

The indication was based on results from the open-label, multicenter, single-arm, multicohort, phase II VE-BASKET study, which enrolled 22 patients with BRAF V600–positive ECD to receive vemurafenib. After a median follow-up of 26.6 months (range = 3.0-44.3 months), the best overall response rate (ORR) was 54.5 percent (n=12; 95% CI 32.2-75.6). Fifty percent of patients (n=11) experienced a PR, and 4.5 percent (n=1) experienced a CR. The median time to response was 11 months (95% CI 3.7-14.6; range not provided), and the median duration of response was not estimable.

AEs associated with vemurafenib include arthralgia, maculo-papular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe AEs include SPMs (including skin cancer, squamous cell carcinoma, and others), growth of tumors in those with BRAF wild-type melanoma, anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, QT prolongation, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and recall, Dupuytren’s contracture, and plantar fascial fibromatosis. Thirty-two percent of patients discontinued treatment because of AEs.

The recommended dose of vemurafenib is 960 mg taken orally twice-daily.

Vemurafenib previously received priority review, breakthrough-therapy, and orphan-drug designation for the treatment of ECD. The drug was approved for BRAF V600–positive metastatic melanoma.

Sources: U.S. Food and Drug Administration news releases, November 6, 2017.