Medical Device Daily

HIV researchers are enlisting a gene therapy product in an expanding study that's under way in southern Africa.

The newest portion of the trial is a collaborative effort between the Zambia Emory HIV Research Project, the International AIDS Vaccine Initiative (IAVI) and Targeted Genetics (Seattle) to test the safety and immunogenicity of a preventive HIV vaccine, tgAAC09. The product is Targeted Genetics' and based on HIV subtype C, the subtype of the virus most prevalent in southern Africa.

It employs a recombinant adeno-associated viral (AAV) vector to deliver select HIV genes. The naturally occurring virus is seen as advantageous because of its harmless profile; its wild type is non-pathenogenic and is not associated with causing any disease in humans. In addition, it is a simple virus with only two genes, and using recombinant AAV for transporting an HIV vaccine makes for a stable product. To date, Targeted Genetics has tested AAV vectors in more than 250 humans.

“It's a very safe delivery mechanism,” said Stacie Byars, the company's director of communications. She added that tgAAC09 is injected into study subjects' arm muscles, which contain cell types that AAV has “long-term expression” in.

Under the public-private collaboration, IAVI is funding the vaccine's development, including preclinical and clinical studies. The product is intended to protect those not infected with HIV from contracting the disease by eliciting two different types of immune responses – antibody and cell-mediated responses in T- and B-cells.

The latest trial involves a site in Zambia, a country in which a preventative HIV vaccine has never been studied, and also includes previously initiated sites in South Africa and Uganda. The center in Lusaka, Zambia, will enroll a total of 16 male and female volunteers who are in good health. The South African and Ugandan sites are recruiting 78 participants apiece.

In total, the multinational trial should take about 18 months to complete enrollment, after which Byars told Medical Device Daily's sister publication BioWorld Today that some top-line data could be available. It will test whether a second administration at six or 12 months is beneficial to immunogenicity, which is tested by measuring antibodies to antigens and CTL responses.

The African study follows positive Phase I safety data yielded from a two-year study in Belgium, Germany and India, in which volunteers received a lower-dose range of tgAAC09. IAVI estimates that there are 30 preventive HIV vaccine candidates in human trials on six continents.

HIV is one of many diseases being targeted by gene therapy developers, who have principally eyed serious and chronic ailments such as infectious diseases and cancer as appropriate indications for their technology. It continues to be aggressively explored, despite a share of negative publicity in recent years.

“The field is not dead,” said Inder Verma, a researcher at the Salk Institute for Biological Studies (La Jolla, California). He recently told members of the Congressional Biomedical Research Caucus that more than 750 clinical studies of gene therapy are under way around the world, about 10 of which are in Phase III.

Verma conceded that the “disarmingly simple” concept of gene therapy has faced challenges related to safe and efficient delivery, and that there have been few successes to date relative to the hype.

He was nonetheless optimistic about the future. Gene therapy, Verma said, “can have a major impact on human health in this century.”

There is one gene therapy product cleared for sale in the world but only in China. An oncology therapy for head-and-neck cancer, it is made by SiBiono GenTech (Shenzhen). For U.S. companies and patients, gene therapy remains in earlier research stages.

Targeted Genetics has had some success with another gene therapy product, one in clinical testing for several forms of inflammatory arthritis. Preliminary Phase I data showed that seven of nine patients who received tgAAC94, which also is delivered via an AAV vector, experienced sustained improvement in signs and symptoms eight weeks after treatment. That product delivers the DNA sequence encoding an inhibitor of TNF-alpha, TNFR:Fc, to cells within arthritic joints.

Also being used to deliver genes are retroviruses, adenoviruses and herpes simplex viruses. At Lentigen (Baltimore), a retrovirus called lentivirus is being pursued. The company was founded two years ago by CEO Boro Dropulic, who previously advanced the first lentiviral-vectored gene therapy product in clinical trials while heading another company. Today, he said, there are five gene therapy clinical studies employing lentivirus vectors. Researchers, Dropulic said, are “gravitating” to lentiviruses because of their efficiency and stability in delivering genes.

Lentigen offers on its web site a vector-building service to researchers, who can create an account and design a lentiviral vector containing a particular gene, gene-silencing sequence or both. The company then constructs and manufactures the vector.

Lentigen – which has had a single round of venture capital, the amount undisclosed – also plans to leverage its technology for its own therapeutic purposes, and Dropulic said the regulatory environment at the FDA, which once put a hold on select gene therapy trials, has been receptive.

In addition, he said the finance community has been throwing its support behind the technology, leading Dropulic to add that “gene therapy's time is coming.”