Bevacizumab Secures Approval in Japan as World's First Therapy for Neurofibromatosis Type 2

According to a new announcement, Japan's Ministry of Health, Labour and Welfare has approved Chugai Pharmaceutical’s bevacizumab, marketed as Avastin, for the treatment of patients with neurofibromatosis type 2 (NF2), marking it as the world's first regulatory clearance of any systemic agent for this rare hereditary disorder. This decision extends bevacizumab's oncology approvals to NF2 and provides clinicians with the first pharmacologic option for a condition historically managed through surgery, radiation, and observation.¹

"NF2 is a rare disease that causes symptoms such as hearing loss and dizziness, significantly impacting patients' daily lives, and there has been a strong need for effective treatment options," Osamu Okuda, MD, PhD, president and CEO at Chugai Pharmaceutical, said in a statement.¹ "Avastin represents a new therapeutic option, suggesting potential for the maintenance or improvement of hearing and a trend toward tumor reduction."

Drug Background

Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds vascular endothelial growth factor (VEGF), thereby blocking VEGF-mediated angiogenesis essential for tumor growth and metastasis.³ The drug has been commercially available in Japan since June 2007, where it carries approvals across 7 solid tumor types. Its biologic relevance in NF2 stems from evidence that VEGF overexpression contributes to the vascular pathobiology of vestibular schwannomas, a rationale supported by multiple prior retrospective and prospective observational series.

Trial Overview

The approval was supported by data from the BeatNF2 study (jRCT2080224914), a multicenter, phase 2, double-blind, placebo-controlled, randomized clinical trial conducted across 12 Japanese institutions, including Fukushima Medical University Hospital.² In the study, investigators enrolled 62 patients with NF2-related vestibular schwannoma. During weeks 0 through 22, participants received bevacizumab 5 mg/kg intravenously every 2 weeks or matching placebo; from weeks 24 through 46, all patients received active bevacizumab. A follow-up phase permitted up to 6 additional infusions at physician discretion.

The primary end point, proportion of patients achieving improved hearing at week 24 as assessed by maximum speech discrimination score, was achieved by 16.1% (5/31; 95% CI: 5.5–33.7) of patients in the bevacizumab arm versus 3.2% (1/31; 95% CI: 0.1–16.7) in the placebo arm. The between-group difference did not reach statistical significance (P = 0.0858); however, secondary analyses suggested trends toward hearing improvement and tumor volume reduction over the treatment period.

Adverse reactions were reported in 57.4% (35/61) of bevacizumab-treated patients; hypertension was the most common, occurring in 18.0% (11/61), consistent with the known safety profile of anti-VEGF therapy.

Clinical Context

NF2 is an autosomal dominant hereditary disorder arising from mutations in the NF2 tumor suppressor gene, with an estimated population incidence of 1 in 25,000 to 60,000 individuals. Its hallmark pathology, bilateral vestibular schwannomas, produces progressive sensorineural hearing loss, tinnitus, dizziness, and balance disturbance, most commonly with onset in the second or third decade of life. In Japan, approximately 800 patients submitted clinical registry data between 2009 and 2013. Current standard management includes watchful waiting, microsurgical resection, and stereotactic radiosurgery; however, each carries meaningful risk of hearing loss and neurological morbidity. No systemic pharmacotherapy was previously approved anywhere in the world for this condition.

REFERENCES
1. Avastin Receives Approval for Additional Indication as the World’s First Treatment for Neurofibromatosis Type 2. News release. Chugai Pharmaceutical. June 19, 2026. Accessed June 19, 2026. https://www.chugai-pharm.co.jp/english/news/detail/20260619153001_1255.html?year=2026&category=
2. Fujii M, Kobayakawa M, Saito K, et al. Rationale and Design of BeatNF2 Trial: A Clinical Trial to Assess the Efficacy and Safety of Bevacizumab in Patients with Neurofibromatosis Type 2 Related Vestibular Schwannoma. Curr Oncol. 2021;28(1):726-739. Published 2021 Jan 31. doi:10.3390/curroncol28010071
3. Screnci M, Puechmaille M, Berton Q, Khalil T, Mom T, Coll G. Bevacizumab for Vestibular Schwannomas in Neurofibromatosis Type 2: A Systematic Review of Tumor Control and Hearing Preservation. J Clin Med. 2024;13(23):7488. Published 2024 Dec 9. doi:10.3390/jcm13237488