FDA Grants Orphan Drug Designation to VBI-1901 for Glioblastoma

The FDA has granted an orphan drug designation to VBI-1901, a novel cancer immunotherapeutic vaccine candidate, as a potential therapeutic option for patients with glioblastoma.

The FDA has granted an orphan drug designation to VBI-1901, a novel cancer immunotherapeutic vaccine candidate, as a potential therapeutic option for patients with glioblastoma, according to an announcement from VBI Vaccines, Inc.1

VBI-1901 was developed using the company’s enveloped virus-like particle technology to target gB and pp65, which are both highly immunogenic cytomegalovirus (CMV) antigens. Research has shown that CMV infections are prevalent in multiple solid tumors, but they occur in more than 90% of glioblastoma cases.2 The vaccine is designed to target CMV as a foreign viral antigen, allowing patients to harness, re-stimulate, and re-focus preexisting anti-CMV immunity against CMV-positive tumors.

Data from the phase 2a trial (NCT03382977) presented during the 2022 ASCO Annual Meeting showed that patients who received VBI-1901 with granulocyte-macrophage colony-stimulating factor (GM-CSF; cohort 1; n = 10) experienced an 18-month overall survival (OS) rate of 40%. Patients who were given VBI-1901 with AS01B (cohort 2; n = 10) had an 18-month OS rate of 25%. Both approaches were noted to provide a benefit over the 12-month OS rate of 30% that is associated with the current standard of care. The median OS in cohorts 1 and 2 was 63.5 weeks and 56 weeks, respectively.

“This orphan drug designation is another significant milestone for our VBI-1901 program, and it underscores the urgency of our effort to develop meaningful new treatment options for patients with this devastating cancer,” Jeff Baxter, president and chief executive officer of VBI, stated in a press release. “As recently presented at [the 2022 ASCO Annual Meeting], we continue to see strong tumor response data and improvements in overall survival data compared with historical controls in the phase 2a study of VBI-1901. With this orphan drug status, we look forward to working closely with the FDA and clinical investigators to build on that data, advancing the potential of this program to be a valuable part of the fight against glioblastoma.”

The 2-part, multicenter, open-label, dose-expansion phase 2a trial enrolled patients with glioblastoma who experienced a first recurrence. Patients were required to have a Karnofsky performance status of at least 70%.

In cohort 1, patients received 10 µg of VBI-1901 in combination with 200 µg of GM-CSF in 0.2 mL of volume, given in 2 equal intradermal injections.3 In cohort 2, patients were administered 10 µg of VBI-1901 with AS01B (50 μg of QS-21 and 50 μg of MPL per dose) in 1.0 mL volume, given in 1 intramuscular dose.

The primary objectives of the trial were to determine safety, immunogenicity, tumor and clinical responses, and quality of life with the vaccine.

In the phase 2a trial, patients within cohort 1 had a median age of 58 years (range, 33-67); this cohort was comprised of 4 men and 6 women. In cohort 2, the median age was 65 years (range, 40-67) and included 7 men and 3 women.

Additional data showed that extended, repeat dosing of VBI-1901 with GM-CSF increased CMV-specific antibody and T-cell responses with no evidence of immunological tolerance or immune exhaustion. In 2 patients who achieved a partial response, investigators observed a dynamic boosting and loss of CD4-positive T effector memory cells in the peripheral blood. Investigators are actively looking at this as a potential immunological correlate with tumor response after treatment with VBI-1901.

A recurrent study amendment to add a control arm and increase the size of cohort 1 is expected to initiate in the third quarter of 2022.

Previously, in June 2021, the FDA granted a fast track designation to VBI-1901 for the treatment of patients with recurrent glioblastoma.4


  1. VBI Vaccines receives US FDA orphan drug designation for VBI-1901 for the treatment of glioblastoma. News release. VBI Vaccines, Inc. June 22, 2022. Accessed June 22, 2022. https://yhoo.it/3y6BG5R
  2. Wen PY, Reardon DA, Frost DA, et al. Evaluation of tumor responses and overall survival in patients with recurrent glioblastoma (GBM) from a phase IIa trial of a CMV vaccine immunotherapeutic candidate (VBI-1901). J Clin Oncol. 2022;40(suppl 16):2014. doi:10.1200/JCO.2022.40.16_suppl.2014
  3. Study to evaluate safety, tolerability, and optimal dose of candidate GBM vaccine VBI-1901 in recurrent GBM subjects. ClinicalTrials.gov. Updated October 12, 2021. Accessed June 22, 2022. https://clinicaltrials.gov/ct2/show/NCT03382977
  4. VBI Vaccines granted FDA fast track designation for VBI-1901 for the treatment of recurrent GBM. News release. VBI Vaccines, Inc. June 8, 2021. Accessed June 22, 2022. https://bit.ly/3yb0F96