Cobra Biotechnology To Manufacture South African DNA Vaccine for Trials
In November, Cobra Biotechnology (Keele, UK) and the South African AIDS Vaccine Initiative (SAAVI) announced that Cobra will produce two DNA vaccines, developed by Carolyn Williamson’s research team at the University of Cape Town, for Phase I and II trials. The vaccines encode RT, Gag, Tat, Env and Nef from clade C, and will be tested in prime-boost studies (slated for late 2003 or early 2004) with an MVA vaccine carrying the same genes.
For Phase III and commercial sale, SAAVI and Cobra will combine their technologies and jointly control manufacturing rights for the vaccine in Southern Africa. Cobra has the right of refusal to produce the vaccine for all other regions of the world. The agreement also includes a possible technology transfer of manufacturing capacity from Cobra to a South African partner.
BioSyn and Partners Receive US$10 Million Microbicides Grant
BioSyn (Pennsylvania, US) and five collaborating partners have received a five-year, US $10 million grant to develop a microbicide called Cyanovirin-N (CV-N). A protein isolated from blue-green algae, CV-N has shown promise in monkeys. In a study of 26 adult female macaques, 15/18 animals pre-treated with CV-N gel showed no sign of infection after challenge with SHIV89.6P, while 8/8 controls became infected (Microbicides 2002, Abs #A-099 http://www.itg.be/micro2002/Pages/Abstracts.html). The product showed similar efficacy in a rectal challenge study, also conducted in macaques (Abs# A-0100). CV-N is thought to work as a fusion inhibitor.
Powderject Plans Phase I Therapeutic-tic DNA Vaccine Trial in 2003
In November 2002, PowderJect, a UK-based vaccine company, announced plans for a Phase I therapeutic trial of an HIV-DNA vaccine, developed as part of a collaboration with GlaxoSmithKline (GSK). The trial will combine PowderJect’s novel needle-free injection method, which delivers gold particles coated with DNA directly into skin cells, with a GSK vaccine construct. GSK will design and conduct the trial. In PowderJect’s announcement, CEO Paul Dryson referred to data from a proof-of-principle experiment that the company conducted with a prototype vaccine containing a different combination of HIV-specific plasmids than will be used in the upcoming trial. The study found that this vaccine, delivered with PowderJect’s technology and combined with antiretroviral therapy, can lead to control of viral load in immunized, SHIV-infected monkeys, according to Dryson. A PowderJect spokesperson said that these data are being prepared for publication.
Previously, PowderJect evaluated another DNA vaccine candidate and found that it protected 4/7 monkeys from a partially heterologous SIV challenge (J Virol 76:3309;2002). PowderJect is developing DNA vaccines against cancer, influenza, Hanta virus and Herpes simplex virus using its needle-free technology. It also supplies flu and smallpox vaccines delivered by traditional methods.
FDA Grants Fast Track Status to AIDSVAX
In December 2002, the US Food and Drug Administration granted Fast Track designation to the VaxGen’s two AIDS vaccine candidates—AIDSVAX B/B and AIDSVAX B/E. Fast track status allows for rapid regulatory review upon submission of an application for licensure.
VaxGen will announce results from the North American Phase III trial of AIDSVAX B/B in the first quarter of 2003. Immediately following that announcement, the Thai Data Safety and Monitoring Board (DSMB) is slated to meet and unblind the ongoing Thai Phase III trial of AIDSVAX B/E, which began 15 months after the North America/Europe study.
FDA fast track was created in 1997 to enable accelerated consideration of applications for drugs and medical devices used against life-threatening diseases. All of the antiretroviral therapies currently in use in the United States received this accelerated approval. The fast track approval process takes approximately six months from submission of the application, but this can vary by product.
VaxGen plans to submit applications to the FDA for both AIDSVAX B/B and B/E, according to company spokesman Jim Key. However, FDA approval is not required for products that will be used only outside the US, and the B/E vaccine contains gp120 protein derived from clade E HIV—the predominant subtype in Thailand, but not in circulation in the US. Thailand has its own regulatory board, which will make its determinations about AIDSVAX B/E for in-country use, should the product be deemed efficacious and an application for licensure submitted.
Epicyte Pharmaceutical and AAI Pharma to Develop Topical Monoclonal Antibodies in Plants
In September 2002, Epicyte Pharmaceutical Inc (San Diego) announced a partnership with biotech company AAI International (a division of aaiPHARMA, North Carolina) to develop a topical formulation of monoclonal antibodies (MAbs) against Herpes simplex virus type 2 (HSV-2). Epicyte produces MAbs—called Plantibodies—through a novel technology in which antibody-producing genes are inserted into crop plants such as corn and soybeans; the antibodies are then “harvested” via a multi-step process. This process is significantly cheaper than current methods for producing MAbs. For example, the company says that the annual output of 200 acres of MAb-producing corn (estimated to cost of tens of millions of US$) would equal that of a $400 million factory using an animal cell-based system.
A topical formulation of Epicyte’s anti-HSV-2 MAb, called HX-8, has shown protective efficacy in mouse studies. AAI International will develop clinical grade topical formulations for Phase I therapeutic and preventive studies of HX-8. Epicyte, which holds a broad patent covering all plant-based monoclonal antibody production (topical and systemic), is also developing anti-HIV MAbs. Phase I trials of a microbicide using these MAbs are planned for 2005.