BioWorld International Correspondent
LONDON - Oxford BioMedica plc said it achieved positive interim results from Phase I/II trials of MetXia and TroVax, showing the two cancer gene therapy products were safe and prompted clinical improvements in several of those treated.
CEO Alan Kingsman told BioWorld International, “The numbers are very small, so it is certainly not proof [of efficacy] but what we have is very exciting. The fact that there were no side effects makes these landmark results for gene therapy.”
MetXia delivers the gene CYP2B6 directly to solid tumors, where it generates an enzyme that converts the prodrug cyclophosphamide into its active, cytotoxic form. In the trial in patients with advanced breast cancer, a number of tumors that were treated reduced in size.
In one patient in whom the treated tumor reduced substantially in size, a cancerous lesion that was not treated directly showed marked improvement. This was associated with indications of an antitumor immune response, and it is suggested that if administration of MetXia to one tumor can elicit an immune response that can destroy other tumors, the product could be developed as a systemic treatment for cancer. In the continuing program the immunological status of patients will be monitored to test that hypothesis.
TroVax is based on a gene for the tumor-associated antigen OBA1, which when expressed in a viral vector induces an antitumor immune response. Oxford BioMedica, based in Oxford, said in October that three of the four patients in the low-dose trial of TroVax in advanced colorectal cancer showed a clear immune response.
The latest data show that two of these three patients showed clinical improvements. In one, there was a clear correlation between increased immune response to TroVax and a significant reduction in levels of a surrogate marker, which is indicative of decreased tumor load. CT scans showed a considerable portion of the center of a large, inoperable mesenteric tumor had become necrotic. The result was evident 12 to 20 weeks after the first injection. In the second patient with a large, actively growing liver metastasis, a TroVax-induced immune response coincided with a period of disease stabilization.
“This is not scientific proof, but it is very exciting. You just don’t see these events normally in patients with this sort of advanced disease. For trials at this stage with these patients you couldn’t hope for better results,” Kingsman said.
MetXia already entered a larger Phase I/II trial in breast cancer, using material produced by an improved manufacturing process. It will involve 15 to 20 patients, and the first results are expected in a few months.
The Phase I/II trial of TroVax comprises 12 patients divided into low-, medium- and high-dose groups. The first two dose groups have been completed, and TroVax was well tolerated with no adverse effects in any patient. The company is planning the protocols for a Phase II trial of TroVax that is likely to involve about 40 patients and will have defined clinical endpoints.
Kingsman said the company has enough cash to retain the products for now. “We can fund what we have planned at the moment, so unless a cracking deal came along we’re inclined to keep them in-house.”