Science Editor

The American Society of Clinical Oncology meeting might have been getting most of the attention, but in Boston, the Annual Meeting of the American Society for Gene Therapy also is in full swing, and among those presenting data was Gaithersburg, Md.-based VIRxSYS, Inc., which presented an update on its Phase II trial with the HIV/AIDS gene therapy VRX496 at the meeting Saturday.

The company already has published the results of a single dose of VRX496 in very late-stage patients who basically had run out of treatment options.

"This current trial moved it up into people who are responsive to current treatment options, which is the bulk of the patients in the United States," said Carl June, professor at the University of Pennsylvania, who presented the data.

The new data showed that repeated infusions of up to six times did not lead to toxicity, and also that "these cells, when you infuse them, traffic very efficiently to the GI tract," June said. A few years ago it was discovered that the bulk of HIV replication happens not in the lymph nodes, as was previously believed, but in the gastrointestinal tract.

For obvious reasons, gene therapy more commonly is associated with genetic disorders - especially immune disorders - than with infectious diseases. But the permanent nature of HIV infection makes gene therapy a viable treatment option as well as a possible prophylactic approach. The company has another vector, VRX1023, in preclinical development that is meant to work as a prophylactic HIV vaccine.

"In the long run, it could be a way to make people immune to HIV," June said. Though he stressed that any prophylactic use of gene therapy is a long way off, he also predicted that the approach would gain "more traction" given the currently grim-looking prospects for an HIV vaccine. (See BioWorld Today, Feb. 15, 2008.)

If it works, one appealing feature of a gene therapy approach is that the treatment regimen is much simpler than highly active antiretroviral therapy or HAART. Though HAART is a triumph of Western medicine, converting a once uniformly fatal disease into a chronic illness, it also is inconvenient to patients and most do not, in fact, manage to adhere to it completely, which has given rise to resistant strains of HIV.

In contrast, VRX496 likely would require what the company terms "a minimal number of infusions," June said, though he defined minimal as "an evolving concept," because it is unclear whether the lentiviral vector used by VIRxSYS can enter a subset of extremely long-lived memory T cells. If that is not the case, what June termed "maintenance infusions" might be necessary, though the regimen presumably still would be easier than HAART.

VRX496 consists of a long antisense sequence targeting the HIV envelope protein into the vector aimed at inhibiting HIV replication. When HIV replicates with a T cell, it's designed to trigger the replication of the drug, which binds to the virus and destroys it.

In what June called a surprise finding, even though it replicated previous in vitro data, treatment with VRX496 also appeared to reduce the fitness of the virus, which affected both its ability to replicate and its viral diversity within single patients. June noted that there is no clinical evidence as yet that that activity makes the virus less pathogenic, but he said that such decreased pathogenicity is a possibility, and that it ultimately might make the immune system able to control the virus.

Such immune system control of HIV "is the long-term goal," June said, but even if that goal is not achieved, VRX496 "interacts with the virus in a different way than drugs do," and could be useful as part of a combination regimen.

June said that the Phase II trial likely would be completed by the end of the year.