VBL Therapeutics’ lead oncology product candidate, VB-111, is a targeted anti-cancer gene-based biologic agent that is positioned to treat a wide range of solid tumors with current clinical trials in recurrent Glioblastoma (rGBM), ovarian cancer and thyroid cancer.
Our pivotal Phase 3 GLOBE trial of VB-111 in rGBM is ongoing under a special protocol assessment granted by the FDA.
Glioblastoma is a brain cancer that affects approximately 10,000-12,000 newly diagnosed people each year in the United States. It is a devastating, rapidly progressing tumor, with a median time from diagnosis to the patient’s death of 12 to 15 months. In rGBM, treatment consists of both symptomatic and palliative therapies. However, with currently available therapies, glioblastoma typically remains fatal.
According to the National Cancer Institute, In 2016, it is estimated that there will be 64,300 new cases of thyroid cancer and an estimated 1,980 people will die of this disease. The American Cancer Society estimates that in 2016, about 22,280 women will be diagnosed with ovarian cancer in the United States and about 14,240 women will die from ovarian cancer.
On September 2015 at the European Cancer Conference (ECC 2015), VBL Therapeutics reported full Phase 2 data from a multi-center clinical trial of VB-111 in rGBM, meeting the primary endpoint of statistically-significant increase in overall survival.
Study data also suggest that VB-111 induces an immuno-therapeutic effect. Of the 46 patients who received VB-111, 25 patients experienced a fever post-dosing of VB-111 at least once, while 21 patients did not. Feverish patients demonstrated increased overall survival of 16 months, compared to non-feverish patients, who had a median overall survival of 8.5 months (p=0.03). This correlation between clinical efficacy and fever suggests that VB-111 induces an immune response in patients and supports a role of the immune system as part of VB-111’s mechanism of action. These findings strengthen VB-111 preclinical data, which showed an elevated immune response in tumors of VB-111-treated animals.
On June 2016, at the 2016 American Society of Clinical Oncology (ASCO) annual meeting, VBL reported new data comparing Phase 2 clinical outcomes with VB-111 with pooled data from 8 studies that investigated Avastin in recurrent glioblastoma (rGBM). In the Phase 2 VB-111 trial, the median overall survival of patients who received continuous exposure of VB-111 in combination with Avastin was 59 weeks. This is compared to 32 weeks in the pooled data from the 8 studies in the meta-analysis (p= 0.0295 Hazard Ratio 0.62, 95% CI: 0.40-0.96). Median survival ranged from 26.0 weeks to 45.7 weeks in the meta-analysis. Overall survival at 12 months for patients on continuous exposure of VB-111 was 57%, compared to 24% overall survival (range 16% – 38%) for the pooled data (p= 0.03).
In addition, at the 2016 ASCO meeting, VBL reported results from a Phase 1/2 trial of VB-111 in patients with recurrent platinum resistant ovarian cancer. The data demonstrate a median overall survival of 810 days in the VB-111 therapeutic dose arm, versus 172 days in the low dose arm, a result that was statistically significant. There was also a durable doubling in the response rate, as measured by a reduction in the CA-125 biomarker, compared to historical rates of Avastin® (bevacizumab) plus chemotherapy in ovarian cancer. Durable RECIST responses and disease stabilizations were also observed. An immunotherapeutic effect was also observed in biopsies taken from patients. The trial is conducted at Massachusetts General Hospital and Dana Farber Cancer Institute, Boston, MA.
VB-111 is conveniently administered as an IV infusion once every two months. It has been observed to be well-tolerated in >200 cancer patients and we have observed its efficacy signals in an ”all comers“ Phase 1 trial as well as in three tumor-specific Phase 2 studies. The mechanism of VB-111 combines blockade of tumor vasculature with an anti-tumor immune response. This mechanism retains activity regardless of baseline tumor mutations or the identity of the pro-angiogenic factors secreted by the tumor.
Granted composition of matter patent provides intellectual property protection for VB-111 in the US until October 2033, before any patent term extension.